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Sample records for sildenafil orally disintegrating

  1. Evaluation of disintegration properties of orally rapidly disintegrating tablets using a novel disintegration tester.

    Science.gov (United States)

    Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

    2012-01-01

    This report describes a new disintegration tester that can determine not only the disintegration time of orally rapidly disintegrating tablets (ODT), but also the disintegration behavior and mechanism. Using the tester, the disintegration properties of the tablets prepared in a previous study were examined. The purpose of this study is to confirm the utility of the tester as an instrument for evaluating the disintegration properties of ODT and determine relations among time, behavior and mechanism of the disintegration. Results demonstrated that in vitro disintegration time in the tester is similar to that in the commercial disintegration tester for ODT and is highly correlated with oral disintegration time. Observations of disintegration process revealed that a difference in disintegration behavior between tablets compressed at 50-75 MPa and 100 MPa; the disintegration behavior of the tablets were designated immediate disintegrating type and gradual disintegrating type, respectively. The dynamic swelling profile and water absorption profile indicated that the disintegration mechanism of the tablets involved wicking action induced by swelling of the disintegrant; the disintegration time was closely related to the initial rates of swelling and water absorption. Furthermore, the mechanism of water absorption of tablets compressed at 50-75 MPa and 100 MPa shows anomalous diffusion and case-II transport, respectively. The shift in this mechanism is consistent with differences in disintegration time and behavior between the tablets. These findings suggest that information on disintegration properties obtained by our tester is useful for understanding of disintegration phenomena of ODT.

  2. Development of a new disintegration method for orally disintegrating tablets.

    Science.gov (United States)

    Kakutani, Ryo; Muro, Hiroyuki; Makino, Tadashi

    2010-07-01

    Recently, the focus has been on the importance of assessing the oral disintegrative properties of orally disintegrating tablets (ODTs). In particular, in the development stages and the quality control field of ODT products, a physical assessment method which easily measures oral disintegrative properties is desired. For this reason, we developed a new disintegration test method (Kyoto-model disintegration method or KYO method), which is useful to predict the oral disintegrative properties of an ODT easily, and examined the availability of the method. In the KYO method, ODT samples were classified in terms of their water permeability, and a moderate water volume was decided. Subsequently, the disintegrative properties were assessed with the newly proposed method. For 25 commercial prescription ODTs used as samples, a good correlation was shown between the results of a human sensory test by five healthy male volunteers and the results using the KYO method. Furthermore, the KYO method could evaluate time-dependent changes in ODT samples. On the other hand, no correlation was observed between the Japanese Pharmacopeia disintegration test and the human sensory test. These results suggested that the KYO method reflected the disintegration nature of the ODTs in the oral cavity, and could easily be applied to development stages and the quality control field of ODT products.

  3. Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration.

    Science.gov (United States)

    Abdelbary, G; Eouani, C; Prinderre, P; Joachim, J; Reynier, Jp; Piccerelle, Ph

    2005-03-23

    The assessment of the in vitro disintegration profile of rapidly disintegrating tablets (RDT) is very important in the evaluation and the development of new formulations of this type. So far neither the US Pharmacopoeia nor the European Pharmacopoeia has defined a specific disintegration test for RDT; currently, it is only possible to refer to the tests on dispersible or effervescent tablets for the evaluation of RDT's disintegration capacity. In the present study, we have evaluated the disintegration profile of RDT manufactured by main commercialised technologies, using the texture analyser (TA). In order to simulate as much as possible the oral disintegration of these dosage forms, a new operating structure was developed. This structure mimics the situation in the patient's mouth and provides a gradual elimination of the detached particles during the disintegration process. The obtained time-distance profiles or disintegration profiles enabled the calculation of certain quantitative values as the disintegration onset (t1) and the total disintegration time (t2). These values were used in the characterisation of the effect of test variables as the disintegration medium and temperature on the disintegration time of RDT. Moreover, the oral disintegration time of the same products was evaluated by 14 healthy volunteers. Results obtained when artificial saliva at 37 degrees C was employed as disintegration medium were used to correlate the in vitro (t2) and oral disintegration times. Excellent correlation was found and in addition, we were able to achieve a qualitative measure of the mouthfeel by comparing the thickness of the tablets and the penetration distance obtained from the disintegration profile. This method also permitted the discrimination between different RDT, where differences in the disintegration mechanism were reflected on the disintegration profile achieved for each tablet.

  4. Development and optimization of fluoxetine orally disintegrating ...

    African Journals Online (AJOL)

    Behnken design and has also been manufactured efficiently using direct compression technique. Keywords: Box-Behnken experimental design, Orally disintegrating tablets, Direct compression,. Antidepressant ... production of ODTs [4,5].

  5. Application of freeze-drying technology in manufacturing orally disintegrating films.

    Science.gov (United States)

    Liew, Kai Bin; Odeniyi, Michael Ayodele; Peh, Kok-Khiang

    2016-01-01

    Freeze drying technology has not been maximized and reported in manufacturing orally disintegrating films. The aim of this study was to explore the freeze drying technology in the formulation of sildenafil orally disintegrating films and compare the physical properties with heat-dried orally disintegrating film. Central composite design was used to investigate the effects of three factors, namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the tensile strength and disintegration time of the film. Heat-dried films had higher tensile strength than films prepared using freeze-dried method. For folding endurance, freeze-dried films showed improved endurance than heat-dried films. Moreover, films prepared using freeze-dried methods were thicker and had faster disintegration time. Formulations with higher amount of carbopol and starch showed higher tensile strength and thickness whereas formulations with higher PEG 400 content showed better flexibility. Scanning electron microscopy showed that the freeze-dried films had more porous structure compared to the heat-dried film as a result of the release of water molecule from the frozen structure when it was subjected to freeze drying process. The sildenafil film was palatable. The dissolution profiles of freeze-dried and heat-dried films were similar to Viagra® with f2 of 51.04 and 65.98, respectively.

  6. Dissolution testing of orally disintegrating tablets.

    Science.gov (United States)

    Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

    2012-07-01

    For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  7. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  8. Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

    Science.gov (United States)

    Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

    2013-01-01

    Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; pdisintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

  9. Optimized furosemide taste masked orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Mohamed Abbas Ibrahim

    2017-11-01

    Full Text Available Optimized orally disintegrating tablets (ODTs containing furosemide (FUR were prepared by direct compression method. Two factors, three levels (32 full factorial design was used to optimize the effect of taste masking agent (Eudragit E100; X1 and superdisintegarant; croscarmellose sodium (CCS; X2 on tablet properties. A composite was prepared by mixing ethanolic solution of FUR and Eudragit E100 with mannitol prior to mixing with other tablet ingredients. The prepared ODTs were characterized for their FUR content, hardness, friability and wetting time. The optimized ODT formulation (F1 was evaluated in term of palatability parameters and the in vivo disintegration. The manufactured ODTs were complying with the pharmacopeia guidelines regarding hardness, friability, weight variation and content. Eudragit E100 had a very slightly enhancing effect on tablets disintegration. However, the effects of both Eudragit E100 (X1 and CCS (X2 on ODTs disintegration time (Y1 were insignificant (p > 0.05. Moreover, X1 exhibited antagonistic effect on the dissolution after 5 and 30 min (D5 and D30, respectively, but only its effect on D30 is significant (p = 0.0004. Furthermore, the optimized ODTs formula showed good to acceptable taste in term of palatability, and in vivo disintegration time of this formula was about 10 s.

  10. [Formulation optimization of panax notoginsenoside orally fast disintegration tablets].

    Science.gov (United States)

    Wang, Zhi; Wei, Li; Chen, Ting

    2008-07-01

    To optimize the formulation of panax notoginsenoside orally fast disintegrating tablets. Mannitol, microcrystalline cellulose (PH 102) and lactose 80 were used as diluent. A polynomial regression algorithm was used to evaluate the relationship between the controlling factor, compacting pressure and diluent ratio, and disintegration time, tensile strength of tablets. Optimum formulation and process parameters could be determined by contrast the contour plot of tensile strength to that of disintegration time. The disintegration time and tensile strength of panax notoginsenoside oral disintegrating tablets were good, and the taste was satisfactory. Panax notoginsenoside oral disintegrating tablets achieve the goal of design and this method can be fairly used in formulation screening.

  11. Formulation studies for mirtazapine orally disintegrating tablets.

    Science.gov (United States)

    Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2016-01-01

    Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

  12. Design and evaluation of microwave-treated orally disintegrating tablets containing polymeric disintegrant and mannitol.

    Science.gov (United States)

    Sano, Syusuke; Iwao, Yasunori; Noguchi, Shuji; Kimura, Susumu; Itai, Shigeru

    2013-05-01

    Microwave (MW) treatment was used to develop a formulation process for the preparation of wet molded orally disintegrating tablets (ODTs) consisting of mannitol and polymeric disintegrant with improved hardness and disintegration properties. The wet molded tablets were prepared in accordance with the conventional methods and subsequently heated by MW irradiation to induce the swelling of the tablet. Croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose (L-HPC) were evaluated for their use with this technology. NBD-020, which is a grade of L-HPC, provided the better hardness and disintegration results. In addition, the crystalline forms of mannitol impacted on hardness and disintegration properties of the ODT upon MW irradiation. The effects of the disintegrant ratio, δ and β crystalline mannitol ratio, amount of water, and compression force on the ODT properties were evaluated using the design of experiment method. MW-induced swelling was enhanced by an increase in the disintegrant ratio. Although the hardness of the tablet increased following MW treatment, the disintegration time became less than that of the MW-untreated tablets as the β-mannitol ratios increased. Taken together, the results indicated that the polymeric disintegrant greatly improved the properties of the molded tablets in combination with MW treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Quantitative evaluation of the disintegration of orally rapid disintegrating tablets by X-ray computed tomography.

    Science.gov (United States)

    Otsuka, Makoto; Yamanaka, Azusa; Uchino, Tomohiro; Otsuka, Kuniko; Sadamoto, Kiyomi; Ohshima, Hiroyuki

    2012-01-01

    To measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo ODT, rapid disintegration candy (RDC) and Gaster®-D-Tablets (GAS) were used as model samples. All these ODTs were used to measure oral disintegration time (DT) in distilled water at 37±2°C by XCT. DTs were affected by the width of mesh screens, and degree to which the tablet holder vibrated from air bubbles. An in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT by the in-vivo method was significantly longer than that using the conventional tester. The experimental conditions for XCT such as the width of the mesh screen and degree of vibration were adjusted to be consistent with human DT values. Since DTs by the XCT method were almost the same as the human data, this method was able to quantitatively evaluate the rapid disintegration of ODT under the same conditions as inside the oral cavity. The DTs of four commercially available ODTs were comparatively evaluated by the XCT method, conventional tablet disintegration test and in-vivo method.

  14. A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

    Science.gov (United States)

    Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

    2016-02-20

    Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Prediction of oral disintegration time of fast disintegrating tablets using texture analyzer and computational optimization.

    Science.gov (United States)

    Szakonyi, G; Zelkó, R

    2013-05-20

    One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Oral sildenafil and inhaled iloprost in the treatment of pulmonary hypertension of the newborn.

    Science.gov (United States)

    Kahveci, Hasan; Yilmaz, Osman; Avsar, Ummu Zeynep; Ciftel, Murat; Kilic, Omer; Laloglu, Fuat; Ozturk, Kezban

    2014-12-01

    This study was performed to examine the effectiveness and safety of oral sildenafil and inhaled iloprost in term newborns with persistent pulmonary hypertension of the newborn (PPHN). Oral sildenafil and inhaled iloprost were administered to 27 and 20 neonates, respectively, for treatment of persistent pulmonary hypertension. All patients were term infants at 37 gestational weeks or older. In the sildenafil group, 14 patients had meconium aspiration syndrome, 8 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, 1 had transient tachypnea, and 1 had idiopathic PPHN. In the iloprost group, 9 patients had meconium aspiration syndrome, 7 had asphyxia (hypoxic ischemic encephalopathy stages II and III), 3 had congenital pneumonia, and 1 had transient tachypnea. Sildenafil citrate was administered via an oral feeding tube. Iloprost was administered endotracheally to patients on mechanical ventilation using a jet nebulizer. Iloprost appeared to be more effective than sildenafil in the treatment of PPHN with regard to time to adequate clinical response, ventilatory parameters, duration of drug administration, duration of mechanical ventilation, duration of return to normal values of respiratory failure indices, use of MgSO4 as a second vasodilator and requirement for support with inotropic agents. We observed no side effects on blood pressure or homeostasis in any of the patients in the iloprost group. Systemic hypotension was significantly elevated in the sildenafil group. Four and three infants died of PPHN in the sildenafil and iloprost groups, respectively. Pulmonary systolic arterial pressure decreased to normal levels in the remaining 40 patients, and they were discharged from hospital. We suggested that inhaled iloprost may be a safe and effective treatment choice in newborn infants with persistent pulmonary hypertension. In cases where treatment with inhaled iloprost, ECMO or INO is not possible, oral sildenafil can be an

  17. [Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

    Science.gov (United States)

    Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

    2018-01-01

     For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

  18. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

    Science.gov (United States)

    Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

    2017-07-04

    Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start

  19. Preparation and evaluation of diclofenac sodium orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Iancu Valeriu

    2016-06-01

    Full Text Available Orally disintegrating tablets (ODTs are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets batches by direct compression method at different compression forces 10 kN (F1 and 20 kN (F2 and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w. The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time. Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.

  20. Orally Disintegrating Tablets: A Review | Hirani | Tropical Journal of ...

    African Journals Online (AJOL)

    Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. Over the past three decades, orally disintegrating tablets (ODTs) have gained considerable attention as a preferred ...

  1. Development and Evaluation of Orally Disintegrating Tablets of ...

    African Journals Online (AJOL)

    designed and manufactured by direct compression method, using microcrystalline (Avicel PH-102), mannitol ... batch (FOB-01) reflected the successful development of new formulation of orally disintegrating ... investigate the product variables that influence product quality. .... thickness was high but was within limits of ± 5 %.

  2. Magnetic Resonance Imaging to Visualize Disintegration of Oral Formulations.

    Science.gov (United States)

    Curley, Louise; Hinton, Jordan; Marjoribanks, Cameron; Mirjalili, Ali; Kennedy, Julia; Svirskis, Darren

    2017-03-01

    This article demonstrates that magnetic resonance imaging can visualize the disintegration of a variety of paracetamol containing oral formulations in an in vitro setting and in vivo in the human stomach. The different formulations had unique disintegration profiles which could be imaged both in vitro and in vivo. No special formulation approaches or other contrast agents were required. These data demonstrate the potential for further use of magnetic resonance imaging to investigate and understand the disintegration behavior of different formulation types in vivo, and could potentially be used as a teaching tool in pharmaceutical and medical curricula. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  4. Formulation and in vitro characterization of novel sildenafil citrate-loaded polyvinyl alcohol-polyethylene glycol graft copolymer-based orally dissolving films.

    Science.gov (United States)

    Xu, Li-Li; Shi, Li-Li; Cao, Qing-Ri; Xu, Wei-Juan; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

    2014-10-01

    This work was aimed to develop novel sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer (Kollicoat(®) IR)-based orally dissolving films (ODFs) using a solvent casting method. Formulation factors such as plasticizers and disintegrants were optimized on the basis of characteristics of blank ODFs. The SC-loaded ODF with a loading capacity up to 6.25mg in an area of 6 cm(2) was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The physicochemical properties of drug-loaded ODF were also investigated using the scanning electron microscope (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of Kollicoat(®) IR, sodium alginate (ALG-Na) and glycerol (10:2:1.5, w/w) had a remarkably short disintegration time of about 20s. The SC-loaded ODF showed a delayed disintegration time (about 25s), but exhibited improved mechanical properties when compared to the blank ODF. SC was homogeneously dispersed throughout the ODF and the crystalline form of drug had been partly changed, existing strong hydrogen bonding between the drug and carriers. The Kollicoat(®) IR/ALG-Na based ODFs containing SC might be an alternative to conventional tablet for the treatment of male erectile dysfunction. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Formulation and evaluation of orally disintegrating clopidogrel tablets

    Directory of Open Access Journals (Sweden)

    Gamal Mohamed Mahrous

    Full Text Available ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC. DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

  6. Evaluation of co-processed excipients used for direct compression of orally disintegrating tablets (ODT) using novel disintegration apparatus.

    Science.gov (United States)

    Brniak, Witold; Jachowicz, Renata; Krupa, Anna; Skorka, Tomasz; Niwinski, Krzysztof

    2013-01-01

    The compendial method of evaluation of orodispersible tablets (ODT) is the same disintegration test as for conventional tablets. Since it does not reflect the disintegration process in the oral cavity, alternative methods are proposed that are more related to in vivo conditions, e.g. modified dissolution paddle apparatus, texture analyzer, rotating shaft apparatus, CCD camera application, or wetting time and water absorption ratio measurement. In this study, three different co-processed excipients for direct compression of orally disintegrating tablets were compared (Ludiflash, Pharmaburst, F-Melt). The properties of the prepared tablets such as tensile strength, friability, wetting time and water absorption ratio were evaluated. Disintegration time was measured using the pharmacopoeial method and the novel apparatus constructed by the authors. The apparatus was based on the idea of Narazaki et al., however it has been modified. Magnetic resonance imaging (MRI) was applied for the analysis of the disintegration mechanism of prepared tablets. The research has shown the significant effect of excipients, compression force, temperature, volume and kind of medium on the disintegration process. The novel apparatus features better correlation of disintegration time with in vivo results (R(2) = 0.9999) than the compendial method (R(2) = 0.5788), and presents additional information on the disintegration process, e.g. swelling properties.

  7. Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.

    Science.gov (United States)

    Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

    2015-01-01

    The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.

  8. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs).

    Science.gov (United States)

    Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

    2015-09-01

    Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800-900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p disintegration time determination is eligible and scientifically justified.

  9. Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

    Science.gov (United States)

    Siden, Rivka; Wolf, Matthew

    2013-06-01

    The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

  10. Evaluation of spray and freeze dried excipient bases containing disintegration accelerators for the formulation of metoclopramide orally disintegrating tablets

    International Nuclear Information System (INIS)

    Alanazi, Fars K.

    2007-01-01

    Orally disintegrating tablets (ODT) are gaining attractiveness over conventional tablets especially for patients having difficulty in swallowing such as pediatric, geriatric, bedridden and disable patients. ODT technologies render the tablets disintegrate in the mouth without chewing or additional water intake. So far there have been many patents for ODT, but only few publications are dealing with this dosage form. The aim of the present study was to formulate metoclopramide in ODT with sufficient mechanical strength and fast disintegration from bases prepared by both spray (SD) and freeze drying (FD) techniques. Different disintegration accelerators (DA) were utilized to prepare proper ODT using various super-disintegrants (Ac-Di-Sol, Kollidon and Sodium Starch glycolate), a volatilizing solvent (ethanol) and an amino acid (glycine). Metoclopramide, an antiemetic medication, was used a model drug in the formulated ODT. It was noted that the disintegration of ODT depends on utilization of DA in both SD and FD techniques to prepare tablet bases for ODT and so many other factors such as drying processes. The good disintegration property of the prepared tablets was related to the excellent wettability of the ingredients after being subjected to the drying processes. Results also showed that the addition of DA to the tablet bases before drying process results in lengthening of the disintegration time in comparison to their addition to the tablet bases after the drying process. Those findings be utilized for many drugs and they may be considered versatile in their applications. Also, the disintegration of the ODT in the buccal cavity may favor fast absorption via the mucus membrane in the oral cavity. (author)

  11. Lecithin, gelatin and hydrolyzed collagen orally disintegrating films: functional properties.

    Science.gov (United States)

    Borges, J G; Silva, A G; Cervi-Bitencourt, C M; Vanin, F M; Carvalho, R A

    2016-05-01

    Orally disintegrating films (ODFs) can transport natural active compounds such as ethanol extract of propolis (EEP). This paper aimed to investigate the effect of lecithin on different gelatin and hydrolyzed collagen (HC) polymeric matrices with addition of EEP. ODFs were prepared by casting technique and were characterized (color parameters, water content, mechanical properties, microstructure, disintegration time (DT), infrared spectroscopy (FTIR), contact angle (CA), swelling degree and total phenolic content). The mechanical properties were influenced by HC. The microstructure demonstrated increased porosity and roughness in films with EEP, and the addition of lecithin resulted in an increase in the number of pores. Lecithin-gelatin and lecithin-EEP-gelatin interactions were observed by FTIR. The addition of HC and EEP reduced the DT and CA, and HC and lecithin reduced the swelling capacity. However, the swelling capacity was not affected by presence of EEP. The addition of lecithin to gelatin and HC ODFs may improve the incorporation and the oral transport of active compounds such as EEP. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Changes in Retinal and Choroidal Vascular Blood Flow after Oral Sildenafil: An Optical Coherence Tomography Angiography Study

    Directory of Open Access Journals (Sweden)

    David Berrones

    2017-01-01

    Full Text Available Purpose. To describe changes in the retina and choroidal flow by optical coherence tomography angiography (OCT-A after a single dose of oral sildenafil. Method. A case-control study. Patients in the study group received 50 mg of oral sildenafil. Patients in the control group received a sham pill. Retinal and choroidal images were obtained at baseline (before pill ingestion and 1 hour after ingestion. Central macular and choroidal thickness, choroidal and outer retina flow, and the retinal and choroidal vascular density were compared using a Mann-Whitney U test. Results. Twenty eyes were enrolled into the study group and 10 eyes in the control group. There was a significant difference in central choroidal thickness and outer retina blood flow between groups after 1 hour of sildenafil ingestion (p<0.01. There were no differences in central macular thickness, choroidal flow, and retinal vascular density among groups. Conclusions. A single dose of oral sildenafil increases choroidal thickness, probably due to sildenafil-induced vasodilation.

  13. Characterization of low cost orally disintegrating film (ODF

    Directory of Open Access Journals (Sweden)

    Riana Jordao Barrozo Heinemann

    Full Text Available Abstract Orally disintegrating films (ODF produced with a hydrophilic polymers are a thin and flexible material, wich disintegrate in contact with saliva and can vehicule bioactive materials. The aim of this study was to develop and characterize ODF formulation with potential to act as a carrier for different bioactives compounds prepared with low cost polymers. Gelatin (G, starch (S, carboxymethyl cellulose (CMC and their blends (G:S, CMC:S, CMC:G, and CMC:S:G were prepared by casting technique with sorbitol as a plasticizer. The formulations were characterized in terms of visual aspects, FTIR, SEM, mechanical characteristics, hygroscopicity, dissolution (in vitro and in vivo and swelling index. FTIR analysis revealed that no interaction between polymers in ODF was observed. By SEM, it was possible to observe differences on surfaces by different polymers. ODF made with CMC and CMC:G presented higher water absorption (P<0.05 and higher swelling index probably due to the higher water affinity by CMC. Formulations with G, CMC:G and CMC:S:G presented the highest values of tensile strength (P<0.05. ODF prepared with S alone presented the highest disintegration time, the others formulations showed in vitro dissolution ranging from 5.22 to 8.50 min, while in vivo dissolution time ranged from 2.15 to 3.38 min. By the formulations made with G and blend of G:S and CMC:S:G it is possible to develop a ODF of low cost with desired characteristics being an alternative vehicle to deliver functional compounds for continuous use.

  14. Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test.

    Science.gov (United States)

    Harada, Tsutomu; Narazaki, Ryuichi; Nagira, Shinsuke; Ohwaki, Takayuki; Aoki, Shigeru; Iwamoto, Kiyoshi

    2006-08-01

    The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.

  15. Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

    Science.gov (United States)

    Al-Gousous, Jozef; Langguth, Peter

    2015-09-01

    Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

    Science.gov (United States)

    Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

    2016-01-01

    We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (pginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

  17. Development and evaluation of ofloxacin orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Badrinath Pralhadrao Mohite

    2012-06-01

    Full Text Available Bitter taste of ofloxacin, a broad spectrum bactericidal agent, is masked and orally disintegrating tablets were formulated. The bitter taste is masked by forming complex between drug and weak cation exchange resins, Tulsion 335 and Indion 204. Effect of pH and drug:resin ratio on the drug loading was studied. Maximum drug loading was observed at pH 6. Ratio of 1:2 of drug:resin masked almost complete bitterness of ofloxacin. Formation of complexes was confirmed by IR spectroscopy. Physical characterization of taste masked complexes was carried out. Present work envisages the taste masking of ofloxacin and development of orally disintegrating tablets. The effect of pH and resin quantities on drug loading were studied to find the optimum conditions of drug loading for complete taste masking. Effect of superdisintegrants like sodium starch glycolate, croscarmellose sodium and polyplasdone XL at varying level on physical parameters of compressed tablets was also assessed. The formulations containing 5 % w/w polyplasdone XL showed about 90 % of drug release within 5 minutes. No significant differences were observed in the physical parameters of resinates as well as tablets prepared from Tulsion 335 and Indion 204.O gosto amargo de ofloxacina, agente bactericida de largo espectro, é mascarado e formularam-se comprimidos dispersíveis. O sabor amargo é mascarado pela formação de complexo entre o fármaco e resinas de troca catiônica fraca, Tulsion 335 e Indion 204. Efeito do pH e da proporção fármaco: resina sobre a carga de fármaco foi estudada. Carga de fármaco máxima foi observada em pH 6. Proporção 1:2 do fármaco: resina mascarou quase completamente o gosto amargo de ofloxacina. A formação de complexos foi confirmada por espectroscopia no IV. Caracterização física dos complexos de sabor mascarado foi realizada. O presente trabalho preconiza o mascaramento do gosto de ofloxacina e desenvolvimento decomprimidos por via oral, se

  18. Gelatin/hydroxypropyl methylcellulose matrices — Polymer interactions approach for oral disintegrating films

    Energy Technology Data Exchange (ETDEWEB)

    Tedesco, Marcela P., E-mail: marcela.tedesco@usp.br; Monaco-Lourenço, Carla A., E-mail: carla.monaco@usp.br; Carvalho, Rosemary A., E-mail: rosecarvalho@usp.br

    2016-12-01

    Oral disintegrating film represents an optimal alternative for delivery system of active compounds. The choice of film-forming polymer is the first step in the development of oral disintegrating films and the knowledge of molecular interactions in this matrix is fundamental to advance in this area. Therefore, this study aimed to characterize gelatin and hydroxypropyl methylcellulose (HPMC) films and their blends as matrices of oral disintegrating films. The films were produced by casting technique and were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, mechanical properties, contact angle, time disintegration and bioadhesive strength. Differential scanning calorimetry showed that enthalpy of fusion and melting temperatures of the blends films were lower than those of the gelatin film, which may be associated with the lack of intra-chain interactions also observed in the Fourier transform infrared spectra. In blends, a less compact cross-section structure was observed in scanning electron microscopy images compared with isolated polymer films. The addition of HPMC increased the elongation, hydrophilicity and in vitro bioadhesive force and decreased in vitro disintegration time, important properties in the development of oral disintegrating films. Although the mixture of the polymers showed no synergistic behavior, this study may contribute to the development of new applications for polymeric matrices in the pharmaceutical industry. - Highlights: • Effect of gelatin/HPMC blend on oral disintegrating films properties. • Intramolecular interaction of films was evaluated. • Mixtures of the polymers provoked reductions in intra-chain interactions. • HPMC content affects hydrophilic of oral disintegrating films.

  19. Gelatin/hydroxypropyl methylcellulose matrices — Polymer interactions approach for oral disintegrating films

    International Nuclear Information System (INIS)

    Tedesco, Marcela P.; Monaco-Lourenço, Carla A.; Carvalho, Rosemary A.

    2016-01-01

    Oral disintegrating film represents an optimal alternative for delivery system of active compounds. The choice of film-forming polymer is the first step in the development of oral disintegrating films and the knowledge of molecular interactions in this matrix is fundamental to advance in this area. Therefore, this study aimed to characterize gelatin and hydroxypropyl methylcellulose (HPMC) films and their blends as matrices of oral disintegrating films. The films were produced by casting technique and were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, mechanical properties, contact angle, time disintegration and bioadhesive strength. Differential scanning calorimetry showed that enthalpy of fusion and melting temperatures of the blends films were lower than those of the gelatin film, which may be associated with the lack of intra-chain interactions also observed in the Fourier transform infrared spectra. In blends, a less compact cross-section structure was observed in scanning electron microscopy images compared with isolated polymer films. The addition of HPMC increased the elongation, hydrophilicity and in vitro bioadhesive force and decreased in vitro disintegration time, important properties in the development of oral disintegrating films. Although the mixture of the polymers showed no synergistic behavior, this study may contribute to the development of new applications for polymeric matrices in the pharmaceutical industry. - Highlights: • Effect of gelatin/HPMC blend on oral disintegrating films properties. • Intramolecular interaction of films was evaluated. • Mixtures of the polymers provoked reductions in intra-chain interactions. • HPMC content affects hydrophilic of oral disintegrating films.

  20. Development of Oral Fast-Disintegrating Levothyroxine Films for ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research ... The films were evaluated for disintegration time, in vitro drug release, physical appearance, thickness, ... film is suitable for levothyroxine in the management of hypothyroidism in pediatrics.

  1. Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.

    Science.gov (United States)

    Shanmugam, Srinivasan; Kim, Young-Hun; Park, Jeong-Hee; Im, Ho Taek; Sohn, Young Taek; Kim, Kyeong Soo; Kim, Yong-Il; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon; Woo, Jong Soo

    2014-06-01

    The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.

  2. Formulation and Characterization of Acetaminophen Nanoparticles in Orally Disintegrating Films

    Science.gov (United States)

    AI-Nemrawi, Nusaiba K.

    The purpose of this study is to prepare acetaminophen loaded nanoparticles to be cast directly, while still in the emulsion form, into Orally Disintegrating Films (ODF). By casting the nanoparticles in the films, we expected to keep the particles in a stable form where the nanoparticles would be away from each other to prevent their aggregation. Once the films are applied on the buccal mucosa, they are supposed to dissolve within seconds, releasing the nanoparticles. Then the nanoparticles could be directly absorbed through the mucosa to the blood stream and deliver acetaminophen there. The oral cavity mucosa is one of the most attractive sites for systemic drug delivery due to its high permeability and blood supply. Furthermore, it is robust and shows short recovery times after stress or damage, and the drug bypasses first pass effect and avoids presystemic elimination in the GI tract. Nanoencapsulation increases drug efficacy, specificity, tolerability and therapeutic index. These Nanocapsules have several advantages in the protection of premature degradation and interaction with the biological environment, enhancement of absorption into a selected tissue, bioavailability, retention time and improvement of intracellular penetration. The most important characteristics of nanoparticles are their size, encapsulation efficiency (EE), zeta potential (surface charge), and the drug release profiles. Unfortunately, nanoparticles tend to precipitate or aggregate into larger particles within a short time after preparation or during storage. Some solutions for this problem were mentioned in literature including lyophilization and spray drying. These methods are usually expensive and give partial solutions that might have secondary problems; such as low re-dispersion efficacy of the lyophilized NPs. Furthermore, most of the formulations of NPs are invasive or topical. Few formulas are available to be given orally. Fast disintegrating films (ODFs) are rapidly gaining interest

  3. A new formulation for orally disintegrating tablets using a suspension spray-coating method.

    Science.gov (United States)

    Okuda, Y; Irisawa, Y; Okimoto, K; Osawa, T; Yamashita, S

    2009-12-01

    The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants.

  4. Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach.

    Science.gov (United States)

    Sankar, V; Ramakrishna, B; Devi, P Shalini; Karthik, S

    2012-11-01

    Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets.

  5. Orally disintegrating olanzapine and potential differences in treatment-emergent weight gain

    NARCIS (Netherlands)

    Karagianis, Jamie; Hoffmann, Vicki Poole; Arranz, Belen; Treuer, Tamás; Maguire, Gerald A.; de Haan, Lieuwe; Chawla, Bharat

    2008-01-01

    Several papers and communications have reported possible weight reduction or less weight gain when patients start or switch to orally disintegrating olanzapine, as contrasted with standard oral olanzapine tablets. In this paper, the current literature is reviewed and hypothesized mechanisms of

  6. Taste-masking assessment of orally disintegrating tablets and lyophilisates with cetirizine dihydrochloride microparticles

    Directory of Open Access Journals (Sweden)

    Aleksandra Amelian

    2017-12-01

    Full Text Available Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral

  7. Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

    Science.gov (United States)

    Tsertsvadze, Alexander; Yazdi, Fatemeh; Fink, Howard A; MacDonald, Roderick; Wilt, Timothy J; Bella, Anthony J; Ansari, Mohammed T; Garritty, Chantelle; Soares-Weiser, Karla; Daniel, Raymond; Sampson, Margaret; Moher, David

    2009-10-01

    To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

  8. Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users.

    Science.gov (United States)

    Bjarnadottir, G D; Johannsson, M; Magnusson, A; Rafnar, B O; Sigurdsson, E; Steingrimsson, S; Asgrimsson, V; Snorradottir, I; Bragadottir, H; Haraldsson, H M

    2017-09-01

    Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (pusers and non-users. To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Preparation, characterization and ex vivo evaluation of an orally disintegrating film formulation containing pyrazinamide

    CSIR Research Space (South Africa)

    Adeleke, Oluwatoyin A

    2015-10-01

    Full Text Available Vivo Evaluation of an Orally Disintegrating Film Formulation Containing Pyrazinamide O. A. Adeleke 1, P-C. Tsai 2, B. B. Michniak-Kohn 2 1 Council for Scientific and Industrial Research, 2 Rutgers - The State University of New Jersey Purpose...

  10. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Science.gov (United States)

    Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

    2017-01-01

    A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

  11. A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

    Science.gov (United States)

    Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

    2018-08-01

    The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

  12. Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

    Science.gov (United States)

    Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

    2013-09-01

    The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

  13. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability

    International Nuclear Information System (INIS)

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95 ± 2.80% drug release in 60 min was observed in comparison to 24.85 ± 2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66 ± 1.52 s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD–ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. - Highlights: • β-cyclodextrin–eslicarbazepine acetate complex developed with enhanced solubility. • Formulated Orally disintegrating tablets (ODT) disintegrated within 30 s. • Bioavailability from ODT was 2 times higher than marketed tablets. • Onset of action for ODT was also faster than marketed tablets. • Formulated ODT would aid epileptic patients incapable of swallowing tablets.

  14. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika, E-mail: dr_krutikasawant@yahoo.co.in

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95 ± 2.80% drug release in 60 min was observed in comparison to 24.85 ± 2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66 ± 1.52 s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD–ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. - Highlights: • β-cyclodextrin–eslicarbazepine acetate complex developed with enhanced solubility. • Formulated Orally disintegrating tablets (ODT) disintegrated within 30 s. • Bioavailability from ODT was 2 times higher than marketed tablets. • Onset of action for ODT was also faster than marketed tablets. • Formulated ODT would aid epileptic patients incapable of swallowing tablets.

  15. Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

    Science.gov (United States)

    El-Say, Khalid M; Ahmed, Tarek A; Abdelbary, Maged F; Ali, Bahaa E; Aljaeid, Bader M; Zidan, Ahmed S

    2015-12-01

    This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for pre- and post-compression characteristics. The prepared OD-mini-tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

  16. Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics

    Directory of Open Access Journals (Sweden)

    El-Say Khalid M.

    2015-12-01

    Full Text Available This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1, swelling pressure of the superdisintegrant (X2, and the surface area of Aerosil as a glidant (X3. Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2 and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

  17. Development and characterization of orally-disintegrating films for propolis delivery

    Directory of Open Access Journals (Sweden)

    Josiane Gonçalves Borges

    2013-02-01

    Full Text Available This study aimed at evaluating the effect of different concentrations of hydrolyzed collagen (HC on the properties of an orally disintegrating film containing propolis ethanol extract (PEE as an active component. The films were evaluated in terms of total phenols, mechanical properties, solubility, contact angle, disintegration time, and microstructure. The films were prepared by casting with 2 g of protein mass (gelatin and HC, 30 g of sorbitol/100 g of protein mass, and 100 g of PEE/100 g of protein mass. HC was incorporated at concentrations of 0, 10, 20, and 30 g/100 g of protein mass. It was found that increased concentrations of HC reduced tensile strength and increased elongation; however, all films showed plastic behavior. An increase in solubility at 25 ºC, a reduction in the contact angle, and disintegration time were also observed. Thus, higher concentrations of collagen led to more hydrophilic and more soluble polymeric matrices that showed shorter dissolution time, favoring the use of these materials as carriers for active compounds to be delivered in the oral cavity.

  18. Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2012-02-01

    Full Text Available William Montgomery1, Tamas Treuer2, Jamie Karagianis3, Haya Ascher-Svanum4, Gavan Harrison51Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 2Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 5Asia-Pacific Medical Communications, Eli Lilly and Company, Sydney, AustraliaAbstract: Orally disintegrating olanzapine (ODO is a rapid-dissolving formulation of olanzapine which disintegrates in saliva almost immediately, developed as a convenient and adherence-enhancing alternative to the standard olanzapine-coated tablet (SOT. Clinical studies, which form the basis of this review, have shown ODO and SOT to have similar efficacy and tolerability profiles. However, ODO appears to have a number of advantages over SOT in terms of adherence, patient preference, and reduction in nursing burden. Overall, the existing clinical data suggests that compared to SOT, ODO is not only well-suited for difficult-to-treat, agitated, and/or nonadherent patients but, due to its potential ability to improve adherence and greater patient preference, may also be an appropriate formulation for the majority of patients for which olanzapine is the antipsychotic of choice.Keywords: orodispersible formulation, orally disintegrating, olanzapine, atypical antipsychotics, patient adherence, preference, schizophrenia, bipolar disorder

  19. Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.

    Science.gov (United States)

    Tayebi, Hoda; Mortazavi, Seyed Alireza

    2011-01-01

    Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

  20. A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study

    NARCIS (Netherlands)

    Karagianis, J.; Grossman, L.; Landry, J.; Reed, V. A.; de Haan, L.; Maguire, G. A.; Hoffmann, V. P.; Milev, R.

    2009-01-01

    BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine

  1. Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering.

    Science.gov (United States)

    Wang, Chenguang; Hu, Shenye; Sun, Changquan Calvin

    2017-10-02

    A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

  2. Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

    Science.gov (United States)

    Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

    2017-01-01

    Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

  3. Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Radicioni M

    2017-04-01

    Full Text Available Milko Radicioni,1 Chiara Castiglioni,1 Andrea Giori,2 Irma Cupone,3 Valeria Frangione,4 Stefano Rovati4 1CROSS Research S.A., Phase I Unit, Arzo, Switzerland; 2IBSA Farmaceutici Italia, Lodi, Italy; 3Bouty S.p.A., Strada Padana Superiore, Cassina De’ Pecchi, Italy; 4IBSA Institut Biochimique S.A., Pambio-Noranco, Switzerland Abstract: A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra® after single-dose administration to 53 healthy male volunteers (aged 18–51 years in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg

  4. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  5. Weight loss during therapy with olanzapine orally disintegrating tablets: two case reports.

    Science.gov (United States)

    Kozumplik, Oliver; Uzun, Suzana; Jakovljević, Miro

    2009-03-01

    The aim of this article is to report weight loss in patients with schizophrenia after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In the first case report, the patient was switched to olanzapine ODT in daily dosage of 20 mg, while in the second case report, the patient was switched to olanzapine ODT in daily dosage of 15 mg, and weight loss was similar (14 kg vs. 15 kg). Switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained during 12 months in both case reports. Further controlled clinical investigations are necessary to evaluate change in weight during treatment with olanzapine ODT, and to improve our understanding of this change.

  6. Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

    Science.gov (United States)

    Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

    2010-06-01

    The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

  7. Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets.

    Directory of Open Access Journals (Sweden)

    Ali Al-Khattawi

    Full Text Available The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT excipients microcrystalline cellulose (MCC and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair. Moreover, surface topography images (100 nm2-10 µm2 and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale.

  8. Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

    Science.gov (United States)

    Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

    2014-01-01

    The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

  9. Formulation strategy and evaluation of nanocrystal piroxicam orally disintegrating tablets manufacturing by freeze-drying.

    Science.gov (United States)

    Lai, Francesco; Pini, Elena; Corrias, Francesco; Perricci, Jacopo; Manconi, Maria; Fadda, Anna Maria; Sinico, Chiara

    2014-06-05

    Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poor water solubility and consequently by a low oral bioavailability. In this work, different nanocrystal orally disintegrating tablets (ODT) were prepared to enhance piroxicam dissolution rate and saturation solubility. PRX nanocrystals were prepared by means of high pressure homogenization technique using poloxamer 188 as stabilizer. Three different ODTs were prepared with the same nanosuspension using different excipients in order to study their effect on the PRX dissolution properties. PRX nanocrystal size and zeta potential were determined by photon correlation spectroscopy. Additional characterization of PRX nanocrystal ODT was carried out by infrared spectroscopy, X-ray powder diffractometry, differential scanning calorimetry. Dissolution study was performed in distilled water (pH 5.5) and compared with PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a PRX commercial ODT. All PRX nanocrystal ODT formulations showed a higher drug dissolution rate than coarse PRX ODT. PRX nanocrystal ODT prepared using gelatin or croscarmellose as excipient showed a higher PRX dissolution rate compared with the commercial formulation and ODT prepared using xanthan gum. Overall results confirmed that improved PRX dissolution rate is due to the increased surface-to-volume ratio due to the nanosized drug particle but also revealed the important role of different excipients used. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Zhao J

    2014-02-01

    Full Text Available Jingping Zhao,1 Jianjun Ou,1 Haibo Xue,2 Li Liu,2 William Montgomery,3 Tamas Treuer4 1Mental Health Institute of The Second Xiangya Hospital, Hunan Province Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Lilly Suzhou Pharmaceutical Co, Ltd, Jiangsu, People's Republic of China; 3Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 4Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary Abstract: The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. Keywords: orally disintegrating, olanzapine, Chinese, schizophrenia, patients

  11. Reduction in the volume of water for ingesting orally disintegrating tablets of solifenacin (Vesicare® OD), and the clinical disintegration time of Vesicare® OD after unit-dose packaging.

    Science.gov (United States)

    Uchida, Shinya; Yoshita, Tomohiro; Namiki, Noriyuki

    2013-03-25

    This study aimed to determine the amount of water required for ingesting an orally disintegrating tablet (ODT) of solifenacin (Vesicare(®), VES) and VES conventional tablets (VES-CT). We measured the disintegration time of VES-ODT in the oral cavity (clinical disintegration time) before and after unit-dose packaging. Thirty healthy volunteers participated in this randomized crossover trial. The participants were asked to drink water during the intake placebos of VES and after the disintegration of placebos of VES-ODT in their oral cavity. The amounts of water required for ingesting placebos of VES-CT and of VES-ODT were 42.8±27.0 mL and 20.0±23.7 mL, respectively, which indicated that the amount of water required for ingesting ODTs was significantly lesser than that for ingesting CTs. Furthermore, 5 (16.7%) participants did not require water for ingesting the ODTs. Clinical disintegration time of VES-ODT was 21.4s in 10 healthy volunteers. This clinical disintegration time did not change significantly after unit-dose packaging or subsequent storage for 56 days. This study showed that the amount of water required for ingesting VES-ODT is lower than that for ingesting VES-CT. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  12. User of ordered mixtures to obtain high dose homogeneity in mini-tablets : studies of orally disintegrating systems for children

    OpenAIRE

    Løding, Fredrik Sandberg

    2011-01-01

    Studies have shown that homogeneity is higher in ordered mixtures compared to random mixtures. Based on this ordered mixtures should be particularly suitable for the preparation of mini-tablets. The overall aim of the study was to compare the homogeneity of ordered mixtures prepared using different particle size of carrier particles, and test their suitability for preparation of mini-tablets. The mini-tablets are intended for use as orally disintegrating systems (ODT) for children...

  13. Enhancement of Solubility of Lamotrigine by Solid Dispersion and Development of Orally Disintegrating Tablets Using 32 Full Factorial Design

    Directory of Open Access Journals (Sweden)

    Jatinderpal Singh

    2015-01-01

    Full Text Available Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs of lamotrigine using β-cyclodextrin and PVP-K30 as polymers for the preparation of solid dispersion which help in enhancement of aqueous solubility of this BCS CLASS-II drug and sodium starch glycolate (SSG and crospovidone as a superdisintegrating agent, to reduce disintegration time. The ODTs were prepared by direct compression method. Nine formulations were developed with different ratios of superdisintegrating agents. All the formulations were evaluated for disintegration time, weight variation, hardness, friability, drug content uniformity, wetting time, and in vitro drug release study. In vitro drug release study was performed using United States Pharmacopoeia (USP type 2 dissolution test apparatus employing paddle stirrer at 50 rpm using 900 mL of 0.1 N HCl maintained at 37°C ± 0.5°C as the dissolution medium. On the basis of evaluation parameters formulations were prepared using β-CD 1 : 1 solid dispersion. Then 32 full factorial design was applied using SSG and crospovidone in different ratios suggested by using design expert 8.0.7.1 and optimized formulation was prepared using amount of SSG and crospovidone as suggested by the software. The optimized formulation prepared had disintegrating time of 15 s, wetting time of 24 s, and % friability of 0.55.

  14. Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

    Science.gov (United States)

    Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

    2017-03-01

    A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

  15. Formulation, preparation, and evaluation of novel orally disintegrating tablets containing taste-masked naproxen sodium granules and naratriptan hydrochloride.

    Science.gov (United States)

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-04-01

    The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design.

    Science.gov (United States)

    Patro, Chandra Sekhar; Sahu, Prafulla Kumar

    2017-01-01

    Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs) by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS) and natural Hibiscus rosa-sinensis mucilage (HRM) as disintegrants in the formulation. Central composite design (CCD) was applied to optimize the influence of three levels each of CCS ( X 1 ) and HRM ( X 2 ) concentrations (independent variables) for investigated responses: disintegration time (DT) ( Y 1 ), % friability ( F ) ( Y 2 ), and % cumulative drug release (DR) ( Y 3 ) (dependent variables). This face-centered second-order model's reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses' sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR) and thermograms from Differential Scanning Calorimetry (DSC) demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

  17. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar Patro

    2017-01-01

    Full Text Available Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS and natural Hibiscus rosa-sinensis mucilage (HRM as disintegrants in the formulation. Central composite design (CCD was applied to optimize the influence of three levels each of CCS (X1 and HRM (X2 concentrations (independent variables for investigated responses: disintegration time (DT (Y1, % friability (F (Y2, and % cumulative drug release (DR (Y3 (dependent variables. This face-centered second-order model’s reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses’ sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR and thermograms from Differential Scanning Calorimetry (DSC demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

  18. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Li FQ

    2011-04-01

    Full Text Available Feng-Qian Li1, Cheng Yan2, Juan Bi1, Wei-Lin Lv3, Rui-Rui Ji3, Xu Chen1, Jia-Can Su3, Jin-Hong Hu31Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaAbstract: Scopolamine hydrobromide (SH-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w and loading capacity of 20% (w/w were achieved for the microparticles, which ranged from 2 µm to 8 µm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics.Keywords: scopolamine hydrobromide, chitosan, nanoparticles-in-microparticles system, spray-drying, orally disintegrating tablets

  19. Comparative Study Between Different Ready-Made Orally Disintegrating Platforms for the Formulation of Sumatriptan Succinate Sublingual Tablets.

    Science.gov (United States)

    Tayel, Saadya A; El Nabarawi, Mohamed A; Amin, Maha M; AbouGhaly, Mohamed H H

    2017-02-01

    Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol®, chitosan, or Polyox®-were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

  20. Sildenafil dilates ophthalmic artery in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Akeel AMH Zwain

    2013-08-01

    Full Text Available Background: Conflicting reports exist on the effect of sildenafil on ophthalmic artery blood flow; many visual disturbances due to vascular insult were reported with the use of sildenafil in diabetic patients like nonarteritic ischemic optic neuropathy. Objectives: The present work aimed to investigate whether sildenafil modulates ophthalmic artery vasoreactivity in patients with type 2 diabetes mellitus. Literature reports on this aspect are lacking. Methods: A total of 35 male subjects were enrolled in this study, 18 with type 2 diabetes mellitus matched with 17 normal individuals. Ophthalmic artery was insonated through a transorbital window using colored Doppler equipment with transcranial Doppler facility. Ophthalmic artery reactivity was assessed using breath holding/hyperventilation test, before and after giving 50 mg oral sildenafil. Results: It was found that in both normal subjects and diabetic patients, sildenafil increased baseline control of mean flow velocity of ophthalmic artery significantly (p 0.05 after sildenafil, in normal and diabetic groups. There was a significant increase of resistive index of ophthalmic artery flow in diabetic patients compared with that of normal subject (p < 0.05. Sildenafil decreased resistive index of ophthalmic artery flow significantly only in diabetic patients (p < 0.05. Conclusion: Sildenafil increased MFVopa, but had no significant effect on vasoreactivity of ophthalmic artery; sildenafil decreased resistive index only in type 2 diabetic patients.

  1. Estudo da circulação retrobulbar e do campo visual após dose única oral de citrato de sildenafil (Viagra® The effects of a single dose of sildenafil citrate (Viagra® on the retrobulbar circulation and visual field

    Directory of Open Access Journals (Sweden)

    Alessandra Kurahashi

    2001-08-01

    Full Text Available Objetivo: Estudar os efeitos na circulação retrobulbar e no campo visual de uma dose oral única de 100 mg de citrato de sildenafil (Viagra®. Métodos: Um estudo duplo-mascarado e controlado por placebo foi realizado em 10 voluntários do sexo masculino, com idade média de 27,7 + 5,68 anos. O olho direito de cada voluntário foi submetido aos exames de Doppler colorido de órbita e análise de campo visual por meio de perimetria computadorizada (Humphrey, programa 30-2, estratégia "Full Threshold" em 3 ocasiões: "baseline", 1 hora após placebo e 1 hora após 100 mg de sildenafil via oral. No campo visual, analisaram-se o limiar foveal e o "mean deviation" (MD nas 3 ocasiões. No Doppler colorido, medimos a velocidade sistólica máxima (VSM, a velocidade diastólica final (VDF e o índice de resistência (IR da artéria central da retina (ACR e da artéria oftálmica (AO nas 3 ocasiões. Resultados: A administração do sildenafil não alterou significativamente o limiar foveal e o "mean deviation" em relação ao "baseline" e ao placebo. Houve um aumento significativo da velocidade sistólica máxima e velocidade diastólica final na artéria oftálmica após a administração do citrato de sildenafil (pPurpose: To analyze the effects of 100 mg of sildenafil citrate (Viagra® on the retrobulbar circulation and visual field. Methods: A double masked, placebo controlled study was conducted in 10 males with a mean age of 27.7 + 5.68 years. The right eye of each volunteer underwent orbital color Doppler imaging and automated perimetry (Humphrey, program 30-2, Full-Threshold Strategy at 3 occasions: baseline, 1 hour after placebo and 1 hour after 100 mg of sildenafil. The foveal threshold and the mean deviation (MD were analyzed by automated perimetry on the three occasions. Color Doppler imaging allowed the measurement of the peak systolic velocity (PSV, end diastolic velocity (EDV and Pourcelot index (PI in the central retinal artery and

  2. Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

    Science.gov (United States)

    Mazumder, Sonal; Pavurala, Naresh; Manda, Prashanth; Xu, Xiaoming; Cruz, Celia N; Krishnaiah, Yellela S R

    2017-07-15

    The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film. A Definitive Screening Design of Experiments (DoE) was used to identify and classify the critical formulation and process variables impacting critical quality attributes (CQA). A total of 14 laboratory-scale DoE formulations were prepared and evaluated for mechanical properties (%elongation at break, yield stress, Young's modulus, folding endurance) and other CQA (dry thickness, disintegration time, dissolution rate, moisture content, moisture uptake, drug assay and drug content uniformity). The main factors affecting mechanical properties were plasticizer to film former ratio and drying temperature. Dissolution rate was found to be sensitive to air flow rate during drying and plasticizer to film former ratio. Data were analyzed for elucidating interactions between different variables, rank ordering the critical materials attributes (CMA) and critical process parameters (CPP), and for providing a predictive model for the process. Results suggested that plasticizer to film former ratio and process controls on drying are critical to manufacture LMT ODF with the desired CQA. Published by Elsevier B.V.

  3. Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.

    Science.gov (United States)

    Ito, Yoshitaka; Maeda, Atsushi; Kondo, Hiromu; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-09-10

    The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Science.gov (United States)

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

  5. Oral sildenafil (Viagra™ in male erectile dysfunction: use, efficacy and safety profile in an unselected cohort presenting to a British district general hospital.

    Directory of Open Access Journals (Sweden)

    Boustead Gregory

    2002-04-01

    Full Text Available Abstract Introduction Sildenafil (Viagra® is one of the drugs used in the first line therapy of male erectile dysfunction (MED. We have recorded outcomes, adverse events and acceptability of Sildenafil (Viagra therapy in an unselected group of men presenting with ED to a British district general hospital. Methods In this prospective observational study, 147 men with ED were seen since Oct 1999. Study patients were reviewed at 4, 12 and 52 weeks. All the patients filled the International Index of Erectile Function (IIEF questionnaire and were asked about their willingness to pay (WTP for treatment. Results All suitable men accepted Viagra as first line therapy. 91% of our patients found sildenafil treatment successful. 80% of these patients were willing to continue with sildenafil therapy. Side effect profile of sildenafil was different in this study with much higher incidence of headache, dyspepsia, flushing and abnormal vision. 92% of men with ED expect to be treated by the NHS. Of those men eligible for treatment in the NHS, 30% qualify under the clinical categories and 18% under the 'distress' category. Only 55% of those with cardiovascular risk factors qualify for NHS treatment. Conclusions Sildenafil is widely accepted as first line therapy among British men with ED and has a success rate of 91%. Nearly half of men with ED qualify for NHS treatment. Nearly half of those with vascular risk factors do not qualify for NHS treatment. Most men with ED could possibly be managed in primary care.

  6. Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

    Science.gov (United States)

    Eltony, Sohair A; Abdelhameed, Sally Y

    2017-04-01

    Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.

    Science.gov (United States)

    Liew, Kai Bin; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2015-04-01

    Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

  8. The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors.

    Science.gov (United States)

    Lorberboym, M; Mena, I; Wainstein, J; Boaz, M; Lampl, Y

    2010-06-01

    Sildenafil citrate is widely used for erectile dysfunction. The present study examined the short-term effects of sildenafil administration in individuals with cerebrovascular risk factors, including patients with a history of stroke. Twenty-five consecutive male patients with erectile dysfunction and vascular risk factors were included in the study. A perfusion brain SPECT study was performed at baseline and 1 h after the oral administration of sildenafil. Associations between any of the risk factors and the perfusion scores were not detected, with the exception of stroke. Stroke patients showed significantly more areas with diminished perfusion after sildenafil administration compared to baseline. In patients with diabetes or hypertension, a dose of 50 mg sildenafil does not appear to produce detrimental effects on cerebral blood flow. However, patients with a history of stroke may be at increased risk of hemodynamic impairment after the use of sildenafil.

  9. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

    Science.gov (United States)

    Mishra, Saurabh M; Rohera, Bhagwan D

    2017-11-01

    The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

  10. Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

    Science.gov (United States)

    Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

  11. Sildenafil-associated hepatoxicity: a review of the literature.

    Science.gov (United States)

    Graziano, S; Montana, A; Zaami, S; Rotolo, M C; Minutillo, A; Busardò, F P; Marinelli, E

    2017-03-01

    Sildenafil citrate (Viagra®) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.

  12. Sildenafil normalizes bowel transit in preclinical models of constipation.

    Directory of Open Access Journals (Sweden)

    Sarah K Sharman

    Full Text Available Guanylyl cyclase-C (GC-C agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC and irritable bowel syndrome with constipation (IBS-C. Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.

  13. Should the patient with coronary artery disease use sildenafil?

    Science.gov (United States)

    Cheitlin, Melvin D

    2003-01-01

    Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in life will be markedly improved by their ability to engage in sexual activity.

  14. Development of a novel and simple method to evaluate disintegration of rapidly disintegrating tablets.

    Science.gov (United States)

    Hoashi, Yohei; Tozuka, Yuichi; Takeuchi, Hirofumi

    2013-01-01

    The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g. Properties of RDTs, such as the pattern of their disintegrating process, can be assessed by verifying the load. These findings confirmed that our proposed method for an in vitro disintegration test apparatus is an excellent one for estimating disintegration time and the disintegration profile of RDTs.

  15. Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

    Directory of Open Access Journals (Sweden)

    Balarini Camille M

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS and nitric oxide (NO. Sildenafil, a selective phosphodiesterase-5 (PDE5 inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/− mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage were compared to the untreated apoE−/− and the wild-type (WT mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor or apocynin (NADPH oxidase inhibitor. In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous

  16. Sildenafil in the Treatment of SSRI-Induced Sexual Dysfunction: A Pilot Study

    OpenAIRE

    Damis, Marina; Patel, Yatin; Simpson, George M.

    1999-01-01

    Background: Sexual dysfunction is a well-documented side effect of selective serotonin reuptake inhibitors (SSRIs). Commonly reported side effects include erectile impotence, anorgasmia, ejaculatory delay, pain, loss of sensation, and decreased pleasure. Early reports of the reversal of sexual dysfunction after using sildenafil in male and female patients receiving various types and dosages of SSRIs are promising and prompted this study. Our aim was to evaluate the effects of oral sildenafil ...

  17. Long-term weight loss observed with olanzapine orally disintegrating tablets in overweight patients with chronic schizophrenia. A 1 year open-label, prospective trial.

    Science.gov (United States)

    Chawla, Bharat; Luxton-Andrew, Heather

    2008-04-01

    To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04). This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months. 2008 John Wiley & Sons, Ltd.

  18. [Psychosocial disintegration].

    Science.gov (United States)

    Köhler, S

    1994-08-01

    Among the patients referred for rehabilitation in the latter half of their working life, many are notable due to considerable discrepancies between their objectively ascertainable performance and its subjectively perceived decline. In these cases, the "substantial threat to earning capacity" cannot be explained by measurable organ deficiencies. Similarly, treatment efforts focussed solely at improved somatic functioning remain inefficient in terms of stabilization of earning capacity, because they do not bring about changes in the cause of subjective performance deterioration. The author in these circumstances assumes the presence of an independent syndrome, called "psychosocial disintegration". He describes the full picture of this disease entity, and suggests causal mechanisms as well as potential for remedial intervention. On account of the considerable social dimension of the disorder outlined, early identification of these gradually developing changes as well as qualified care of the insurants are indispensable. All those involved in treatment and care of the patients or working in some branch of the social security system should be familiar with this psychosocial disintegration syndrome in order to avoid the guidance and counselling mistakes that are frequently the case. As rehabilitation is impossible in case of inhibiting personal attitudes of an insurant, it is advisable to verify the individual's readiness for rehabilitation and/or to strengthen it by appropriate measures before engaging in costly in-patient service provision. If the needed motivation is to be achieved during participation in a rehabilitation measure, extended service provision will invariably be required.

  19. Review of Disintegrants and the Disintegration Phenomena.

    Science.gov (United States)

    Desai, Parind Mahendrakumar; Liew, Celine Valeria; Heng, Paul Wan Sia

    2016-09-01

    Disintegrant is one of the most important components in a typical tablet dosage form. It is responsible for ensuring the break-up of the tablet matrix upon ingestion. Disintegrants act by different mechanisms, and a number of factors may affect their performance. It is important for formulators to understand how disintegrants function so as to be able to judiciously use disintegrants to develop optimized formulations. If the formulator is required to implement the quality by design paradigm while developing a tablet formulation, it would be important to determine the impact of component ranges and process variations on tablet performance and of particular importance, tablet disintegration. Thus, a better understanding of the mechanisms of disintegrants and the tablet disintegration processes can be critical to product design success. This review aims to provide an overview of tablet disintegrants and the disintegration processes with particular focus on the factors affecting the functionalities of disintegrants. An updated compendium of different techniques employed to evaluate disintegrant action and measure disintegration time is also provided. The objective of this review is to assemble the knowledge about disintegrants and the measurement of tablet disintegratability so that the information provided could be of help to tablet formulation development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Gautam V Ramani

    2010-05-01

    Full Text Available Gautam V Ramani, Myung H ParkUniversity of Maryland, Baltimore, MD, USAAbstract: Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH. The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. Keywords: sildenafil, pulmonary arterial hypertension, phosphodiesterase type 5 inhibitor

  1. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

  2. Black lung persistent pulmonary hypertension of the newborn. Saudi experience with sildenafil and nitric oxide.

    Science.gov (United States)

    Alnemri, AbdulRahman M

    2017-01-01

    To determine the clinical presentation, risk factors, diagnosis, and treatment outcome of Saudi infants with black lung persistent pulmonary hypertension of the newborn (PPHN). Methods: This is a retrospective review of all neonates with PPHN presented to the Armed Force Hospital Southern Region, Kingdom of Saudi Arabia from January 2012 to December 2014. Results: Ten term and near term infants presented with PPHN were included. Maternal diabetes and Down syndrome were the most common identified risk factors for PPHN in the study group. Nine infants were treated with oral sildenafil and did not require mechanical ventilation. Only one infant required mechanical ventilation and inhaled nitric oxide in addition to oral sildenafil. Conclusion: Most of the patients in this cohort with PPHN had risk factors, they did not require mechanical ventilation and responded well to oral sildenafil.

  3. Black lung persistent pulmonary hypertension of the newborn. Saudi experience with sildenafil and nitric oxide

    Directory of Open Access Journals (Sweden)

    AbdulRahman M. Alnemri

    2017-01-01

    Full Text Available Objectives: To determine the clinical presentation, risk factors, diagnosis, and treatment outcome of Saudi infants with black lung persistent pulmonary hypertension of the newborn (PPHN. Methods: This is a retrospective review of all neonates with PPHN presented to the Armed Force Hospital Southern Region, Kingdom of Saudi Arabia from January 2012 to December 2014. Results: Ten term and near term infants presented with PPHN were included. Maternal diabetes and Down syndrome were the most common identified risk factors for PPHN in the study group. Nine infants were treated with oral sildenafil and did not require mechanical ventilation. Only one infant required mechanical ventilation and inhaled nitric oxide in addition to oral sildenafil. Conclusion: Most of the patients in this cohort with PPHN had risk factors, they did not require mechanical ventilation and responded well to oral sildenafil.

  4. Effects of sildenafil and/or muscle derived stem cells on myocardial infarction

    Directory of Open Access Journals (Sweden)

    Wang Judy SC

    2012-08-01

    Full Text Available Abstract Background Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. Methods MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1 untreated; 2 oral sildenafil 3 mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3 saline; 4 rat MDSC (106 cells; 5 as #4, with sildenafil as in #2. Before surgery, and at 1 and 4 weeks, the left ventricle ejection fraction (LVEF was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. Results As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Conclusions Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5.

  5. A systematic review assessing the economic impact of sildenafil citrate (Viagra) in the treatment of erectile dysfunction.

    Science.gov (United States)

    Martin, Amber L; Huelin, Rachel; Wilson, David; Foster, Talia S; Mould, Joaquin F

    2013-05-01

    Sildenafil was the first oral phosphodiesterase type 5 (PDE5) inhibitor introduced as primary therapy for erectile dysfunction (ED). In the 7 years following its market launch, sildenafil was prescribed by more than 750,000 physicians to more than 23 million men worldwide. To date, few studies have evaluated the economic impact of sildenafil in treating ED. To evaluate the cost-effectiveness and impact of sildenafil on health care costs for patients with ED in multiple countries. Economic outcomes including cost, cost-effectiveness, cost of illness, cost consequence, resource use, productivity, work loss, and willingness to pay (WTP) were investigated. Using keywords related to economic outcomes and sildenafil, we systematically searched literature published between July 2001 and July 2011 using MEDLINE and EMBASE. Included articles pertained to costs, WTP, and economic evaluations. In the last 10 years, 12 studies assessed economic outcomes associated with sildenafil for ED. Most studies were conducted in the United States and the United Kingdom, with one study identified in Canada and one from Mexico. Six studies evaluated cost of illness, cost consequence, or cost of care, and four studies evaluated WTP or drug pricing by country in the United States and the United Kingdom. In the United States and the United Kingdom, costs to health care systems have increased with demand for treatment. Cost analyses suggested that sildenafil would lower direct costs compared with other PDE5 inhibitors. U.S. and U.K. studies found that patients exhibited WTP for sildenafil. The two cost-effectiveness models we identified examined ED sub-groups, those with spinal cord injury and those with diabetes or hypertension. These models indicated favorable cost-effectiveness profiles for sildenafil compared with other active-treatment options in both Mexico and Canada. The relative value of sildenafil vs. surgically implanted prosthetic devices and other PDE5 inhibitors, is underscored

  6. Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

    Science.gov (United States)

    Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

    2007-12-01

    Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

  7. Development and characterization of orally-disintegrating films for propolis delivery Desenvolvimento e caracterização de filmes de desintegração para liberação oral de própolis

    Directory of Open Access Journals (Sweden)

    Josiane Gonçalves Borges

    2013-02-01

    Full Text Available This study aimed at evaluating the effect of different concentrations of hydrolyzed collagen (HC on the properties of an orally disintegrating film containing propolis ethanol extract (PEE as an active component. The films were evaluated in terms of total phenols, mechanical properties, solubility, contact angle, disintegration time, and microstructure. The films were prepared by casting with 2 g of protein mass (gelatin and HC, 30 g of sorbitol/100 g of protein mass, and 100 g of PEE/100 g of protein mass. HC was incorporated at concentrations of 0, 10, 20, and 30 g/100 g of protein mass. It was found that increased concentrations of HC reduced tensile strength and increased elongation; however, all films showed plastic behavior. An increase in solubility at 25 ºC, a reduction in the contact angle, and disintegration time were also observed. Thus, higher concentrations of collagen led to more hydrophilic and more soluble polymeric matrices that showed shorter dissolution time, favoring the use of these materials as carriers for active compounds to be delivered in the oral cavity.Este trabalho teve como objetivo avaliar o efeito de diferentes concentrações de colágeno hidrolisado nas propriedades de filmes de desintegração oral contendo extrato etanólico de própolis como componente ativo. Os filmes foram avaliados em relação aos fenóis totais, propriedade mecânica, solubilidade, ângulo de contato, tempo de desintegração e microestrutura. Os filmes foram produzidos por "casting" com concentrações de 2 g de massa proteica (gelatina e colágeno hidrolisado, 30 g de sorbitol/100 g de massa proteica e 100 g de extrato fenólico de própolis/100 g de massa proteica. Colágeno hidrolisado foi incorporado nas concentrações de 0, 10, 20 e 30 g/100 g de massa proteica. Verificou-se que o aumento da concentração de colágeno hidrolisado provocou redução na tensão de ruptura e aumento da elongação, entretanto todos os filmes

  8. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

  9. A comparative study of aripiprazole orally disintegrating tablets and Haloperidol treatment for tic disorders%阿立哌唑口腔崩解片与氟哌啶醇治疗抽动障碍的对比研究

    Institute of Scientific and Technical Information of China (English)

    郑庆梅; 李耀东; 邓良华; 谭助英

    2015-01-01

    Objective To evaluate the efficacy and tolerability of Aripiprazole orally disintegrating tablets and Haloperidol treatment in children with tic disorders. Method 61 Tourette patients were randomly divided into two groups,treatment with Aripiprazole orally disintegra-ting tablets and Haloperidol for 8 weeks. Before treatment and in the second,fourth and eighth weekend,YGTSSS and TESS were used to eval-uate efficacy and side effects. Results In the 2nd,4th and 8th weekend vocal tic,total damage and total scores of YGTSS both in Aripiprazole group and Haloperidol group significantly decreased. But in the second weekend motor tics score worse than haloperidol. In terms of safety,side effects and tolerance of Aripiprazole orally disintegrating tablets was better. Conclusion Aripiprazole orally disintegrating tabletsis effective for treatment of tic disorder,and high safety.%目的:比较阿立哌唑口腔崩解片和氟哌啶醇治疗抽动障碍的临床疗效和安全性。方法:将符合抽动障碍的61例儿童随机分为两组,分别接受氟哌啶醇和阿立哌唑口腔崩解片治疗,并在治疗2周、4周及8周末分别进行耶鲁综合抽动严重程度量表(Yale Global Tic Severity Scale,YGTSS)、不良反应量表(treatment emergent symptomscale,TESS)评估其疗效和安全性。结果:阿立哌唑口腔崩解片与氟哌啶醇组在治疗的2、4、8周末在YGTSS量表发声抽动、整体损害和YGTSS总分疗效评分上均无明显差异,在2周末运动抽动疗效评分上较氟哌啶醇差;在安全性方面,阿立哌唑口腔崩解片不良反应更小,耐受性更好。结论:阿立哌唑口腔崩解片在治疗抽动障碍上有显著的疗效,和更好地安全性。

  10. Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

    Science.gov (United States)

    Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

    2010-09-01

    Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright

  11. Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy after Ingestion of Sildenafil for Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Tarantini

    2012-01-01

    Full Text Available Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION after ingestion of Sildenafil citrate (Viagra for erectile dysfunction. Methods. Observational case report. Results. A 60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours after his third consecutive 50 mg daily Sildenafil ingestion. A diagnosis of bilateral NAION was made and he was treated for three days with methylprednisolone 1 g/d intravenously, followed by oral prednisone 75 mg/d. Final visual acuity was 20/50 right eye (OD and 20/20 left eye (OS. He had preexisting diabetes. Conclusion. This is the first reported case of simultaneous bilateral NAION occurred in a diabetic patient early after Sildenafil intake. Patients with predisposing conditions such as diabetes have to be warned against the use of PDE inhibitors.

  12. Effect of sildenafil citrate on secondary healing in full thickness skin defects in experiment.

    Science.gov (United States)

    Cakmak, E; Karasoy Yesilada, A; Sevim, K Z; Sumer, O; Tatlidede, H S; Sakiz, D

    2014-01-01

    An acceleration of the wound healing process expedites chronic wound patient's return to normal social environments significantly. Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phosphodiesterase- 5 inhibitor has been shown to be a potent stimulator of angiogenesis through upregulation of cGMP. In our study, sildenafil was administered orally as a cost-effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity. Randomly selected 72 Wistar-Albino rats were divided into the two groups, 36 rats in each group. Control group (n =36) was divided further into a secondary healing group consisting of 9 rats and a pathology group consisting of 27 rats (pathology group 1: 9 rats, 4th and 7th day of wound healing, pathology group 2: 9 rats, 10th and 14th day of wound healing, pathology group 3: 9 rats, 21st and 28th day of wound healing. Experimental group consisted of 36 rats which received sildenafil citrate (Viagra® Pfizer, Germany) for secondary wound healing to proceed. The average wound healing period in the control group was 17.89 days and in the sildenafil citrate administered group 14.56 days. The difference of the epithelialisation on full thickness defects were more prominent on days 5 and 11 postoperatively. In the sildenafil citrate applied group, on the 7th day, the defect was 25% smaller and on the 13th day, the defect contracted by 38%. In conclusion, we believe that sildenafil citrate administered orally is a cost- effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity (Tab. 4, Fig. 7, Ref. 34).

  13. Evaluation of synthesized cross linked polyvinyl alcohol as potential disintegrant.

    Science.gov (United States)

    Patel, Ashok R; Vavia, Pradeep R

    2010-01-01

    The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant. Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use. Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity. By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.

  14. USE OF SILDENAFIL (VIAGRA® FOR ERECTILE DYSFUNCTION IN DIALYSIS PATIENTS – OUR FIRST EXPERIENCE

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    Bojan Vujkovac

    2002-01-01

    Full Text Available Background. Male patients with end stage renal disease often report erectile dysfunction, which is very common especially in younger males. Impotence is reported to exceed 50% in male chronic renal failure patients, and is present in 65% of such patients undergoing hemodialysis. Numerous etiological factors have been reported as possible cause for sexual dysfunction. Sildenafil (Viagra®, a potent specific inhibitor of cGMP phosphodiesterase, was used in this case study to improve erectile dysfunction in dialysis male patients.Methods and results. During 12 weeks we treated 4 dialysis patients. 2 patients were treated with peritoneal dialysis and 2 patients were in the program of chronic hemodialysis. All patients were in the program of dialysis for more than 24 months, and reported erectile dysfunction and impotence after they had started with dialysis treatment. Sildenafil was used in the treatment. The dosage schedule for sildenafil was 50mg/ week orally for 2 weeks followed by 100 mg/week for the next 10 weeks if there was no effect on initial dosage. Efficacy of treatment was evaluated by means of the International Index of Erectile Dysfunction. All 4 patients reported no significant effect on initial dose. With higher dose of sildenafil treatment was overwhelmingly successful, with reported prolonged improvement of erectile dysfunction for 42 to 72 hours. Side effects were present only in 1 patient who had severe headaches after higher dose. No patients experienced priapism.Conclusions. There have been only few reports in the literature on the use of sildenafil in dialysis patients. Our small case study suggests that sildenafil could be successfully and safely used for treatment of erectile dysfunction also in dialysis patients. A large trial would be necessary to confirm the efficacy of the drug for this specific group of patients.

  15. Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

    Science.gov (United States)

    Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

    2018-01-01

    Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

  16. Sildenafil increases cerebrovascular reactivity: a transcranial Doppler study.

    Science.gov (United States)

    Diomedi, M; Sallustio, F; Rizzato, B; Ferrante, F; Leone, G; Spera, E; Scarfini, M; Bernardi, G

    2005-09-27

    The authors performed a double-blind, placebo-controlled study in 28 patients to evaluate the effects of sildenafil on cerebral hemodynamics. A significant improvement of cerebrovascular reactivity, without any modification of other variables, was recorded 1 hour after the administration of 50 mg sildenafil. Further investigations are needed to evaluate whether cerebrovascular reactivity improvement could contribute to triggering sildenafil-induced migraine.

  17. Applicability of two automated disintegration apparatuses for rapidly disintegrating (mini)tablets.

    Science.gov (United States)

    Sieber, Daniel; Lazzari, Alessia; Quodbach, Julian; Pein, Miriam

    2017-03-01

    Orally disintegrating (mini)tablets (OD(M)Ts) are of interest in the field of pharmaceutics. Their orodispersible character is defined by the disintegration time, which is measured with a basket apparatus according to the European Pharmacopoeia. This method, however, lacks applicability for ODTs and especially ODMTs. New disintegration apparatuses have been described in literature, but a qualification to assess the applicability has not been described. A qualification procedure for two automated disintegration apparatuses, OD-mate and Hermes apparatus, is introduced. Aspects of the operational qualification as well as precision and accuracy regarding a performance qualification were evaluated for both apparatuses analog to the ICH guideline Q2. While the OQ study is performed separately for each apparatus, accuracy and precision were performed following the same protocol for both testers. Small RSDs (16.9% OD-mate; 15.2% Hermes compared to 32.3% for the pharmacopeial method) were found despite very fast disintegration times (1.5 s for both apparatuses). By comparing these RSDs to practical examples, the authors propose threshold values for repeatability depending on the mean disintegration time. Obtained results from the qualification were used to assess the applicability of both apparatuses.

  18. Efficacies of Papaverine and Sildenafil in the Treatment of Erectile Dysfunction in Early-Stage Paraplegic Men

    Science.gov (United States)

    Yildiz, Necmettin; Gokkaya, Nilufer Kutay Ordu; Koseoglu, Fusun; Gokkaya, Serkan; Comert, Didem

    2011-01-01

    The aim of the study was to determine which vasoactive agent was more efficacious for erectile dysfunction (ED), intracavernosal papaverine or oral sildenafil, in paraplegic men within the first year after injury by using a penile color Doppler ultrasound as a quantitative imaging method and to determine the association between responses to these…

  19. Sildenafil no tratamento da hipertensão pulmonar após cirurgia cardíaca Sildenafil for pulmonary hypertension treatment after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Maria Regina Bentlin

    2005-04-01

    Full Text Available OBJETIVO: Relatar o uso do Sildenafil no tratamento da hipertensão pulmonar em recém-nascido após cirurgia cardíaca. DESCRIÇÃO: Recém-nascido de termo, feminino, com diagnóstico de dupla via de saída de ventrículo direito, hipoplasia de pulmonar e comunicação interventricular subaórtica, foi submetido à cirurgia de Blalock na primeira semana de vida. No pós-operatório, evoluiu com hipertensão pulmonar e hipoxemia persistente, não-responsiva ao óxido nítrico, porém com melhora da oxigenação após infusão endovenosa contínua de prostaglandina E1. Depois de várias tentativas malsucedidas de retirada da prostaglandina E1, optou-se pela introdução do Sildenafil via oral. Houve queda da resistência vascular pulmonar, com conseqüente melhora na oxigenação e, 48 horas após, foi possível suspender a infusão de prostaglandina E1. COMENTÁRIOS: O Sildenafil pode ser alternativa terapêutica na hipertensão pulmonar, especialmente quando não houver resposta à terapia convencional.OBJECTIVE: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. DESCRIPTION: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. COMMENTS: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy.

  20. The blue pill (sildenafil and its descendants: an overview

    Directory of Open Access Journals (Sweden)

    Krzanowski Tomasz

    2017-09-01

    Full Text Available An increasing number of men around the world suffer from erectile dysfunction (ED. Indeed, according to the sexuality study conducted by Professor Izdebski, 1 out of 10 men in Poland suffers from ED. The problem is found among men of any age, however, 60% of all patients are between 40 and 60 years old, thus in their prime, and who still want to fully enjoy life. Not only do the effects of ED affect a man, but they have influence on his relationship and partner as well. In spite of a growing awareness within society, the problem remains perceived as embarrassing, which leads patients to treat themselves on their own, delaying a visit to their doctors. Meanwhile, in many cases, ED may be the first symptom of more serious diseases, such as diabetes, or result from the sideeffects of applied drugs. A breakthrough in the oral medication treatment of ED was observed when a new phosphodiesterase type 5 inhibitor (PDE-5-inhibitor - sildenafil citrate (Viagra® - was introduced. Nowadays, 5 active substances from this group are being applied. The current medical guidelines recommend PDE-5 inhibitors as the firstline therapy for most men with ED, irrespective of the cause and severity of the disease. Recently, sildenafil at the dose of 25 mg came into the market without prescription. This paper presents an overview and update of the PDE-5 inhibitors.

  1. Evaluation of the Effects of Sildenafil Citrate (Viagra) on Vertebral Artery Blood Flow in Patients with Vertebro-Basilar Insufficiency

    International Nuclear Information System (INIS)

    Bozgeyik, Zulkif; Berilgen, Sait; Ozdemir, Huseyin; Ogur, Erkin; Tekatas, Aslan

    2008-01-01

    To investigate the effects of sildenafil citrate (Viagra) on the vertebral artery blood flow of patients with vertebro-basilar insufficiency (VBI) using color duplex sonography (CDS). The study included 21 patients with VBI (aged 31-76; mean 61.0 ± 10.5 yrs). We administered a 50 mg oral dose of sildenafil citrate to all patients. Next, we measured the peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistive index (RI), pulsatility index (PI), diameter, area, and flow volume (FV) of vertebral arteries using CDS before the administration of sildenafil citrate; 45 minutes after, and 75 minutes after administration. Statistical testing was performed using SPSS for windows version 11.0. The statistical test used to determine the outcome of the analysis was the repeated measures analysis of variance (ANOVA) test. Compared to the baseline values, the vertebral artery diameter, area, and FV increased significantly following the administration of sildenafil citrate. The diameter, area and FV increased from 3.39 mm at 45 minutes to 3.64 mm at 75 minutes, 9.43 cm 2 to 10.80 cm 2 at 45 minutes and 10.81 cm 2 at 75 minutes, as well as from 0.07 L/min at baseline to 0.09 L/min at 45 minutes and unchanged at 75 minutes, respectively. Sildenafil citrate elicited a significant effect on vertebral artery diameter, area and FVs

  2. Evaluation of the effects of sildenafil citrate (viagra) on vertebral artery blood flow in patients with vertebro-basilar insufficiency.

    Science.gov (United States)

    Bozgeyik, Zulkif; Berilgen, Sait; Ozdemir, Huseyin; Tekatas, Aslan; Ogur, Erkin

    2008-01-01

    To investigate the effects of sildenafil citrate (Viagra) on the vertebral artery blood flow of patients with vertebro-basilar insufficiency (VBI) using color duplex sonography (CDS). The study included 21 patients with VBI (aged 31-76; mean 61.0 +/- 10.5 yrs). We administered a 50 mg oral dose of sildenafil citrate to all patients. Next, we measured the peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistive index (RI), pulsatility index (PI), diameter, area, and flow volume (FV) of vertebral arteries using CDS before the administration of sildenafil citrate; 45 minutes after, and 75 minutes after administration. Statistical testing was performed using SPSS for windows version 11.0. The statistical test used to determine the outcome of the analysis was the repeated measures analysis of variance (ANOVA) test. Compared to the baseline values, the vertebral artery diameter, area, and FV increased significantly following the administration of sildenafil citrate. The diameter, area and FV increased from 3.39 mm at 45 minutes to 3.64 mm at 75 minutes, 9.43 cm(2) to 10.80 cm(2) at 45 minutes and 10.81 cm(2) at 75 minutes, as well as from 0.07 L/min at baseline to 0.09 L/min at 45 minutes and unchanged at 75 minutes, respectively. Sildenafil citrate elicited a significant effect on vertebral artery diameter, area and FVs.

  3. Evaluation of the Effects of Sildenafil Citrate (Viagra) on Vertebral Artery Blood Flow in Patients with Vertebro-Basilar Insufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Bozgeyik, Zulkif; Berilgen, Sait; Ozdemir, Huseyin; Ogur, Erkin [Firat University School of Medicine, Elazig(Turkmenistan); Tekatas, Aslan [Elazig Government Hospital, Elazig (Turkmenistan)

    2008-12-15

    To investigate the effects of sildenafil citrate (Viagra) on the vertebral artery blood flow of patients with vertebro-basilar insufficiency (VBI) using color duplex sonography (CDS). The study included 21 patients with VBI (aged 31-76; mean 61.0 +- 10.5 yrs). We administered a 50 mg oral dose of sildenafil citrate to all patients. Next, we measured the peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistive index (RI), pulsatility index (PI), diameter, area, and flow volume (FV) of vertebral arteries using CDS before the administration of sildenafil citrate; 45 minutes after, and 75 minutes after administration. Statistical testing was performed using SPSS for windows version 11.0. The statistical test used to determine the outcome of the analysis was the repeated measures analysis of variance (ANOVA) test. Compared to the baseline values, the vertebral artery diameter, area, and FV increased significantly following the administration of sildenafil citrate. The diameter, area and FV increased from 3.39 mm at 45 minutes to 3.64 mm at 75 minutes, 9.43 cm{sup 2} to 10.80 cm{sup 2} at 45 minutes and 10.81 cm{sup 2} at 75 minutes, as well as from 0.07 L/min at baseline to 0.09 L/min at 45 minutes and unchanged at 75 minutes, respectively. Sildenafil citrate elicited a significant effect on vertebral artery diameter, area and FVs

  4. Disintegration of comet nuclei

    Science.gov (United States)

    Ksanfomality, Leonid V.

    2012-02-01

    The breaking up of comets into separate pieces, each with its own tail, was seen many times by astronomers of the past. The phenomenon was in sharp contrast to the idea of the eternal and unchangeable celestial firmament and was commonly believed to be an omen of impending disaster, especially for comets with tails stretching across half the sky. It is only now that we have efficient enough space exploration tools to see comet nuclei and even - in the particular case of small comet Hartley-2 in 2010 - to watch their disintegration stage. There are also other suspected candidates for disintegration in the vast family of comet nuclei and other Solar System bodies.

  5. Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.

    Science.gov (United States)

    Lindberg, Ulrich; Witting, Nanna; Jørgensen, Stine Lundgaard; Vissing, John; Rostrup, Egill; Larsson, Henrik Bo Wiberg; Kruuse, Christina

    2017-01-01

    Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in muscles. This causes functional ischemia and contributes to muscle wasting. Similar functional ischemia may be present in brains of patients with BMD, who often have mild cognitive impairment, and nNOS may be important for the regulation of the microvascular circulation in the brain. We hypothesized that treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates nitric oxide responses, would augment both the blood oxygen level-dependent (BOLD) response and cerebral blood flow (CBF) in patients with BMD. Seventeen patients (mean ± SD age 38.5 ± 10.8 years) with BMD were included in this randomized, double-blind, placebo-controlled, crossover trial. Twelve patients completed the entire study. Effects of sildenafil were assessed by 3 T magnetic resonance (MR) scanning, evoked potentials, somatosensory task-induced BOLD functional MR imaging, regional and global perfusion, and angiography before and after 4 weeks of sildenafil, 20 mg (Revatio in gelatine capsules, oral, 3 times daily), or placebo treatment. Sildenafil increased the event-related sensory and visual BOLD response compared with placebo (p < 0.01). However, sildenafil did not alter CBF, measured by MR phase contrast mapping, or the arterial diameter of the middle cerebral artery, measured by MR angiography. We conclude that nNOS may play a role in event-related neurovascular responses. Further studies in patients with BMD may help clarify the roles of dystrophin and nNOS in neurovascular coupling in general, and in patients with BMD in particular.

  6. Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant

    Directory of Open Access Journals (Sweden)

    Luis Almenar Bonet

    2014-08-01

    Full Text Available The objective of the present work is to describe the experience with intravenous (IV sildenafil in heart transplant (HT patients with reactive pulmonary hypertension (PH who developed right ventricular dysfunction (RVD in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide. All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.

  7. Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant.

    Science.gov (United States)

    Bonet, Luis Almenar; Guillén, Rosario Vicente; Lázaro, Ignacio Sánchez; de la Fuente, Carmen; Osseyran, Faisa; Dolz, Luis Martínez; Hernández, Mónica Montero; Sanz, Manuel Portolés; Otero, Miguel Rivera; Sanz, Antonio Salvador

    2014-01-01

    The objective of the present work is to describe the experience with intravenous (IV) sildenafil in heart transplant (HT) patients with reactive pulmonary hypertension (PH) who developed right ventricular dysfunction (RVD) in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP) was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide). All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.

  8. Assessment of disintegration of rapidly disintegrating tablets by a visiometric liquid jet-mediated disintegration apparatus.

    Science.gov (United States)

    Desai, Parind M; Liew, Celine V; Heng, Paul W S

    2013-02-14

    The aim of this study was to develop a responsive disintegration test apparatus that is particularly suitable for rapidly disintegrating tablets (RDTs). The designed RDT disintegration apparatus consisted of disintegration compartment, stereomicroscope and high speed video camera. Computational fluid dynamics (CFD) was used to simulate 3 different designs of the compartment and to predict velocity and pressure patterns inside the compartment. The CFD preprocessor established the compartment models and the CFD solver determined the numerical solutions of the governing equations that described disintegration medium flow. Simulation was validated by good agreement between CFD and experimental results. Based on the results, the most suitable disintegration compartment was selected. Six types of commercial RDTs were used and disintegration times of these tablets were determined using the designed RDT disintegration apparatus and the USP disintegration apparatus. The results obtained using the designed apparatus correlated well to those obtained by the USP apparatus. Thus, the applied CFD approach had the potential to predict the fluid hydrodynamics for the design of optimal disintegration apparatus. The designed visiometric liquid jet-mediated disintegration apparatus for RDT provided efficient and precise determination of very short disintegration times of rapidly disintegrating dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2007-01-01

    Sildenafil citrate is a specific inhibitor of phosphodiesterase (PDE) type-5 and represents a powerful therapy for male erectile and fertility dysfunctions of different etiologies. Present study demonstrates whether sildenafil administration modifies seminal parameters in diabetic neuropathic patients. In this investigation 50 insulin dependent (IDDM) and 50 non insulin dependent (NIDDM) diabetic male patients with and without an objective evidence of neuropathy and 50 age matched non diabetic male controls were selected. Every male had age between 20 to 65 years with duration of diabetes distributed over 1 to 20 years. Treatment with 100 mg of oral sildenafil citrate on seminal parameters was evaluated by semen analysis in these patients. In both IDDM and NIDDM diabetic neuropathic patients, chronic sildenafil treatment exhibited a significant decrease in total sperm output and sperm concentration (p<0.001). On the other hand, sperm motility and semen volume were found to be increased by about 40% and 48% respectively in these patients, where as sperm morphology and quality of sperm motility remained unaffected. However both types of non neuropathic diabetics showed a non significant difference in all the above mentioned parameters when compared with the untreated groups and their respective control subjects. A comparison between IDDM and NIDDM neuropathic and non neuropathic diabetic groups further indicated a non significant difference in all the parameters of semen analysis. These findings suggest a chronic neuro physiological effect of sildenafil treatment on male fertility profile exclusively in diabetic neuropathic condition with an improvement in testicular function which was probably arrested due to some kind of testicular hyperplasia resulted by testicular necrosis and promoted spermatogenesis. Sildenafil seems to be associated with an improvement in the entire smooth musculature of reproductive tract and testicular morphology which was altered due to

  10. Unintegration, Disintegration and Deintegration

    Science.gov (United States)

    Urban, Elizabeth

    2006-01-01

    This paper is a response to a review of the conference titled, "Unintegration, Disintegration and Integration", written by Cathy Urwin and Maria Rhode in the ACP Bulletin. The review mentioned Michael Fordham, noting that he referred to a "good" kind of unintegration. In this paper, I point out that this is a somewhat misleading reference to what…

  11. Neutrino disintegration of deuterium

    International Nuclear Information System (INIS)

    Ying, S.; Haxton, W.; Henley, E.M.

    1989-01-01

    We calculate the rate of both neutral- and charged-current neutrino and antineutrino disintegration of deuterium. These rates are of interest for solar 8 B and hep ( 3 He + p) spectra and supernovae neutrinos, and are relevant for the Sudbury Neutrino Observatory (SNO)

  12. Development of fast disintegrating compressed tablets using amino acid as disintegration accelerator: evaluation of wetting and disintegration of tablet on the basis of surface free energy.

    Science.gov (United States)

    Fukami, Jinichi; Ozawa, Asuka; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide

    2005-12-01

    A fast disintegrating compressed tablet was formulated using amino acids, such as L-lysine HCl, L-alanine, glycine and L-tyrosine as disintegration accelerator. The tablets having the hardness of about 4 kgf were prepared and the effect of amino acids on the wetting time and disintegration time in the oral cavity of tablets was examined on the basis of surface free energy of amino acids. The wetting time of the tablets increased in the order of L-lysine HCl, L-alanine, glycine and L-tyrosine, whereas the disintegration time in the oral cavity of the tablets increased in the order of L-alanine, glycine, L-lysine HCl and L-tyrosine. These behaviors were well analyzed by the introduction of surface free energy. When the polar component of amino acid was large value or the dispersion component was small value, faster wetting of tablet was observed. When the dispersion component of amino acid was large value or the dispersion component was small value, faster disintegration of tablet was observed, expect of L-tyrosine tablet. The fast disintegration of tablets was explained by the theory presented by Matsumaru.

  13. Fast disintegrating tablets: Opportunity in drug delivery system

    Directory of Open Access Journals (Sweden)

    Ved Parkash

    2011-01-01

    Full Text Available Fast disintegrating tablets (FDTs have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed.

  14. Preparation, characterization and in vitro evaluation of a polyvinyl alcohol/sodium alginate based orodispersible film containing sildenafil citrate.

    Science.gov (United States)

    Shi, Li-Li; Xu, Wei-Juan; Cao, Qing-Ri; Yang, Mingshi; Cui, Jing-Hao

    2014-05-01

    In this work, we developed a sildenafil citrate (SC)-loaded polyvinyl alcohol (PVA)/sodium alginate (ALG-Na) based orodispersible film (ODF) using a solvent casting method. Formulation factors such as the type and amount of plasticizers and disintegrants were optimized on the basis of characteristics of blank ODF, including the disintegration time, elastic modulus (EM) and percentage of elongation (E%). SC-loaded ODF with a loading capacity up to 25 mg in an area of 6 cm2 was prepared and evaluated in terms of mechanical properties, disintegration time and dissolution rate. The surface morphology of ODF was visualized under a scanning electron microscope (SEM). The physicochemical properties of ODF were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The blank ODF composed of PVA, polyethylene glycol 400 (PEG 400) and ALG-Na (20:5:2, w/w) had a remarkably short disintegration time of about 20 s. However, the loading of drug extended the disintegration time (100 s) of ODF, while it still maintained satisfactory mechanical properties. SC was homogenously dispersed throughout the films and the crystalline form of drug changed, with strong hydrogen bonding between the drug and carriers. The PVA/ALG-Na based ODF containing SC prepared by the simple solvent casting method might be an alternative to conventional SC tablets for the treatment of male erectile dysfunction.

  15. Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual responses in Saudi men with erectile dysfunction in routine clinical practice.

    Science.gov (United States)

    Ali, Syed Tabrez

    2008-07-01

    Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction, yet enhanced satisfaction has been infrequently assessed in the sexual trials. We evaluated the efficacy of sildenafil vs. tadalafil, in Saudi men with erectile dysfunction and determined the self-based rating of medicinal preference. Sildenafil citrate (Viagra) is a potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Whereas cGMP is a second messenger for the vasodilator effects of nitric oxide causing smooth muscle relaxation, which in turn leads to penile erection; however the mechanism by which cGMP stimulates relaxation of the smooth muscles remains to be elucidated. Both sildenafil and tadalafil have a rapid onset with the effectiveness up to 4 hours and 36 hours respectively. In this study subjects treated with 100 mg oral dose of sildenafil / 20 mg tadalafil were found to be associated with higher mean scores for the questions of the International Index of Erectile Function (IIEF). Frequency of penetration and maintenance of erection after sexual penetration and/or during masturbation were found to be enhanced significantly (p<0.001) in both sildenafil/tadalafil treated men. Similarly mean domain of erectile function, orgasmic function, and intercourse satisfaction also showed a significantly positive improvement (p/0.001) in both the treated groups in comparison with their age matched untreated controls. Interestingly in all the cases, tadalafil group showed considerably greater positive responses than the sildenafil group but within the same significant levels. Strikingly the sexual-desire domain in sildenafil treated men with respect to their aged matched controls

  16. Sildenafil Stimulates Aqueous Humor Turnover in Rabbits

    Science.gov (United States)

    Alvarez, Lawrence J.; Zamudio, Aldo C.; Candia, Oscar A.

    2013-01-01

    Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈ 2 hrs of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈ 45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90–120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 μL/min to 3.14 μL/min (PViagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation. PMID:23562660

  17. Disintegration of comet nuclei

    International Nuclear Information System (INIS)

    Ksanfomality, Leonid V

    2012-01-01

    The breaking up of comets into separate pieces, each with its own tail, was seen many times by astronomers of the past. The phenomenon was in sharp contrast to the idea of the eternal and unchangeable celestial firmament and was commonly believed to be an omen of impending disaster, especially for comets with tails stretching across half the sky. It is only now that we have efficient enough space exploration tools to see comet nuclei and even - in the particular case of small comet Hartley-2 in 2010 - to watch their disintegration stage. There are also other suspected candidates for disintegration in the vast family of comet nuclei and other Solar System bodies. (physics of our days)

  18. ALERT: Revatio is another brand name for sildenafil.

    Science.gov (United States)

    Koczmara, Christine; Hyland, Sylvia; Greenall, Julie

    2009-01-01

    In this column, the authors highlight a medication incident that occurred with Revatio (sildenafil), along with the learnings and recommendations from a previously published ISMP Canada Safety Bulletin. It is well-known to health care practitioners that use of nitroglycerin therapy is contraindicated in patients taking sildenafil (commonly known as Viagra). Many health care practitioners may be unaware that sildenafil is also marketed under the brand name Revatio for treatment of primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disease. The following incident signals the need to heighten the awareness that Revatio is a brand name for sildenafil.

  19. Bilateral cerebral hemispheric infarction associated with sildenafil citrate (Viagra) use.

    Science.gov (United States)

    Kim, K-K; Kim, D G; Ku, Y H; Lee, Y J; Kim, W-C; Kim, O J; Kim, H S

    2008-03-01

    Sildenafil citrate (Viagra) is one of the frequently prescribed drugs for men with erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil and about 1 h later, he complained of chest discomfort, palpitation and dizziness followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic resonance imaging documented acute bilateral hemispheric infarction, and cerebral angiography showed occluded bilateral MCA. Despite significant bilateral MCA stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume that cerebral infarction was caused by cardioembolism with sildenafil use.

  20. Childhood disintegrative disorder

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik

    2003-01-01

    In 1908 a Viennese remedial educator Theodor Heller described six children under the name of dementia infantilis who had insidiously developed a severe mental regression between the 3rd and 4th years of life after normal mental development. Neuropathological and other medical conditions...... are sometimes associated with this disorder, but contrary to earlier belief this is not typical. Interest in childhood disintegrative disorder has increased markedly in recent years and in this review attention is given to more recently published cases based on ICD-9, ICD-10 and DSM-IV diagnostic systems...

  1. Satellite disintegration dynamics

    Science.gov (United States)

    Dasenbrock, R. R.; Kaufman, B.; Heard, W. B.

    1975-01-01

    The subject of satellite disintegration is examined in detail. Elements of the orbits of individual fragments, determined by DOD space surveillance systems, are used to accurately predict the time and place of fragmentation. Dual time independent and time dependent analyses are performed for simulated and real breakups. Methods of statistical mechanics are used to study the evolution of the fragment clouds. The fragments are treated as an ensemble of non-interacting particles. A solution of Liouville's equation is obtained which enables the spatial density to be calculated as a function of position, time and initial velocity distribution.

  2. Cerebral venous thrombosis associated with sildenafil intake

    International Nuclear Information System (INIS)

    Miranda Hernández, José Luis; Fernández Cué, Leda; Garzón Cutiño, Lisbel; Gómez Viera, Nelson; Pérez Esquivel, Lianet

    2016-01-01

    A 59 year-old male patient with a history of hypertension and regular consumption of sildenafil entered the service because of acute stroke and headache seizure. Physical examination detected left hemiplegia. By skull nuclear gadolinium magnetic resonance, an expansive lesion is observed which caught heterogeneously contrast. Possible diagnosis of high-grade brain glioma was raised. Right frontoparietal craniotomy was performed and a tumor lesion was not visualized. After ruling out the presence of high-grade glioma, the diagnosis of hemorrhagic venous infarction was assessed. CT angiography and clotting was made to rule out prothrombotic states to justify this disease entity. Special hematology studies were within normal values. The case was concluded as a venous sinus thrombosis associated with the use of sildenafil. (author)

  3. Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress.

    Science.gov (United States)

    Sikandaner, Hu Erxidan; Park, So Young; Kim, Min Jung; Park, Shi Nae; Yang, Dong Won

    2017-02-15

    Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level. Sildenafil (15mg/kg) was orally administered 30min before noise exposure for 14days. Behavioral assessments were performed using novel object recognition (NOR) test and radial arm maze (RAM) test. Higher levels of memory dysfunction and oxidative stress were observed in noise alone-induced mice compared to control group. Interestingly, sildenafil administration increased memory performance, decreased oxidative stress, and increased neuroprotection in the hippocampus region of noise alone-induced mice likely through affecting memory related pathways such as cGMP/PKG/CREB and p25/CDK5, and induction of free radical scavengers such as SOD1, SOD2, SOD3, Prdx5, and catalase in the brain of stressed mice. Copyright © 2016. Published by Elsevier B.V.

  4. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  5. Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy

    2010-10-01

    The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30-35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.

  6. Disintegration of a Liquid Jet

    Science.gov (United States)

    Haenlein, A

    1932-01-01

    This report presents an experimental determination of the process of disintegration and atomization in its simplest form, and the influence of the physical properties of the liquid to be atomized on the disintegration of the jet. Particular attention was paid to the investigation of the process of atomization.

  7. Central Retinal Vein Occlusion AssociatedWith Sildenafil (Viagra ...

    African Journals Online (AJOL)

    Objectives To report the occurrence of a severe, blinding and irreversible adverse effect following use of the drug sildenafil citrate (Viagra). Methods This is a case report of a 60 year old man who presented with unilateral, suddenonset, painless, visual loss following the use of sildenafil citrate 100mg twice weekly, ...

  8. Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

    Directory of Open Access Journals (Sweden)

    Stephanie Leigh Siehr

    2015-03-01

    Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

  9. Sildenafil in the management of neonates with PPHN: A rural ...

    African Journals Online (AJOL)

    0.43 - 6.8/1 000 live births and carries a high risk of mortality .... pressure and number of ventilation days lower in the sildenafil group. ... premature baby treated with sildenafil ... Sudden decreases in or loss of hearing following ... birth weight.

  10. A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

    Science.gov (United States)

    Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

    2016-08-01

    A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Cerebral haemodynamic response or excitability is not affected by sildenafil

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Hansen, Adam E; Larsson, Henrik B W

    2009-01-01

    Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70......) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP...... amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication...

  12. Disintegration of liquid sheets

    Science.gov (United States)

    Mansour, Adel; Chigier, Norman

    1990-01-01

    The development, stability, and disintegration of liquid sheets issuing from a two-dimensional air-assisted nozzle is studied. Detailed measurements of mean drop size and velocity are made using a phase Doppler particle analyzer. Without air flow the liquid sheet converges toward the axis as a result of surface tension forces. With airflow a quasi-two-dimensional expanding spray is formed. The air flow causes small variations in sheet thickness to develop into major disturbances with the result that disruption starts before the formation of the main break-up region. In the two-dimensional variable geometry air-blast atomizer, it is shown that the air flow is responsible for the formation of large, ordered, and small chaotic 'cell' structures.

  13. Turbine disintegration debris

    International Nuclear Information System (INIS)

    Holecek, M.; Martinec, P.; Malotin, V.; Peleska, P.; Voldrich, J.

    1997-01-01

    The determination, evaluation and analysis of possible unacceptable consequences of the disintegration turbine (turbo-set) missiles is a part of the wide conceived project put by the company Nuclear Power Plant Mochovce (NPPM), the Slovak Republic. The aim of the project is to take measures reducing the probability of striking a target of safety importance in NPPM by a turbine (turbo-set) missile below the prescribed limit of 10 -6 per turbine year. Following the IAEA Safety Guides, all potential events leading to the generation of a missile are to be analysed. It is necessary to evaluate the probability of unacceptable consequences of such missiles and analyse each event whose probability is not acceptable low. This complex problem thus carries especially: complex analysis of fragment generation; evaluation of the probability of unacceptable events; location of strike zones of possible turbine missiles; assessment the possibility of the turbo-set casing penetration; and projection of additional design requirements if necessary

  14. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Thomsen, Lars Lykke; Birk, Steffen

    2003-01-01

    -controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (r...... that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use...

  15. Optimisation of Ondansetron Orally Disintegrating Tablets Using ...

    African Journals Online (AJOL)

    HP

    Methods: Different amounts of two different commercial superdisintegrants commonly used in ODT ... analysed using gene expression programming (GEP) and neuro-fuzzy logic (NFL) models. ..... analyse historical data derived from different.

  16. Development and optimization of fluoxetine orally disintegrating ...

    African Journals Online (AJOL)

    Bahaa E Ali, Abdullah K Rabba, Mohamed H Fayed, Khalid M El-Say, Mohammad Khalid Anwer, Mohammad Javed Ansari, Ramadan Al-Shdefat, Gamal A Gabr ... The design suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and compression force (X3) and then their effect was ...

  17. Clinical deterioration after sildenafil cessation in patients with pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Anne M Keogh

    2008-10-01

    Full Text Available Anne M Keogh, Andrew Jabbour, Christopher S Hayward, Peter S MacdonaldHeart Lung Transplant Unit, St Vincent’s Hospital, Sydney, New South Wales, AustraliaAbstract: Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE-5. Its chronic administration has been shown to improve exercise capacity, World Health Organization functional class, and haemodynamics in patients with symptomatic pulmonary arterial hypertension (PAH. There is however, no data describing the clinical consequences of sudden cessation of sildenafil treatment. In this series, 9 patients with NYHA Class II–IV PAH who were stable on 2 months of sildenafil monotherapy, had their sildenafil ceased to accommodate a 2-week washout period, required for enrollment in research involving an endothelin receptor antagonist. Six minute walk distance (SMWD and clinical assessments were performed before cessation of sildenafil, and again 2 weeks later. Over the course of this 2-week washout period, 6 of the 9 patients reported increased breathlessness and fatigue, 1 of these was hospitalized with worsening right heart failure. The SMWD fell in 6 patients, with falls of greater than 100 m recorded in 4 patients. This was accompanied by a worsening of NYHA Class from 2.5 ± 0.2 to 3.1 ± 0.1 (mean ± SEM, p = 0.01. These data indicate that sudden cessation of sildenafil monotherapy, in patients with PAH, carries with it a significant and unpredictable risk of rapid clinical deterioration. We recommend that if sildenafil needs to be ceased, it would be more prudent to consider concurrent vasodilator therapy before the gradual cessation of sildenafil.Keywords: sildenafil, pulmonary hypertension, phosphodiesterase inhibitor

  18. Electrode for disintegrating metallic material

    International Nuclear Information System (INIS)

    Persang, J.C.

    1985-01-01

    A graphite electrode is provided for disintegrating and removing metallic material from a workpiece, e.g., such as portions of a nuclear reactor to be repaired while in an underwater and/or radioactive environment. The electrode is provided with a plurality of openings extending outwardly, and a manifold for supplying a mixture of water and compressed gas to be discharged through the openings for sweeping away the disintegrated metallic material during use of the electrode

  19. Cerebral haemodynamic response or excitability is not affected by sildenafil

    DEFF Research Database (Denmark)

    Kruuse, Christina; Hansen, Adam E; Larsson, Henrik B W

    2009-01-01

    Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70...... amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication...

  20. Central Retinal Vein Occlusion AssociatedWith Sildenafil (Viagra

    Directory of Open Access Journals (Sweden)

    H C Obiudu

    2010-01-01

    Conclusion - Central retinal vein occlusion is a possible adverse effect of sildenafil use. Physicians should be vigilant while prescribing thismedication and avoid its use in patients with elevated intraocular pressure

  1. Sildenafil (Viagra). Verträglichkeit, Kontraindikationen, Arzneimittelinteraktionen

    NARCIS (Netherlands)

    Sperling, H.; Michel, M. C.; Rübben, H.

    1999-01-01

    Placebo-controlled studies have clearly demonstrated the efficacy of sildenafil in the treatment of erectile dysfunction. It's tolerability cannot yet be judged definitively based on the available information. Some findings indicate that in addition to established contraindications (allergy against

  2. Haematological changes and wound healing effects of sildenafil ...

    African Journals Online (AJOL)

    Group G were normal rats without wound treated with sildenafil citrate as in Group A. Blood samples were taken before (day 0) and after the administration of the sildenafil citrate on day 7, 14 and 21. The results of the study showed significant decreased in red blood cells count from 6.28 ± 0.46 × 106 to 2.81 ± 0.46 × 106 in ...

  3. Sorption and Transport of Sildenafil in Natural Soils

    Science.gov (United States)

    Boudinot, F. G.; Vulava, V. M.

    2013-12-01

    Pharmaceutical Chemicals (PCs) mainly enter our ecosystems from discharges of treated wastewater and have direct effects on the ecological health of that area. Sildenafil citrate (Viagra) is one such PC, whose presence has been reported in stream waters. Although one study has shown that sildenafil is not harmful in bacterial and fungal environments, there remains much unknown about its fate elsewhere in ecosystems. Sildenafil is a complex organic molecule with two amino functional groups that result in pKa's of 7.27 and 5.97. It also has a high solubility of 3.5 g/L. Given that sildenafil consumption (and concurrently disposal) is on the rise, it is essential that its behavior in the natural environment be better understood. The goal of this study was to quantify the sorption and transport behavior of sildenafil in differing natural soils with varying compositions. Pristine A- and B- horizon soil samples from several soil series were collected in a managed forest near Charleston, SC and used for these studies. The soils were characterized for physical and chemical properties: soil organic matter content ranged between 0.6-7.6%, clay content between 6-20%, and soil pH between 4-5. These soils were then used to perform kinetic reaction, sorption, and column transport experiments. Batch kinetic experiments showed a fast reaction rate in both clay-rich and organic-rich soils and an equilibration time of less than 24 hours. Batch reactor sorption experiments provided data for sorption isotherms (plot of sildenafil in solution, C vs. sildenafil sorbed in soil, q) which were nonlinear. The isotherms were fit using Freundlich model (q=KfCn, where Kf and n are fitting parameters). Sildenafil sorbed more strongly to clay-rich soils compared with organic-rich soils with less clay. It is hypothesized that permanent negative charge on clay mineral surfaces form ionic bonds with positively charged amines in sildenafil in acidic pHs. Transport experiments were conducted using

  4. A critical review on tablet disintegration.

    Science.gov (United States)

    Quodbach, Julian; Kleinebudde, Peter

    2016-09-01

    Tablet disintegration is an important factor for drug release and can be modified with excipients called tablet disintegrants. Tablet disintegrants act via different mechanisms and the efficacy of these excipients is influenced by various factors. In this review, the existing literature on tablet disintegration is critically reviewed. Potential disintegration mechanisms, as well as impact factors on the disintegration process will be discussed based on experimental evidence. Search terms for Scopus and Web of Science included "tablet disintegration", "mechanism tablet disintegration", "superdisintegrants", "disintegrants", "swelling force", "disintegration force", "disintegration mechanisms", as well as brand names of commonly applied superdisintegrants. References of identified papers were screened as well. Experimental data supports swelling and shape recovery as main mechanisms of action of disintegrants. Other tablet excipients and different manufacturing techniques greatly influence the disintegration process. The use of different excipients, experimental setups and manufacturing techniques, as well as the demand for original research led to a distinct patchwork of knowledge. Broader, more systematic approaches are necessary not only to structure the past but also future findings.

  5. [Stability of disintegration in health food].

    Science.gov (United States)

    Ma, Lan; Zhao, Xin; Zhou, Shuang; Yang, Dajin

    2012-11-01

    To study the change of disintegration of different formulation samples which stored in the artificial climate box or room temperature and provide the technical support for health food monitoring. According to the method of Chinese Pharmacopoeia and British Pharmacopoeia. Appendix XII A. Disintegration 2010. Disintegration of the non-accelerate, accelerated after 1, 2 and 3 months samples were determined by the disintegrator, respectively. Sample properties, the ingredients of the samples, the proportions of the capsule and treatment methods have some effect on the stability of the disintegration. The disintegration time of health food will be changed particularly after they were accelerated under the condition of (38 +/- 1) degrees C/75% RH. Especially the disintegration time of soft capsules were significantly prolonged. The composition and properties of samples were the main factors that affected the disintegration.

  6. Capsule shell material impacts the in vitro disintegration and dissolution behaviour of a green tea extract

    OpenAIRE

    Glube, Natalie; Moos, Lea von; Duchateau, Guus

    2013-01-01

    Purpose In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release. Methods A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times we...

  7. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    DEFF Research Database (Denmark)

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea

    2009-01-01

    BACKGROUND: Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth...

  8. The Disintegration of Teacher Preparation

    Science.gov (United States)

    Baines, Lawrence A.

    2010-01-01

    The disintegration of teacher certification programs in the united States holds an eerie similarity to the recent meltdown of American financial institutions. Similarly, the No Child Left Behind Act of 2001, whose purported purpose was to ensure that all students get highly qualified teachers (HQT), has had an unintentionally devastating effect on…

  9. Comparative Evaluation of the Aphrodisiac efficacy of Sildenafil and Carpolobia lutea Root Extract in Male Rabbits

    Directory of Open Access Journals (Sweden)

    Ayobami Dare

    2015-12-01

    Full Text Available Aims: In spite of folkloric use of the root of Carpolobia lutea as sexual stimulant in man, there has been limited scientific proof of its efficacy. This study evaluates efficacy of methanol extract of Carpolobia lutea root (MECLR on sexual activity of male rabbits. Methods: Twenty adult male rabbits were grouped into four of five rabbits each. Groups 1-4 were treated orally for 28 days with 2ml/kg 1% tween 20 (vehicle, 40mg/kg MECLR, 80mg/kg MECLR, and 0.5mg/kg sildenafil citrate respectively. Sexual activities of males from each group was assessed by cohabiting them with sexually receptive female at estrus on days 0,1,3 and 5 using digital camera mounted on mating arena. Serum testosterone and nitric oxide concentration of the corpora cavernosa homogenates were also determined. Results: MECLR caused a dose dependent significant increase in mount frequency, intromission frequency and ejaculatory latency, while it reduced mount latency, intromission latency and post ejaculatory latency (similar to sildenafil citrate when compared with the control. MECLR also caused a significant increase in nitric oxide concentration in corpora cavernosa but no change in serum testosterone concentration. Conclusions: Results suggest that MECLR enhances male sexual activity possibly by augmenting nitric oxide concentration. This study thus provides novel scientific rationale for the use of Carpolobia lutea in the management of penile erectile dysfunction and impaired libido. [J Intercult Ethnopharmacol 2015; 4(4.000: 302-307

  10. Effect of a Disintegration Mechanism on Wetting, Water Absorption, and Disintegration Time of Orodispersible Tablets

    OpenAIRE

    Pabari, RM; Ramtoola, Z

    2012-01-01

    The aim of this study was to evaluate the influence of disintegration mechanism of various types of disintegrants on the absorption ratio (AR), wetting time (WT), and disintegration time (DT) of orodispersible tablets (ODTs). ODTs were prepared by direct compression using mannitol as filler and disintegrants selected from a range of swellable, osmotic, and porous disintegrants. Tablets formed were characterized for their water AR, WT, and DT. The porosity and mechanical strength of the tablet...

  11. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

    Science.gov (United States)

    Wareing, Mark; Myers, Jenny E; O'Hara, Maureen; Baker, Philip N

    2005-05-01

    Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

  12. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  13. Application of general multilevel factorial design with formulation of fast disintegrating tablets containing croscaremellose sodium and Disintequick MCC-25.

    Science.gov (United States)

    Solaiman, Amanda; Suliman, Ammar Said; Shinde, Swapnil; Naz, Sidra; Elkordy, Amal Ali

    2016-03-30

    Despite the popularity of orally fast disintegrating tablets (FDTs), their formulation can sometimes be challenging, producing tablets with either poor mechanical properties or high disintegration times. The aim of this research was to enhance the properties of FDTs produced by direct compression to have both sufficient hardness to withstand manual handling, and rapid disintegration time. General multilevel factorial design was applied to optimise and evaluate main and interaction effects of independent variables (i) disintegrant concentration, (ii) % filler (Disintequick MCC-25) to mannitol on the responses hardness, tensile strength and disintegration time. In this experiment mannitol was used as a diluent, Disintequick MCC-25 (to best of our knowledge there is no publication available yet for its use with FDTs) was termed in this study as a filler and croscaremellose sodium was used as the superdisintegrant. Seven formulations were prepared following a progressive two-stage approach. Each stage involved the change in the ratio of excipients (Mannitol:Filler) (1:0), (1:0.25), (1:0.50), (1:1), (0.50:1), (0.25:1), (0:1) w/w and concentration of superdisintegrant (1%, 3%, 5%, 7%, 10% w/w). All FDTs were tested for different parameters such as diameter, hardness, tensile strength, thickness, friability and disintegration time. The results of multiple linear regression analysis show a good degree of correlation between experimental (R(2):0.84, 0.94, 0.91) and predicted response (R(2):0.83, 0.96, 0.95) for hardness, tensile strength and disintegration time respectively. The optimum formulations (regarding disintegration time with acceptable hardness and friability properties) consisted of: (i) 5% w/w disintegrant and 20% w/w filler to mannitol, showing a disintegration time of 30s, a hardness of 66.6N (6.8 kg/cm(2)) and friability of 2.2%; (ii) 7% or 10% w/w disintegrant with 33.33% w/w filler to mannitol, showing disintegration time of 84 s (for 7% disintegrant) and

  14. Sub- and supercritical jet disintegration

    Science.gov (United States)

    DeSouza, Shaun; Segal, Corin

    2017-04-01

    Shadowgraph visualization and Planar Laser Induced Fluorescence (PLIF) are applied to single orifice injection in the same facility and same fluid conditions to analyze sub- to supercritical jet disintegration and mixing. The comparison includes jet disintegration and lateral spreading angle. The results indicate that the shadowgraph data are in agreement with previous visualization studies but differ from the PLIF results that provided quantitative measurement of central jet plane density and density gradients. The study further evaluated the effect of thermodynamic conditions on droplet production and quantified droplet size and distribution. The results indicate an increase in the normalized drop diameter and a decrease in the droplet population with increasing chamber temperatures. Droplet size and distribution were found to be independent of chamber pressure.

  15. Continuous Disintegrations of Gaussian Processes

    OpenAIRE

    LaGatta, Tom

    2010-01-01

    The goal of this paper is to understand the conditional law of a stochastic process once it has been observed over an interval. To make this precise, we introduce the notion of a continuous disintegration: a regular conditional probability measure which varies continuously in the conditioned parameter. The conditioning is infinite-dimensional in character, which leads us to consider the general case of probability measures in Banach spaces. Our main result is that for a certain quantity $M$ b...

  16. Ocular safety of Viagra, (sildenafil citrate).

    Science.gov (United States)

    Laties, A M; Fraunfelder, F T

    1999-01-01

    To date, sildenafil citrate (Viagra) gives every evidence of being a safe drug for the eye despite a series of expressed concerns. A review of how its ocular safety profile has been identified offers insights into the strengths and weaknesses of present systems and resources for judging the ocular safety of Viagra or, for that matter, of any new drug. Such insights include: The great value of careful, informed assessment of preclinical information gleaned from laboratory experiments. By and large, such assessments point the way toward appropriate clinical evaluation. For Viagra, early in its development it was noted that besides exerting a major inhibitory effect on the intended target, the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the closely related PDE6, located in the retina. For this reason, preclinical evaluation of the drug included electroretinography plus postmortem histology. In addition, an extended eye examination was incorporated into clinical protocols. The often chaotic but invaluable information stream that becomes available once marketing approval has been gained and large populations begin to use a drug. False alarms, misattribution, and erroneous information are the order of the day. Nevertheless, as information accumulates, patterns of response clarify and the true nature of special susceptibility for subpopulations, if any, becomes apparent. A role for the astute clinician remains: Subtle changes or unusual risks for subpopulations can be missed entirely for long periods of time. A manifest need for improvement in evaluation of postmarketing side-effects. This need has led to the establishment of a new discipline: pharmacoepidemiology. In ophthalmology, the National Registry of Drug Induced Ocular Side-Effects maintains a constant and invaluable surveillance. Examples are supplied to illustrate each of these major points: Our presentation will include data gleaned from

  17. Effect of sildenafil on erectile dysfunction in spinal Cord injured ...

    African Journals Online (AJOL)

    Effect of sildenafil on erectile dysfunction in spinal Cord injured patients. ... Trauma was the etiology in 87.5% of the cases (44% were road accidents). 12/16 patients were paraplegics (10 above ... in SCI patients. This approach is compatible with the efforts to improve the quality of life and rehabilitation of these patients.

  18. Sildenafil in the management of neonates with PPHN: A rural ...

    African Journals Online (AJOL)

    cytochrome P450 enzyme system, has an elimination half-life ... Sildenafil appears to be beneficial in the treatment of PPHN and its use can be considered in the management of selected cases .... 5 mg/ml, and dilute with 4 parts water before administration .... Kumar S. Indian doctor in protest after using Viagra to save 'blue.

  19. Brexit and the problem of European disintegration

    DEFF Research Database (Denmark)

    Rosamond, Ben

    2016-01-01

    The Brexit referendum provokes speculation about the likelihood of European disintegration. This article discusses how scholarship might deal with the issue of disintegration and argues that it should be thought of as an indeterminate process rather than an identifiable outcome. Within the EU...... system, Brexit is likely to unleash disintegrative dynamics, which could see the EU stagnate into a suboptimal institutional equilibrium. At the same time, EU studies needs to lift its gaze beyond the internal dynamics of the EU system to consider the disintegration of the democratic capitalist compact...

  20. In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

    Science.gov (United States)

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2008-04-01

    The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

  1. Molecular characterization of microbial population dynamics during sildenafil citrate degradation.

    Science.gov (United States)

    De Felice, Bruna; Argenziano, Carolina; Guida, Marco; Trifuoggi, Marco; Russo, Francesca; Condorelli, Valerio; Inglese, Mafalda

    2009-02-01

    Little is known about pharmaceutical and personal care products pollutants (PPCPs), but there is a growing interest in how they might impact the environment and microbial communities. The widespread use of Viagra (sildenafil citrate) has attracted great attention because of the high usage rate, the unpredictable disposal and the unknown potential effects on wildlife and the environment. Until now information regarding the impact of Viagra on microbial community in water environment has not been reported. In this research, for the first time, the genetic profile of the microbial community, developing in a Viagra polluted water environment, was evaluated by means of the 16S and 18S rRNA genes, for bacteria and fungi, respectively, amplified by polymerase chain reaction (PCR) and separated using the denaturing gradient gel electrophoresis (DGGE) technique. The DGGE results revealed a complex microbial community structure with most of the population persisting throughout the experimental period. DNA sequences from bands observed in the different denaturing gradient gel electrophoresis profiles exhibited the highest degree of identity to uncultured bacteria and fungi found previously mainly in polluted environmental and treating bioreactors. Biotransformation ability of sildenafil citrate by the microbial pool was studied and the capability of these microorganisms to detoxify a polluted water ecosystem was assessed. The bacterial and fungal population was able to degrade sildenafil citrate entirely. Additionally, assays conducted on Daphnia magna, algal growth inhibition assay and cell viability determination on HepG2 human cells showed that biotransformation products obtained from the bacterial growth was not toxic. The higher removal efficiency for sildenafil citrate and the lack of toxicity by the biotransformation products obtained showed that the microbial community identified here represented a composite population that might have biotechnological relevance to

  2. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

    Science.gov (United States)

    Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

    2013-04-01

    Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

  3. Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

    Science.gov (United States)

    Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

    2008-02-01

    The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

  4. Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets.

    Science.gov (United States)

    Pabari, Rm; Ramtoola, Z

    2012-07-01

    The aim of this study was to evaluate the influence of disintegration mechanism of various types of disintegrants on the absorption ratio (AR), wetting time (WT), and disintegration time (DT) of orodispersible tablets (ODTs). ODTs were prepared by direct compression using mannitol as filler and disintegrants selected from a range of swellable, osmotic, and porous disintegrants. Tablets formed were characterized for their water AR, WT, and DT. The porosity and mechanical strength of the tablets were also measured. Results show that the DT of formulated ODTs was directly related to the WT and was a function of the disintegration mechanism of the disintegrant used. The lowest WT and DT were observed for tablets formulated using the osmotic disintegrant sodium citrate and these tablets also showed the lowest AR and porosity. The wetting and disintegration of tablets containing the highly swellable disintegrant, sodium starch glycollate, was slowest despite their high water AR and high tablet porosity. Rapid wetting and disintegration of ODTs were therefore not necessarily related to the porosity of the tablets.

  5. Improving performance through vertical disintegration: Evidence from UK manufacturing firms

    OpenAIRE

    Desyllas, Panos

    2009-01-01

    Unlike previous work on the vertical integration-performance relationship, we investigate the performance consequences of vertical disintegration. We offer a theoretical justification for the disintegration decision and we condition the disintegration effect on performance on the initial degree of firm integration, the timing and the direction of disintegration. Using a sample of UK manufacturing firms and controlling for disintegration endogeneity, we find that disintegration eventually resu...

  6. Lattice-Boltzmann Simulation of Tablet Disintegration

    Science.gov (United States)

    Jiang, Jiaolong; Sun, Ning; Gersappe, Dilip

    Using the lattice-Boltzmann method, we developed a 2D model to study the tablet disintegration involving the swelling and wicking mechanisms. The surface area and disintegration profile of each component were obtained by tracking the tablet structure in the simulation. Compared to pure wicking, the total surface area is larger for swelling and wicking, which indicates that the swelling force breaks the neighboring bonds. The disintegration profiles show that the tablet disintegrates faster than pure wicking, and there are more wetted active pharmaceutical ingredient particles distributed on smaller clusters. Our results indicate how the porosity would affect the disintegration process by changing the wetting area of the tablet as well as by changing the swelling force propagation.

  7. The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus- A histological study

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-07-01

    Full Text Available The histological effect of oral administration of sildenafil citrate (Viagra, commonly used as an aphrodisiac and for the treatment of erectile dysfunction on one of the visual relay centres namely the lateral geniculate body (LGB of adult Wistar rat was carefully studied. The rats of both sexes (n=24, average weight of 202g were randomly assigned into three treatment (n=18 and control (n=6 groups. The rats in the treatment groups ‘A’, ‘B’ and ‘C’ received respectively, 0.25mg/kg, 0.70mg/kg and 1.43mg/kg body weight of sildenafil citrate base dissolved in distilled water daily for 30 days, through orogastric feeding tube, while that of the control group D, received equal volume of distilled water daily during the period of the experiment. The rats were fed with growers’ mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria and were given water liberally. The rats were sacrificed on day thirty-one of the experiment. The lateral geniculate body (LGB was carefully dissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after H&E method indicated that the treated section of the lateral geniculate body (LGB showed some varying degree of reduced cellular population based on its sparse distribution, degenerative changes, cellular hypertrophy, and intercellular vacuolations appearing in the stroma. Varying dosage and long administration of sildenafil citrate may have some deleterious effects on the neurons of the intracranial visual relay centre and this may probably have some adverse effects on visual sensibilities by its deleterious effects on the cells of the lateral geniculate body (LGB of adult Wistar rats. It is therefore recommended that further studies aimed at corroborating these observations be carried out.

  8. Disintegration phenomena in Comet West

    Science.gov (United States)

    Sekanina, Z.

    1976-01-01

    Two peculiarities of Comet West, the multiple splitting of the nucleus as seen in telescope observations and the complex structure of the dust tail, are discussed. A method of analysis based on the premise that the observed rate of separation of a fragment from the principal nucleus is determined by the difference in effective solar attraction acting on the bodies is applied to investigate the motion of the four fragments that separated from the nucleus of Comet West. The predicted motion of the fragments is in good agreement with available observations. It is suggested that the 'synchronic' bands of the dust tail consist of tiny fragments from relatively large particles that burst after release from the comet. The unusual orientation of these bands and their high surface brightness relative to the diffuse tail are explained by a sudden increase in the particle acceleration and in the total scattering surface as the result of the disintegration of the larger particles.

  9. Tarsal bone disintegration in leprosy

    International Nuclear Information System (INIS)

    Haverson, G.; Warren, A.G.

    1979-01-01

    Tarsal bone disintegration is characterised by fragmentation and progressive collapse of one or more tarsal bones. It occurs in 10% of leprosy patients, and is responsible for many severe foot deformities associated with this disease. The main cause is micro-traumata, but sensory impairment, sepsis and osteoporosis are predisposing factors. In this series of 400 consecutive patients the talus and navicular were involved most frequently (72% of 119 tarsal lesions). Treatment, including prolonged immobilisation of the foot, results in dense sclerosis of the affected bone, and leaves a functional limb. Initial radiological features include bone fragmentation, calcified fragments in adjacent soft tissues, linear fractures, progressive compression and deformity of the affected bone, loss of density of the affected bone and flattening of the longitudinal plantar arch. Illustrative case histories are presented, and the differential diagnosis discussed. (author)

  10. Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

    Science.gov (United States)

    Balata, Gehan F; Zidan, Ahmad S; Abourehab, Mohamad AS; Essa, Ebtessam A

    2016-01-01

    The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin. PMID:27757012

  11. Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene-polypropylene block copolymer for maximized disintegration and dissolution.

    Science.gov (United States)

    Balata, Gehan F; Zidan, Ahmad S; Abourehab, Mohamad As; Essa, Ebtessam A

    2016-01-01

    The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene-polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 3 2 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT's porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin.

  12. Chitin's Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments.

    Science.gov (United States)

    Chaheen, Mohammad; Soulairol, Ian; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

    2017-07-01

    Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure "Py" shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. Visual field defect as a presenting sign for hemorrhagic stroke caused by sildenafil

    Directory of Open Access Journals (Sweden)

    Mehdizadeh Morteza

    2008-01-01

    Full Text Available Herein, we describe the presenting symptoms, history, ophthalmic examination, visual fields and brain magnetic resonance imaging of a patient who developed left homonymous hemianopia due to right occipital lobe hemorrhage after ingestion of sildenafil citrate (Novagra Forte. To the best of our knowledge, association of homonymous hemianopia with sildenafil usage has not been reported before.

  14. Sildenafil no tratamento da hipertensão arterial pulmonar idiopática em crianças e adolescentes Sildenafil in the management of idiopathic pulmonary arterial hypertension in children and adolescents

    Directory of Open Access Journals (Sweden)

    Edmundo Clarindo Oliveira

    2005-10-01

    Full Text Available OBJETIVO: Este artigo tem por objetivo relatar a experiência com o uso do sildenafil oral no tratamento de pacientes com hipertensão arterial pulmonar idiopática grave em classe funcional III e IV, sem resposta à terapia convencional e às provas de reatividade pulmonar. MÉTODO: Trata-se de estudo prospectivo, tipo de série de casos em que seis pacientes com diagnóstico de hipertensão arterial pulmonar idiopática foram tratados com sildenafil oral, com doses de 2 a 8 mg/kg/dia, divididas em quatro a seis vezes. Os pacientes foram submetidos a exame clínico, eletrocardiograma, ecocardiograma, tomografia do tórax, cintilografia de perfusão e ventilação pulmonar, estudos da coagulação, pesquisa de esquistossomose, doença do colágeno e de síndrome de imunodeficiência adquirida para afastar causas secundárias de hipertensão pulmonar. Todos os pacientes foram submetidos a cateterismo cardíaco para a realização das provas de reatividade pulmonar com óxido nítrico, O2 a 100% e nifedipina oral e ao teste de caminhada de 6 minutos nos pacientes em condições de realizá-lo. RESULTADOS: Todos eles apresentaram boa resposta, traduzida por melhora de, pelo menos, uma classe funcional, aumento da saturação sistêmica. Cinco pacientes apresentaram diminuição da relação da pressão sistólica pulmonar/pressão sistólica sistêmica e aumento da distância percorrida no teste de caminhada nos que a realizaram. Não foram observados efeitos colaterais em um tempo de seguimento de 4 a 36 meses. Um paciente apresentou morte súbita após a suspensão do medicamento. CONCLUSÕES: Os resultados sugerem que o sildenafil possa ser uma droga promissora no tratamento dos pacientes com hipertensão pulmonar idiopática, os quais devem ser conscientizados do risco da suspensão da medicação sem orientação médica.OBJECTIVE: This study aims to provide data on the use of oral sildenafil in patients in New York Heart Association

  15. Determination of sildenafil by preconcentration on surfactant coated polymeric resin followed by spectrofluorimetry

    Directory of Open Access Journals (Sweden)

    Chien C. Wang

    2013-06-01

    Full Text Available The illicit addition of phosphodiesterase type-5 (PDE-5 inhibitors like sildenafil (Viagra in product offered as herbal medicine or dietary supplement for male erectile dysfunction has concerned authorities in recent times. In this paper, we proposed a sensitive surfactant-coated Amberlite XAD™ resin for sildenafil preconcentration method with spectrofluorimetric detection. Retention capacity of micellar coated XAD resin for sildenafil was studied and the obtained eluate was measured by spectrofluorometer at excitation and emission wavelengths of 350 and 430nm, respectively. This method allowed the detection of sildenafil at 0.15ng/mL with linear range of 0.0003–7.0μg/mL. The method has been successfully applied to the analysis of some local commercially available herbal medicines and urine. Keywords: Sildenafil, Herbal medicines, Spectrofluorimetric analysis, Surfactant

  16. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    International Nuclear Information System (INIS)

    Cora, L A; Andreis, U; Romeiro, F G; Americo, M F; Oliveira, R B; Baffa, O; Miranda, J R A

    2005-01-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t 50 ) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process

  17. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Energy Technology Data Exchange (ETDEWEB)

    Cora, L A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Andreis, U [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Romeiro, F G [Departamento de ClInica Medica, FMB, UNESP, Botucatu, SP (Brazil); Americo, M F [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Oliveira, R B [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Baffa, O [Departamento de Fisica e Matematica, FFCLRP, USP, Ribeirao Preto, SP (Brazil); Miranda, J R A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil)

    2005-12-07

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t{sub 50}) and occurred in a short time interval (1.1 {+-} 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  18. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Science.gov (United States)

    Corá, L. A.; Andreis, U.; Romeiro, F. G.; Américo, M. F.; Oliveira, R. B.; Baffa, O.; Miranda, J. R. A.

    2005-12-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t50) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  19. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

    Directory of Open Access Journals (Sweden)

    Lynch Tadhg

    2009-04-01

    Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  20. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

    LENUS (Irish Health Repository)

    Maharaj, Chrisen H

    2009-01-01

    OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  1. Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients.

    Science.gov (United States)

    Kniotek, Monika; Boguska, Agnieszka

    2017-01-01

    Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system.

  2. Resposta pressórica de pacientes com miocardiopatia chagásica ante o uso do sildenafil Pressure response in chagasic cardiomyopathy patients after using sildenafil

    Directory of Open Access Journals (Sweden)

    Rodrigo Abensur Athanazio

    2007-03-01

    Full Text Available OBJETIVO: Verificar o efeito do sildenafil na pressão arterial (PA e freqüência cardíaca (FC de indivíduos portadores de miocardiopata chagásica (MCC e de disfunção ventricular sistólica grave (FEOBJECTIVE: To accurately verify the effect of Sildenafil on blood pressure (BP and heart rate (HR in individuals with Chagasic myocardiopathy (CMC and severe systolic ventricular dysfunction (EF<40% submitted to physical activity. METHODS: Twelve men with ejection fractions <40% and CMC confirmed by a serological test were assessed. The six-minute walk test (6MWT was performed before and after administration of 50 mg of Sildenafil, with a 30 minute interval. Heart rate (HR, systolic blood pressure (SBP and diastolic blood pressure were taken and compared before and after each 6MWT. For statistical analysis purposes, the study was divided into four stages: before the 6MWT and administration of Sildenafil (S1; after the 6MWT but before the administration of Sildenafil (S2; after the administration of Sildenafil but before the 6MWT (S3; and after the administration of Sildenafil and the 6MWT (S4. RESULTS: Participant ages ranged from 47 to 68 years (57.6 ± 6.4. SBP and DBP after the 6MWT and the administration of Sildenafil (S4 were lower than before taking the drug (S2: 134.2 ± 15.1 versus 125.5 ± 14.0 and 88.4 ± 12.4 versus 83.0 ± 10.8, respectively. None of the patients reported any symptoms during the 6MWT. There were no differences in the distances walked during the 6MWT before or after taking Sildenafil (487.5±15.22 versus 505.3±18.45 meters, respectively-p=0.056, or in HR (before Sildenafil 75.5 ± 8.79 and 96.8 ± 10.36 bpm and after 77.1 ± 9.81 and 96.1 ± 12.97 bpm. CONCLUSION: Based on these results, it can be concluded that both prediction equations significantly overestimated HRmax measured during maximal GXT in Brazilian elderly women, a finding that may have important implications when prescribing exercise intensity for this

  3. Sildenafil Improves Erectile Function in Men with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Niloufar Samiei

    2015-06-01

    Full Text Available Background: Patients with Chronic Heart Failure (CHF have been shown to have enhanced risk of Erectile Dysfunction (ED due to low cardiac output, endothelial dysfunction, medications, co-morbid conditions, and psychogenic factors. Objectives: The present study aimed to evaluate the effects of sildenafil on erectile function of patients with stable CHF using the abridged 5-item version of the International Index of Erectile Function (IIEF-5. Patients and Methods: Using convenience sampling, 222 sexually-active adult males with NYHA class I-III stable CHF were included in this cross-sectional study. All the patients filled out the IIEF-5 questionnaire, in which they were required to score the five domains of male sexual function, including erectile function, orgasm function, sexual desire, intercourse satisfaction, and overall satisfaction. All the analyses were performed using the SPSS statistical software (v. 19 and P < 0.05 was considered as statistically significant. Results: In our sample, the patients’ mean age was 47.14 ± 11.86 years, their mean left ventricular ejection fraction was 20% (15% - 25%, and the prevalence of ED was 70.3%. In addition, severe, moderate, mild to moderate, and mild ED were seen in 57%, 17%, 7%, and 19% of the patients with ED, respectively. ED was significantly more prevalent in the patients with ischemic heart failure compared to those with idiopathic dilated cardiomyopathy (84.68% vs. 55.85%, P < 0.001. Moreover, the prevalence of ED was significantly lower in the patients taking sildenafil compared to the other group (42.85% vs. 82.89%, P < 0.001. Conclusions: Sildenafil appears to provide satisfactory results toward improving sexual function in patients with CHF.

  4. Gastro Hepatic Protective Effects of Sildenafil in γ-Irradiated Rats

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Salama, S.F.

    2013-01-01

    Sildenafil is a potent specific inhibitor of phosphodiesterase-5 (PDE-5), which ultimately increases intracellular cyclic guanosine monophosphate (cGMP) . Sildenafil commercially named Viagra; was studied for its gastro hepatic protective activity through acute exposure of rats to γ-rays. The experimental groups of rats were: Sildenafil [1 mg/ kg, intra venous (i.v.), in 0.2 ml saline] / day for 5 days and then exposed to 6 Gy γ-rays after 1 h of the last injection (sildenafil+ γ-rays group). Controls received saline as a vehicle/ for 5 day; sildenafil group received drug alone for 5 days, and γ-rays group received saline (without drug) for 5 days and exposed to 6 Gy γ-rays after 1 h of the last injection. All groups were decapitated on the 6th day. Gamma rays increased the level of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO) but, lowered the levels of nitric oxide (NO) and reduced glutathione (GSH) as well as lowering the activities of superoxide dismutase (SOD) and catalase (CAT) in both stomach and hepatic tissues. Sildenafil administrated before γ-rays significantly reduced the level of MDA and the activity of MPO while elevating levels of NO and GSH plus activities of SOD and CAT in both stomach and hepatic tissues compared to control and sildenafil groups. Conclusion: The data reveals that sildenafil pre-treatment has a protective effect against γ-rays-induced gastro hepatic dysfunction and supports the possible use of sildenafil as a protective agent in γ-irradiated rats

  5. Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction

    DEFF Research Database (Denmark)

    Andersen, Mads J; Ersbøll, Mads; Axelsson, Anna

    2013-01-01

    with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9......, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged...

  6. Tunnel disintegration and neutron emission probability

    International Nuclear Information System (INIS)

    Tani, Toyu; Kobayashi, Yukio.

    1993-01-01

    It is shown that the main features of the so-called cold fusion, that is, poor reproducibility, high t/n ratio and the energy spectrum of neutrons, can be explained by the 'tunnel disintegration' of a deuterium and the subsequent 'dipole disintegration' of a deuteron. Especially, the 2.45-MeV peak found in the energy spectrum, which has been considered to be owing to the d-d nuclear fusion, is explained by this mechanism, and therefore the observation of 2.45-MeV neutrons may not be a direct verification of the d-d nuclear fusion. (author)

  7. Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene–polypropylene block copolymer for maximized disintegration and dissolution

    Directory of Open Access Journals (Sweden)

    Balata GF

    2016-10-01

    Full Text Available Gehan F Balata,1,2 Ahmad S Zidan,2 Mohamad AS Abourehab,1,3 Ebtessam A Essa4 1Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, 3Department of Pharmaceutics, Faculty of Pharmacy, El-Minia University, El-Minia, 4Department of Pharmaceutics, Faculty of Pharmacy, Tanta University, Tanta, Egypt Abstract: The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188 was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs. Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by

  8. Effect of sildenafil citrate (Viagra) on coronary flow in normal subjects.

    Science.gov (United States)

    Ishikura, Fuminobu; Beppu, Shintaro; Ueda, Hiroaki; Nehra, Ajay; Khandheria, Bijoy K

    2008-01-01

    The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects.

  9. Sildenafil and retinopathy of prematurity risk in very low birth weight infants

    NARCIS (Netherlands)

    S. Samiee-Zafarghandy; J.N. van den Anker (John); M. Laughon (Matthew); R.H. Clark; P.B. Smith; C.P. Hornik

    2016-01-01

    textabstractObjective: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. Study Design: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care

  10. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans....... METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  11. SILDENAFIL CITRATE INDUCED RETINAL TOXICITY-ELECTRORETINOGRAM, OPTICAL COHERENCE TOMOGRAPHY, AND ADAPTIVE OPTICS FINDINGS.

    Science.gov (United States)

    Yanoga, Fatoumata; Gentile, Ronald C; Chui, Toco Y P; Freund, K Bailey; Fell, Millie; Dolz-Marco, Rosa; Rosen, Richard B

    2018-02-27

    To report a case of persistent retinal toxicity associated with a high dose of sildenafil citrate intake. Single retrospective case report. A 31-year-old white man with no medical history presented with complaints of bilateral multicolored photopsias and erythropsia (red-tinted vision), shortly after taking sildenafil citrate-purchased through the internet. Patient was found to have cone photoreceptor damage, demonstrated using electroretinogram, optical coherence tomography, and adaptive optics imaging. The patient's symptoms and the photoreceptor structural changes persisted for several months. Sildenafil citrate is a widely used erectile dysfunction medication that is typically associated with transient visual symptoms in normal dosage. At high dosage, sildenafil citrate can lead to persistent retinal toxicity in certain individuals.

  12. Disintegration impact on sludge digestion process.

    Science.gov (United States)

    Dauknys, Regimantas; Rimeika, Mindaugas; Jankeliūnaitė, Eglė; Mažeikienė, Aušra

    2016-11-01

    The anaerobic sludge digestion is a widely used method for sludge stabilization in wastewater treatment plant. This process can be improved by applying the sludge disintegration methods. As the sludge disintegration is not investigated enough, an analysis of how the application of thermal hydrolysis affects the sludge digestion process based on full-scale data was conducted. The results showed that the maximum volatile suspended solids (VSS) destruction reached the value of 65% independently on the application of thermal hydrolysis. The average VSS destruction increased by 14% when thermal hydrolysis was applied. In order to have the maximum VSS reduction and biogas production, it is recommended to keep the maximum defined VSS loading of 5.7 kg VSS/m(3)/d when the thermal hydrolysis is applied and to keep the VSS loading between 2.1-2.4 kg VSS/m(3)/d when the disintegration of sludge is not applied. The application of thermal hydrolysis leads to an approximately 2.5 times higher VSS loading maintenance comparing VSS loading without the disintegration; therefore, digesters with 1.8 times smaller volume is required.

  13. ( Phaseolus lunatus ) starch as a tablet disintegrant

    African Journals Online (AJOL)

    ) was evaluated. The starch from the seeds was extracted and its disintegrant ability was compared with that of maize starch BP in paracetamol based tablets at concentrations of 0, 2.5, 5, 7.5 and 10 %w/w. The following properties of the starch ...

  14. EVALUATION OF DISINTEGRANT PROPERTIES OF Neorautanenia ...

    African Journals Online (AJOL)

    Mrs. Olayemi

    of Neorautanenia mitis starch (NMS) as a disintegrant in tablet formulation. Its physicochemical ... starch had lower swelling power than maize or potato starch and when .... ejection of the tablets, they were stored over silica gel for 24 h to allow ...

  15. Evaluation of tablet disintegrant properties of microcrystalline ...

    African Journals Online (AJOL)

    This study was aimed at exploring the application of microcrystalline cellulose from cassava fermentation waste as a disintegrant in the formulation of paracetamol tablets for immediate release. Alkali delignification of the dried cassava fermentation fibres, followed by bleaching and acid depolymerisation was employed in ...

  16. Mild disintegration of green microalgae and macroalgae

    NARCIS (Netherlands)

    Postma, Richard

    2016-01-01

    An increased worldwide protein demand for food and feed and the necessity to release the water soluble proteins in the first stage of the cascade biorefinery require the development of mild protein extraction technologies. Cell disintegration is the first hurdle and is considered as one of the

  17. Neuroimaging Cerebrovascular Function and Diffuse Axonal Injury after Traumatic Brain Injury and Response to Sildenafil Treatment

    Science.gov (United States)

    2016-04-05

    n=4, FPI+sildenafil n=3). No significant main effect of either injury or treatment was observed (data not shown). Water Maze Animals in all groups...spent in prior quadrant on trial one of test day revealed no significant main effect of either injury or treatment . 41 Figure 15. Water ...injury with sildenafil treatment (each pɘ.0001). Error bars represent SEM. 50 Analysis of mean diffusivity in grey matter ROIs

  18. Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

    DEFF Research Database (Denmark)

    Clemmesen, J.O.; Giraldi, A.; Ott, P.

    2008-01-01

    AIM: To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liv...... type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG Udgivelsesdato: 2008/10/28...

  19. Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

    DEFF Research Database (Denmark)

    Clemmesen, Jens-Otto; Giraldi, Annamaria; Ott, Peter

    2008-01-01

    AIM: To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liv...... type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG....

  20. Concentration-dependent Sildenafil citrate (Viagra) effects on ROS production, energy status, and human sperm function.

    Science.gov (United States)

    Sousa, Maria Inês; Amaral, Sandra; Tavares, Renata Santos; Paiva, Carla; Ramalho-Santos, João

    2014-04-01

    Literature regarding the effects of sildenafil citrate on sperm function remains controversial. In the present study, we specifically wanted to determine if mitochondrial dysfunction, namely membrane potential, reactive oxygen species production, and changes in energy content, are involved in in vitro sildenafil-induced alterations of human sperm function. Sperm samples of healthy men were incubated in the presence of 0.03, 0.3, and 3 μM sildenafil citrate in a phosphate buffered saline (PBS)-based medium for 2, 3, 12, and 24 hours. Sperm motility and viability were evaluated and mitochondrial function, i.e., mitochondrial membrane potential and mitochondrial superoxide production were assessed using flow-cytometry. Additionally, adenosine triphosphate (ATP) levels were determined by high performance liquid chromatography (HPLC) analysis. Results show a decrease in sperm motility correlated with the level of mitochondria-generated superoxide, without a visible effect on mitochondrial membrane potential or viability upon exposure to sildenafil. The effect on both motility and superoxide production was higher for the intermediate concentration of sildenafil (0.3 µM) indicating that the in vitro effects of sildenafil on human sperm do not vary linearly with drug concentration. Adenosine triphosphate levels also decreased following sildenafil exposure, but this decrease was only detected after a decrease in motility was already evident. These results suggest that along with the level of ATP and mitochondrial function other factors are involved in the early sildenafil-mediated decline in sperm motility. However, the further decrease in ATP levels and increase in mitochondria-generated reactive oxygen species after 24 hours of exposure might further contribute towards declining sperm motility.

  1. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  2. A Case of Recurrent Transient Monocular Visual Loss after Receiving Sildenafil

    Directory of Open Access Journals (Sweden)

    Asaad Ghanem Ghanem

    2011-01-01

    Full Text Available A 53-year-old man was attended to the Clinic Ophthalmic Center, Mansoura University, Egypt, with recurrent transient monocular visual loss after receiving sildenafil citrate (Viagra for erectile dysfunction. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral nonarteritic anterior ischemic optic neuropathy (NAION. Physicians might look for arteriosclerotic risk factors and family history of NAION among predisposing risk factors before prescribing sildenafil erectile dysfunction drugs.

  3. Increased collagen maturity with sildenafil citrate: experimental high risk colonic anastomosis model.

    Science.gov (United States)

    Cakir, Tebessum; Ozer, Ilter; Bostanci, Erdal Birol; Keklik, Tulay Timucin; Ercin, Ugur; Bilgihan, Ayse; Akoglu, Musa

    2015-01-01

    Inadequate healing and high anastomosis leak rates at rectal anastomosis may be due to lack of supportive serosal layer and technical difficulty of low anterior resections. Positive effects of sildenafil on wound healing were observed. The aim of this study was to simulate rectal anastomosis as a technical insufficient anastomosis and investigate the effects of sildenafil on anastomosis healing. Colonic anastomoses were carried out in 64 rats and randomized into four groups, CA-S, complete anastomoses without sildenafil (10 mg/kg for 5 days); CA+S, complete anastomoses with sildenafil; IA-S, incomplete anastomoses without sildenafil; IA+S, incomplete anastomoses with sildenafil. Half of the rats in every group were sacrificed on post-operative day (POD) 3, half of them sacrificed on POD 7. Tissues from the anastomoses were used for functional, histochemical, biochemical investigations. Sildenafil treatment resulted in increased bursting pressures in IA+S on POD 7 (p=0.010). Collagen maturity was higher in IA+S on POD 3 and POD 7, CA+S on POD 7 (p=0.010; p=0.010; p<0.007). Collagen content was higher in IA+S on POD 7 (p<0.001). Glutathione, hydroxyproline levels were similar. Malondialdehyde levels were lower in IA+S on POD 3 (p<0.001). Epithelization score was higher in IA+S on POD 7 (p=0.007). Inflammation score was higher in CA-S group on POD 3 and POD 7 (p<0.001; p<0.001). Neutrophil score was lower in CA+S on POD 3 (p=0.005). An increase in collagen content, maturity, and epithelization, a decrease in neutrophil infiltration, oxidative stress and better mechanical strength were observed with the administration of sildenafil. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

  5. Childhood Disintegrative Disorder as a Complication of Chicken Pox.

    Science.gov (United States)

    Verma, Jitendra Kumar; Mohapatra, Satyakam

    2016-01-01

    Childhood disintegrative disorder (CDD) is characterized by late onset (>3 years of age) of developmental delays in language, social function and motor skills. Commonly there is no antecedent physical disorder leading to childhood disintegrative disorder. The present case report describes a child who developed childhood disintegrative disorder at the age of 6 years after an episode of chicken pox.

  6. In vitro models for the prediction of in vivo performance of oral dosage forms

    NARCIS (Netherlands)

    Kostewicz, E.S.; Abrahamsson, B.; Brewster, M.; Brouwers, J.; Butler, J.; Carlert, S.; Dickinson, P.A.; Dressman, J.; Holm, R.; Klein, S.; Mann, J.; McAllister, M.; Minekus, M.; Muenster, U.; Müllertz, A.; Verwei, M.; Vertzoni, M.; Weitschies, W.; Augustijns, P.

    2014-01-01

    Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection

  7. Effects of ultrasonic disintegration of excess sludge obtained in disintegrators of different constructions.

    Science.gov (United States)

    Zielewicz, Ewa; Tytła, Malwina

    2015-01-01

    The ultrasonic disintegration of excess sludge is placed after the mechanical thickening but before the digestion tanks in order to intensify the process of sludge stabilization. The effects obtained directly after ultrasonic disintegration depend on many factors and can be grouped in two main categories: factors affecting the quality of sludge and those associated with the construction of disintegrators and its parameters. The ultrasonic disintegration research was carried out using three types of structural solutions of disintegrators. Two of them, that is, WK-2000 ultrasonic generator (P = 400 W) working with a thin sonotrode and WK-2010 ultrasonic generator (P = 100-1000 W) working with a new type construction emitter lens sonotrode, were compared with the influence of a washer with a flat emitter. The investigations have shown that in the same sludge, using the same value of volumetric energy, the resulting effect depends on the construction of the ultrasonic disintegrator, that is, design of the head and the ratio between the field of the emitter and the field of the chamber in sonicated medium.

  8. Effects of disintegration-promoting agent, lubricants and moisture treatment on optimized fast disintegrating tablets.

    Science.gov (United States)

    Late, Sameer G; Yu, Yi-Ying; Banga, Ajay K

    2009-01-05

    Effects of calcium silicate (disintegration-promoting agent) and various lubricants on an optimized beta-cyclodextrin-based fast-disintegrating tablet formulation were investigated. Effects of moisture treatment were also evaluated at 75, 85 and 95% relative humidities. A two factor, three levels (3(2)) full factorial design was used to optimize concentrations of calcium silicate and lubricant. Magnesium stearate, being commonly used lubricant, was used to optimize lubricant concentration in optimization study. Other lubricants were evaluated at an obtained optimum concentration. Desiccator with saturated salt solutions was used to analyze effects of moisture treatments. Results of multiple linear regression analysis revealed that concentration of calcium silicate had no effect; however concentration of lubricant was found to be important for tablet disintegration and hardness. An optimized value of 1.5% of magnesium stearate gave disintegration time of 23.4 s and hardness of 1.42 kg. At an optimized concentration, glycerol dibehenate and L-leucine significantly affected disintegration time, while talc and stearic acid had no significant effect. Tablet hardness was significantly affected with L-leucine, while other lubricants had no significant effect. Hardness was not affected at 75% moisture treatment. Moisture treatment at 85 and 95% increased hardness of the tablets; however at the same time it negatively affected the disintegration time.

  9. Development and Evaluation of Orally Disintegrating Tablets of ...

    African Journals Online (AJOL)

    ... crospovidone and magnesium stearate as key excipients, and with cherry flavor and aspartame as flavor and sweetener, respectively. These formulations were then evaluated using pharmacopoeial and non-pharmacopoeial physical and chemical tests. Dissolution and assay tests were performed using USP apparatus II ...

  10. Development of Oral Fast-Disintegrating Levothyroxine Films for ...

    African Journals Online (AJOL)

    physical appearance, thickness, weight variation, folding endurance, drug content uniformity, The effect ... In children, hypothyroidism leads to delay in growth and .... rapid and convenient drug delivery technology for the pediatric patients. Table 3: Physical characteristics of films. Batch. Drug content. (%). Folding endurance.

  11. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    International Nuclear Information System (INIS)

    Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

    2013-01-01

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

  12. Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach.

    Science.gov (United States)

    Desai, Parind Mahendrakumar; Er, Patrick Xuan Hua; Liew, Celine Valeria; Heng, Paul Wan Sia

    2014-10-01

    Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.

  13. Probable neuro sexual mode of action of Casimiroa edulis seed extract versus [correction of verses] sildenafil citrate (Viagra(tm)) on mating behavior in normal male rats.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2008-01-01

    The present study deals with the aphrodisiac actions of the aqueous extract of the seeds of the hypotensive plant Casimiroa edulis on the sexual behavior of normal male rats. In this investigation 30 healthy male Wister strain white albino rats showing the brisk sexual activity age 15 weeks, weighing 400-450 grams were included. Female rats were artificially brought into estrous by hormonal treatment. Receptivity was checked by exposing them to the male rats and the most receptive females were selected for the stud The mating responses including Mounting Frequency (MF), Intromission Frequency (IF), Mounting Latency (ML), Intromission Latency (IL), Ejaculatory Latency in first and second series (EL1 and EL2) and Post Ejaculatory Interval (PEI) were recorded after treating the animals with 250 mg/kg casimiroa edulis extract (test reference) and 5 mg/kg sildenafil citrate (standard reference) respectively orally per day for 7 days. Both the groups exhibited a significant increase in Mounting Frequency, Intromission Frequency, and first and second ejaculatory latencies, where as Mounting and Intromission latencies and the Post Ejaculatory Interval showed a significant reduction than the controls. Although a similar pattern of mating behavior was observed among the test and the standard groups, however in all the cases as expected, sildenafil produced greater activity than the casimiroa edulis extract. These results suggest the possibility of a similar mode of action of casimiroa edulis and sildenafil citrate on mating behavior in these animals. Our work reported in this research thus provide preliminary evidence that the aqueous seed extract of casimiroa edulis possesses alphrodisiac activity and may be used as an alternative drug therapy to restore sexual functions probably via a neurogenic mode of action.

  14. Theory of positive disintegration as a model of adolescent development.

    Science.gov (United States)

    Laycraft, Krystyna

    2011-01-01

    This article introduces a conceptual model of the adolescent development based on the theory of positive disintegration combined with theory of self-organization. Dabrowski's theory of positive disintegration, which was created almost a half century ago, still attracts psychologists' and educators' attention, and is extensively applied into studies of gifted and talented people. The positive disintegration is the mental development described by the process of transition from lower to higher levels of mental life and stimulated by tension, inner conflict, and anxiety. This process can be modeled by a sequence of patterns of organization (attractors) as a developmental potential (a control parameter) changes. Three levels of disintegration (unilevel disintegration, spontaneous multilevel disintegration, and organized multilevel disintegration) are analyzed in detail and it is proposed that they represent behaviour of early, middle and late periods of adolescence. In the discussion, recent research on the adolescent brain development is included.

  15. Mechanism of disintegrant action of polacrilin potassium: Swelling or wicking?

    Directory of Open Access Journals (Sweden)

    Mrudula Hemant Bele

    2012-02-01

    Full Text Available The effect of particle size, pH of medium, and presence of lubricant on the swelling behaviour, water uptake properties and disintegrant performance of polacrilin potassium was examined. Particle size did not affect the bulk swelling of disintegrant particles when measured as settling volume, but increased the water uptake and decreased the disintegration time of tablets containing this disintegrant. An increase in the pH of the medium from acidic to neutral increased the bulk swelling of the particles, whereas it decreased water uptake and disintegrant performance. Addition of lubricant had no effect on settling volume, but decreased the water uptake rate and the disintegrant performance significantly. It is concluded that wicking, i.e. capillary action, rather than swelling, is the major factor that contributes to the disintegration behaviour of polacrilin potassium.

  16. Internet-ordered viagra (sildenafil citrate) is rarely genuine.

    Science.gov (United States)

    Campbell, Neil; Clark, John P; Stecher, Vera J; Goldstein, Irwin

    2012-11-01

    Counterfeit medication is a growing problem. This study assessed the requirement for prescription, cost, origin, and content of medications sold via the Internet and purporting to be the phosphodiesterase type 5 inhibitor Viagra (sildenafil citrate). Pfizer monitored top search results for the query "buy Viagra" on the two leading Internet search engines in March 2011. Orders were placed from 22 unique Web sites claiming to sell Viagra manufactured by Pfizer. Tablets received were assessed for chemical composition. No Web site examined required a prescription for purchase or a health screening survey; 90% offered illegal "generic Viagra." Cost per tablet ranged from $3.28-$33.00. Shipment origins of purchases were Hong Kong (N = 11), the United States (N = 6), and the United Kingdom (N = 2) as well as Canada, China, and India (N = 1 each). Notably, the four Internet pharmacies claiming to be Canadian did not ship medication from a Canadian address. Of 22 sample tablets examined, 17 (77%) were counterfeit, 4 (18%) were authentic, and 1 (5%) was an illegal generic. Counterfeit tablets were analyzed for sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra, and contents varied between 30% and 50% of the label claim. Counterfeits lacked product information leaflets, including appropriate safety warnings, and genuine Viagra formulations. Internet sites claiming to sell authentic Viagra shipped counterfeit medication 77% of the time; counterfeits usually came from non-U.S. addresses and had 30% to 50% of the labeled API claim. Caution is warranted when purchasing Viagra via the Internet. © 2012 International Society for Sexual Medicine.

  17. Resolução do "shunt" direita-esquerda após uso do sildenafil como tratamento de hipertensão pulmonar primária

    Directory of Open Access Journals (Sweden)

    Silva Sérgio Marques da

    2003-01-01

    Full Text Available Hipertensão pulmonar primária é uma doença rara, progressiva e com alta mortalidade, cujo tratamento baseia-se em medicações de alto custo e pouco disponíveis em nosso meio. O sildenafil é um vasodilatador de fácil administração por via oral, com indicação primária para disfunção erétil e que recentemente tem sido descrito como opção terapêutica para a hipertensão pulmonar primária. Relata-se o caso de uma paciente de 21 anos com diagnóstico de hipertensão pulmonar primária, que apresentou piora abrupta da saturação de oxigênio, com abertura do forame oval e shunt direita-esquerda, evidenciados ao ecocardiograma. Foi introduzido sildenafil na dose de 225mg/dia com melhora progressiva da oxigenação e reversão do shunt após 40 dias. Os autores acreditam que o sildenafil seja uma opção no tratamento da hipertensão pulmonar primária, embora estudos clínicos que comprovem sua segurança e eficácia ainda sejam necessários.

  18. Formation of disintegration particles in spacecraft recorders

    International Nuclear Information System (INIS)

    Kurnosova, L.V.; Fradkin, M.I.; Razorenov, L.A.

    1986-01-01

    Experiments performed on the spacecraft Salyut 1, Kosmos 410, and Kosmos 443 enable us to record the disintegration products of particles which are formed in the material of the detectors on board the spacecraft. The observations were made by means of a delayed coincidence method. We have detected a meson component and also a component which is apparently associated with the generation of radioactive isotopes in the detectors

  19. Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

    Directory of Open Access Journals (Sweden)

    Denilson C. Albuquerque

    2005-08-01

    Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

  20. Sildenafil (Viagra(®)) prevents and restores LPS-induced inflammation in astrocytes.

    Science.gov (United States)

    de Santana Nunes, Ana Karolina; Rapôso, Catarina; Björklund, Ulrika; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves; Hansson, Elisabeth

    2016-09-06

    Astrocytes are effectively involved in the pathophysiological processes in the central nervous system (CNS) and may contribute to or protect against development of inflammatory and degenerative diseases. Sildenafil is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor, which induces cyclic GMP accumulation. However, the mechanisms of actions on glial cells are not clear. The aim of the present work is to evaluate the role of sildenafil in lipopolysaccharide (LPS)-stimulated astrocytes. The cytoskeleton integrity and Ca(2+) waves were assessed as indicators of inflammatory state. Two main groups were done: (A) one prevention and (B) one restoration. Each of these groups: A1: control; A2: LPS for 24h; A3: sildenafil 1 or 10μM for 4h and then sildenafil 1 or 10μM+LPS for 24h. B1: control; B2: LPS for 24h; B3: LPS for 24h and then LPS+sildenafil 1 or 10μM for 24h. Cytoskeleton integrity was analyzed through GFAP immunolabeling and actin labeling with an Alexa 488-conjugated phalloidin probe. Calcium responses were assessed through a Ca(2+)-sensitive fluorophore Fura-2/AM. The results show that both preventive and restorative treatments with sildenafil (in both concentrations) reduced the Ca(2+) responses in intensity and induced a more organized actin fiber pattern, compared to LPS treated cells. This work demonstrated for the first time that astrocytes are a key part of the sildenafil protective effects in the CNS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Sildenafil delays the intestinal transit of a liquid meal in awake rats

    Directory of Open Access Journals (Sweden)

    J.R.V Graça

    2008-01-01

    Full Text Available Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44 were treated (0.2 mL, iv with sildenafil (4 mg/kg or vehicle (0.01 N HCl. Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP was monitored in a separate group of rats (N = 14. Data (medians within interquartile ranges were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6 vs 2.9 (2.7-3.1; 3.8 (3.4-4.0 vs 2.9 (2.5-3.1, and 4.3 (3.9-4.5 vs 3.4 (3.2-3.7, respectively; P < 0.05. MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05 within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

  2. Sewage sludge disintegration by high-pressure homogenization: a sludge disintegration model.

    Science.gov (United States)

    Zhang, Yuxuan; Zhang, Panyue; Ma, Boqiang; Wu, Hao; Zhang, Sheng; Xu, Xin

    2012-01-01

    High-pressure homogenization (HPH) technology was applied as a pretreatment to disintegrate sewage sludge. The effects of homogenization pressure, homogenization cycle number, and total solid content on sludge disintegration were investigated. The sludge disintegration degree (DD(COD)), protein concentration, and polysaccharide concentration increased with the increase of homogenization pressure and homogenization cycle number, and decreased with the increase of sludge total solid (TS) content. The maximum DD(COD) of 43.94% was achieved at 80 MPa with four homogenization cycles for a 9.58 g/L TS sludge sample. A HPH sludge disintegration model of DD(COD) = kNaPb was established by multivariable linear regression to quantify the effects of homogenization parameters. The homogenization cycle exponent a and homogenization pressure exponent b were 0.4763 and 0.7324 respectively, showing that the effect of homogenization pressure (P) was more significant than that of homogenization cycle number (N). The value of the rate constant k decreased with the increase of sludge total solid content. The specific energy consumption increased with the increment of sludge disintegration efficiency. Lower specific energy consumption was required for higher total solid content sludge.

  3. Reduction of excess sludge production using mechanical disintegration devices.

    Science.gov (United States)

    Strünkmann, G W; Müller, J A; Albert, F; Schwedes, J

    2006-01-01

    The usability of mechanical disintegration techniques for the reduction of excess sludge production in the activated sludge process was investigated. Using three different disintegration devices (ultrasonic homogeniser, stirred media mill, high pressure homogeniser) and different operational parameters of the disintegration, the effect of mechanical disintegration on the excess sludge production and on the effluent quality was studied within a continuously operated, laboratory scale wastewater treatment system with pre-denitrification. Depending on the operational conditions and the disintegration device used, a reduction of excess sludge production of up to 70% was achieved. A combination of mechanical disintegration with a membrane bioreactor process with high sludge age is more energy effective concerning reduction of sludge production than with a conventional activated sludge process at lower sludge ages. Depending on the disintegration parameters, the disintegration has no, or only minor, negative effect on the soluble effluent COD and on the COD-removal capacity of the activated sludge process. Nitrogen-removal was slightly deteriorated by the disintegration, whereas the system used was not optimised for nitrogen removal before disintegration was implemented.

  4. Modes of Disintegration of Solid Foods in Simulated Gastric Environment

    Science.gov (United States)

    Kong, Fanbin

    2009-01-01

    A model stomach system was used to investigate disintegration of various foods in simulated gastric environment. Food disintegration modes and typical disintegration profiles are summarized in this paper. Mechanisms contributing to the disintegration kinetics of different foods were investigated as related to acidity, temperature, and enzymatic effect on the texture and changes in microstructure. Food disintegration was dominated by either fragmentation or erosion, depending on the physical forces acting on food and the cohesive force within the food matrix. The internal cohesive forces changed during digestion as a result of water penetration and acidic and enzymatic hydrolysis. When erosion was dominant, the disintegration data (weight retention vs. disintegration time) may be expressed with exponential, sigmoidal, and delayed-sigmoidal profiles. The different profiles are the result of competition among the rates of water absorption, texture softening, and erosion. A linear-exponential equation was used to describe the different disintegration curves with good fit. Acidity and temperature of gastric juice showed a synergistic effect on carrot softening, while pepsin was the key factor in disintegrating high-protein foods. A study of the change of carrot microstructure during digestion indicated that degradation of the pectin and cell wall was responsible for texture softening that contributed to the sigmoidal profile of carrot disintegration. PMID:20401314

  5. Sildenafil protects neuronal cells from mitochondrial toxicity induced by β-amyloid peptide via ATP-sensitive K+ channels.

    Science.gov (United States)

    Son, Yonghae; Kim, Koanhoi; Cho, Hyok-Rae

    2018-06-02

    To understand the molecular mechanisms underlying the beneficial effects of sildenafil in animal models of neurological disorders, we investigated the effects of sildenafil on the mitochondrial toxicity induced by β-amyloid (Aβ) peptide. Treatment of HT-22 hippocampal neuronal cells with Aβ 25∼35 results in increased mitochondrial Ca 2+ load, which is subsequently suppressed by sildenafil as well as by diazoxide, a selective opener of the ATP-sensitive K + channels (K ATP ). However, the suppressive effects of sildenafil and diazoxide are significantly attenuated by 5-hydroxydecanoic acid (5-HD), a K ATP inhibitor. The increased mitochondrial Ca 2+ overload is accompanied by decrease in the intracellular ATP concentration, increase in intracellular ROS generation, occurrence of mitochondrial permeability transition, and activation of caspase-9 and cell death. Exposure to sildenafil inhibited the mitochondria-associated changes and cell death induced by Aβ. However, the inhibitory effects of sildenafil are abolished or weakened in the presence of 5-HD, suggesting that opening of the mitochondrial K ATP is required for sildenafil to exert these effects. Taken together, these results indicate that at the mitochondrial levels, sildenafil plays a protective role towards neuronal cell in an environment rich in Aβ, and exerts its effects via the mitochondrial K ATP channels-dependent mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Effect of Sildenafil Citrate on Intraocular Pressure and Blood Pressure in Human Volunteers

    Science.gov (United States)

    Gerometta, Rosana; Alvarez, Lawrence J.; Candia, Oscar A.

    2011-01-01

    Anecdotal reports have suggested that the vasodilator, sildenafil citrate, which evokes its effect via a select inhibition of PDE5, has the potential to increase intraocular pressure (IOP) in some individuals. An ocular hypertensive effect by sildenafil was also recently described in a sheep animal model. In contrast, clinical studies have not found a direct association between sildenafil ingestion (commonly consumed as Viagra) and changes in IOP. However, some such studies also reported no effects of sildenafil on systemic blood pressure (BP) at the time of the IOP determination. Given this surprising result, our purpose was to repeat a study in human volunteers in the city of Corrientes, Argentina to corroborate the effects of sildenafil on human IOP and systemic BP. For the present study, 9 healthy volunteers (male and female, 18 to 74 years old) were selected as subjects after ophthalmic and cardiovascular evaluation indicated that they exhibited normal parameters for their age. In a masked, placebo-controlled study, the subjects ingested 100 mg sildenafil citrate (provided as Vorst from Laboratorios Bernabo, Argentina) in one session, and a placebo on a second separate occasion. IOP was measured with a Goldman applanation tonometer by an ophthalmologist, and BP by a second physician, neither of whom witnessed the tablet ingestion by the volunteers, nor provided with information on the nature of the test compounds. A third individual administered the tablets. The average baseline IOP of this group of 9 was 13.1 ± 0.6 mm Hg. Subsequent to sildenafil ingestion, IOP increased by 26% to 16.5 ± 0.8 mm Hg 60 min later (p< 0.005, as paired data), and returned to control values within 2 hrs. Both systolic and diastolic BP were significantly reduced by sildenafil ingestion. At the point of maximal systemic hypotension (90 min), the systolic and diastolic pressures declined by 15% and 13%, respectively. No significant changes in IOP or BP were recorded after ingestion

  7. Effect of sildenafil citrate on intraocular pressure and blood pressure in human volunteers.

    Science.gov (United States)

    Gerometta, Rosana; Alvarez, Lawrence J; Candia, Oscar A

    2011-07-01

    Anecdotal reports have suggested that the vasodilator, sildenafil citrate, which evokes its effect via a select inhibition of PDE5, has the potential to increase intraocular pressure (IOP) in some individuals. An ocular hypertensive effect by sildenafil was also recently described in a sheep animal model. In contrast, clinical studies have not found a direct association between sildenafil ingestion (commonly consumed as Viagra) and changes in IOP. However, some such studies also reported no effects of sildenafil on systemic blood pressure (BP) at the time of the IOP determination. Given this surprising result, our purpose was to repeat a study in human volunteers in the city of Corrientes, Argentina to corroborate the effects of sildenafil on human IOP and systemic BP. For the present study, 9 healthy volunteers (male and female, 18-74 years old) were selected as subjects after ophthalmic and cardiovascular evaluation indicated that they exhibited normal parameters for their age. In a masked, placebo-controlled study, the subjects ingested 100 mg sildenafil citrate (provided as Vorst from Laboratorios Bernabo, Argentina) in one session, and a placebo on a second separate occasion. IOP was measured with a Goldman applanation tonometer by an ophthalmologist, and BP by a second physician, neither of whom witnessed the tablet ingestion by the volunteers, nor provided with information on the nature of the test compounds. A third individual administered the tablets. The average baseline IOP of this group of 9 was 13.1 ± 0.6 mm Hg. Subsequent to sildenafil ingestion, IOP increased by 26% to 16.5 ± 0.8 mm Hg 60 min later (P < 0.005, as paired data), and returned to control values within 2 h. Both systolic and diastolic BP were significantly reduced by sildenafil ingestion. At the point of maximal systemic hypotension (90 min), the systolic and diastolic pressures declined by 15% and 13%, respectively. No significant changes in IOP or BP were recorded after

  8. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

    Science.gov (United States)

    Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

    2009-05-01

    Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

  9. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  10. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  11. Phosphodiesterase 5 and effects of sildenafil on cerebral arteries of man and guinea pig

    DEFF Research Database (Denmark)

    Kruuse, Christina; Khurana, Tejvir S; Rybalkin, Sergei D

    2005-01-01

    and UK-114,542, and a PDE1 inhibitor UK-90,234 on cGMP hydrolysis were investigated in human and guinea pig cerebral arteries. The vasoactive responses of the compounds were evaluated in guinea pig basilar arteries in vitro, with concomitant measurements of cAMP and cGMP. PDE5 was found in human middle...... cerebral arteries. Sildenafil and UK-114,542 inhibited cGMP hydrolysis concentration-dependently in both species. In guinea pig arteries, sildenafil induced an endothelium-dependent vasodilatation only at concentrations above 10 nM, which was augmented by sodium nitroprusside and attenuated by reduction...... of cGMP, but was cGMP independent at high concentrations. UK-114,542 was more and UK-90,234 was less potent than sildenafil. In conclusion, PDE5 is present in human and guinea pig cerebral arteries, and is inhibited by sildenafil at micromolar levels. Sildenafil in vitro is a poor dilator of guinea pig...

  12. Patient preference and satisfaction in erectile dysfunction therapy: a comparison of the three phosphodiesterase-5 inhibitors sildenafil, vardenafil and tadalafil

    Directory of Open Access Journals (Sweden)

    Amr Abdel Raheem

    2009-04-01

    Full Text Available Amr Abdel Raheem1, Philip Kell21St. Peter’s Andrology Department, The Institute of Urology, London, and Cairo University, Egypt; 2St. Peter’s Andrology Department, The Institute of Urology, London, UKAbstract: Erectile dysfunction (ED is a problem that may affect up to 52% of men between the ages of 40 and 70. It can be distressing because of its negative effect on self-esteem, quality of life, and interpersonal relationships. Oral phosphodiesterase-5 inhibitors (PDE5 inhibitors are now the first choice of treatment in ED. The availability of three (sildenafil citrate, tadalafil, and vardenafil well tolerated and effective oral PDE5 inhibitors gives treatment options for men with ED. Although the mechanism of action is the same for the three drugs, they differ in their pharmacokinetics. Several preference studies were conducted between the three PDE5 inhibitors but they were not free from bias. Because of the lack of overwhelming reliable data showing that one PDE5 inhibitor is superior to another, current opinion is that the individual patient should have the opportunity to test all three drugs and then select the one that best suits him and his partner.Keywords: erectile dysfunction, PDE5 inhibitors, patient preference

  13. Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet.

    Science.gov (United States)

    Jung, Huijeong Ashley; Augsburger, Larry L

    2012-07-01

    An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab® concentration, DiPac®/Xylitab® ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab® and/or Xylitab®, magnesium stearate, and Explotab® suggested that the amount of Explotab® was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel® and Explotab®, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone® XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol® showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.

  14. Biohydrogen production using waste activated sludge disintegrated by gamma irradiation

    International Nuclear Information System (INIS)

    Yin, Yanan; Wang, Jianlong

    2015-01-01

    Highlights: • The waste activated sludge could be disintegrated by gamma irradiation. • The disintegrated sludge could be used for biohydrogen production. • Combined alkali-irradiation treatment achieved the highest solubilization of sludge. - Abstract: The biohydrogen production using the disintegrated and dissolved sludge by gamma irradiation was studied. The experimental results showed that gamma irradiation and irradiation combined with alkali pretreatment could disintegrate and dissolve waste activated sludge for biohydrogen production. The alkali-irradiation treatment of the sludge at pH = 12 and 20 kGy achieved the highest disintegration and dissolution, i.e., it could destroy the cell walls and release organic matters (such as soluble COD, polysaccharides and protein) into the solution. The disintegrated sludge could be used as a low-cost substrate for biohydrogen production

  15. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

    Science.gov (United States)

    Washington, Chad W; Derdeyn, Colin P; Dhar, Rajat; Arias, Eric J; Chicoine, Michael R; Cross, DeWitte T; Dacey, Ralph G; Han, Byung Hee; Moran, Christopher J; Rich, Keith M; Vellimana, Ananth K; Zipfel, Gregory J

    2016-02-01

    Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

  16. Numerical Simulation on Zonal Disintegration in Deep Surrounding Rock Mass

    OpenAIRE

    Xuguang Chen; Yuan Wang; Yu Mei; Xin Zhang

    2014-01-01

    Zonal disintegration have been discovered in many underground tunnels with the increasing of embedded depth. The formation mechanism of such phenomenon is difficult to explain under the framework of traditional rock mechanics, and the fractured shape and forming conditions are unclear. The numerical simulation was carried out to research the generating condition and forming process of zonal disintegration. Via comparing the results with the geomechanical model test, the zonal disintegration p...

  17. Effects of ultrasonic disintegration on sludge microbial activity and dewaterability

    International Nuclear Information System (INIS)

    Li Huan; Jin Yiying; Mahar, Rasool Bux; Wang Zhiyu; Nie Yongfeng

    2009-01-01

    Ultrasonic treatment can disintegrate sludge, enhance microbial activity and improve sludge dewaterability at different energy inputs. To find their relationship, the three phenomena during ultrasonic treatment were investigated synchronously, and an experimental model was established to describe the process of ultrasonic sludge disintegration. Analysis results showed that the changes of sludge microbial activity and dewaterability were dependent on sludge disintegration degree during ultrasonic treatment. When sludge disintegration degree was lower than 20%, sludge flocs were disintegrated into micro-floc aggregates and the microbial activity increased over 20%. When sludge disintegration degree was over 40%, most cells were destroyed at different degree, and sludge activity decreased drastically. Only when sludge disintegration degree was 2-5%, sludge dewaterability was improved with the conditioning of FeCl 3 . It was also found that the sonication with low density and long duration was more efficient than sonication with high density and short duration at the same energy input for sludge disintegration, and a transmutative power function model can be used to describe the process of ultrasonic disintegration

  18. Effects of ultrasonic disintegration on sludge microbial activity and dewaterability.

    Science.gov (United States)

    Huan, Li; Yiying, Jin; Mahar, Rasool Bux; Zhiyu, Wang; Yongfeng, Nie

    2009-01-30

    Ultrasonic treatment can disintegrate sludge, enhance microbial activity and improve sludge dewaterability at different energy inputs. To find their relationship, the three phenomena during ultrasonic treatment were investigated synchronously, and an experimental model was established to describe the process of ultrasonic sludge disintegration. Analysis results showed that the changes of sludge microbial activity and dewaterability were dependent on sludge disintegration degree during ultrasonic treatment. When sludge disintegration degree was lower than 20%, sludge flocs were disintegrated into micro-floc aggregates and the microbial activity increased over 20%. When sludge disintegration degree was over 40%, most cells were destroyed at different degree, and sludge activity decreased drastically. Only when sludge disintegration degree was 2-5%, sludge dewaterability was improved with the conditioning of FeCl(3). It was also found that the sonication with low density and long duration was more efficient than sonication with high density and short duration at the same energy input for sludge disintegration, and a transmutative power function model can be used to describe the process of ultrasonic disintegration.

  19. Characterising the disintegration properties of tablets in opaque media using texture analysis

    OpenAIRE

    Scheuerle, Rebekah L.; Gerrard, Stephen E.; Kendall, Richard A.; Tuleu, Catherine; Slater, Nigel K.H.; Mahbubani, Krishnaa T.

    2015-01-01

    Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. In this study is explored an application of texture analysis disintegration testin...

  20. Women taking the “blue pill” (sildenafil citrate: such a big deal?

    Directory of Open Access Journals (Sweden)

    Lo Monte G

    2014-11-01

    Full Text Available Giuseppe Lo Monte, Angela Graziano, Isabella Piva, Roberto Marci Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy Abstract: For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra® in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate should be kept as the last option. Keywords: phosphodiesterase type 5 inhibitors, female sexual arousal disorder (FSAD, sildenafil citrate

  1. Adsorption and inhibitive properties of sildenafil (Viagra for zinc in hydrochloric acid solution

    Directory of Open Access Journals (Sweden)

    A.S. Fouda

    Full Text Available Sildenafil (Viagra was investigated as corrosion inhibitor for Zn in 1 M HCl solution using chemical and electrochemical methods at 25 °C. Electrochemical results showed that this drug is efficient inhibitor for Zn in HCl and the inhibition efficiency (IE reached to 91% at 300 ppm. The IE increases with the drug concentration and decreases with increasing temperature. The adsorption of this drug on Zn surface follows Langmuir adsorption isotherm. The polarization plots revealed that Sildenafil acts as a mixed-type inhibitor. The thermodynamic parameters of activation and adsorption were calculated and discussed. The surface morphology of the Zn specimens was evaluated using scanning electron microscope (SEM, energy dispersive X-ray (EDX, atomic force microscopy (AFM and Fourier transform infrared spectroscopy (FTIR techniques. Keywords: Zn, Corrosion inhibition, HCl, SEM, EDX, AFM, FTIR, Sildenafil drug

  2. Deuteron photo-disintegration at large energies

    International Nuclear Information System (INIS)

    Potterveld, D.H.

    1994-01-01

    Current proposals at CEBAF include the measurement of cross sections and polarization observables of exclusive photo-reactions such as deuteron photo-disintegration and pion photo-production from nucleons. At issue is the applicability of traditional meson-exchange models versus quark models of these reactions at photon energies of several GeV. Beam energies above 4 GeV at CEBAF could make possible the measurement of these reactions over a kinematic range sufficiently broad to distinguish between the models. Estimates of counting rates for a Hall-C experiment to measure the γd → pn cross section are presented

  3. Anti-neutrino disintegration of the deuteron

    International Nuclear Information System (INIS)

    Mueller, W.; Gari, M.; Max-Planck-Institut fuer Chemie

    1981-01-01

    The anti-neutrino disintegration of the deuteron (anti ν + D → anti ν + n + p and anti νsub(e) + D → + e + + n + n) is calculated using realistic two-body states. Meson-exchange currents are considered in the one-boson-exchange limit. The results are discussed as corrections to the cross sections obtained in effective range approximations. It is shown that the ratio of the cross sections (sigma - /sigma 0 ) for reactor antineutrinos is practically independent of the nuclear physics uncertainties. (orig.)

  4. Disintegration of materials by cavitating microjets

    Directory of Open Access Journals (Sweden)

    Mlkvik M.

    2013-04-01

    Full Text Available In the paper is presented an investigation of material disintegration by cavitating microjets. Cavitating microjet develops behind the micro-orifice at high flow speeds, when local pressure drop initiates a cavitation phenomenon. Described is a method and presented are selected results of experiments. Experiments were carried out with 2 micro-orifices at different flow conditions (cavitation number, distance between sample and micro-orifice. Experiments are based on flow visualisation as well as on a character of material displacement.

  5. Disintegration of collagen fibrils by Glucono-δ-lactone: An implied lead for disintegration of fibrosis.

    Science.gov (United States)

    Jayamani, Jayaraman; Ravikanth Reddy, R; Madhan, Balaraman; Shanmugam, Ganesh

    2018-02-01

    Excess accumulation of collagen (fibrosis) undergoes self-aggregation, which leads to fibrillar collagen, on the extracellular matrix is the hallmark of a number of diseases such as keloids, hypertrophic scars, and systemic scleroderma. Direct inhibition or disintegration of collagen fibrils by small molecules offer a therapeutic approach to prevent or treat the diseases related to fibrosis. Herein, the anti-fibrotic property of Glucono-δ-lactone (GdL), known as acidifier, on the fibrillation and its disintegration of collagen was investigated. As collagen fibrillation is pH dependent, the pH modulation property of GdL is attractive to inhibit self-association of collagen. Optical density and microscopic data indicate that GdL elicits concentration-dependent fibril inhibition and also disintegrates pre-formed collagen fibrils. The simultaneous pH analysis showed that the modulation(lowering) of pH by GdL is the primary cause for its anti-fibrotic activity. The intact triple helical structure of collagen upon treatment of GdL suggests that collagen fibril disintegration can be achieved without affecting the native structure of collagen which is essential for any anti-fibrotic agents. Saturation transfer difference (STD) NMR result reveals that GdL is in proximity to collagen. The present results thus suggest that GdL provides a lead to design novel anti-fibrotic agents for the pathologies related to collagen deposition. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Total Testosterone Levels and the Effect of Sildenafil on Type 2 Diabetics with Erectile Dysfunction

    Directory of Open Access Journals (Sweden)

    Nabeel Najib Fadhil Hadeed

    2014-01-01

    Full Text Available Objectives: Hypotestosteronemia has been reported in approximately half of type 2 diabetic men in general. This study aims to assess serum total testosterone levels in type 2 diabetics with erectile dysfunction and to correlate the degree of improvement between sildenafil citrate and testosterone levels. Methods: A cross sectional and prospective comparative interventional study was conducted at the Diabetic Clinic of Assalam Teaching Hospital in Mosul, during the period from January 1, 2009 through to December 31, 2011. The study enrolled 120 type 2 diabetic males with erectile dysfunction who were analyzed with regard to age, duration of diabetes, duration and severity of erectile dysfunction, serum total testosteron levels and the degree of response to sildenafil citrate in terms of testosterone levels. The data were statistically analyzed using the independent two-sample Student t test, χ2 test and Pearson correlation test. A p-value of <0.05 was considered statistically significant. Results: Thirty six percent of type 2 diabetic males with erectile dysfunction were found to have low serum testosterone levels. The hypotestosteronemic and normotestosteronemic subgroups were not significantly different in terms of mean age, duration of diabetes, reduction of libido, and reduction in erectile function. The rate and the degree of improvement of erection by sildenafil in the normo-and-hypotestosteronemic respondents were not significantly different, but the degree of improvement by sildenafil was significantly correlated to testosterone levels among the hypotestosteronemic group. Conclusion: Hypotestosteronemia was found in 36% of type 2 diabetic males with erectile dysfunction. The degree of improvement of erectile dysfunction by sildenafil was directly proportional to the serum testosterone levels among the hypotestosteronemic group. Therapeutic supplement with testosterone preparation in the hypotestosteronemic diabetics with erectile

  7. Studies on sildenafil citrate (Viagra) interaction with DNA using electrochemical DNA biosensor.

    Science.gov (United States)

    Rauf, Sakandar; Nawaz, Haq; Akhtar, Kalsoom; Ghauri, Muhammad A; Khalid, Ahmad M

    2007-05-15

    The interaction of sildenafil citrate (Viagra) with DNA was studied by using an electrochemical DNA biosensor. The binding mechanism of sildenafil citrate was elucidated by using constant current potentiometry and differential pulse voltammetry at DNA-modified glassy carbon electrode. The decrease in the guanine oxidation peak area or peak current was used as an indicator for the interaction in 0.2M acetate buffer (pH 5). The binding constant (K) values obtained were 2.01+/-0.05 x 10(5) and 1.97+/-0.01 x 10(5)M(-1) with constant current potentiometry and differential pulse voltammetry, respectively. A linear dependence of the guanine peak area or peak current was observed within the range of 1-40 microM sildenafil citrate with slope=-2.74 x 10(-4)s/microM, r=0.989 and slope=-2.78 x 10(-3)microA/microM, r=0.995 by using constant current potentiometry and differential pulse voltammetry, respectively. Additionally, binding constant values for sildenafil citrate-DNA interaction were determined for the pH range of 4-8 and in biological fluids (serum and urine) at pH 5. The influence of sodium and calcium ions was also studied to elucidate the mechanism of sildenafil citrate-DNA interaction under different solution conditions. The present study may prove to be helpful in extending our understanding of the anticancer activity of sildenafil citrate from cellular to DNA level.

  8. Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

    Directory of Open Access Journals (Sweden)

    Mulhall JP

    2013-11-01

    Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

  9. Disintegration of monetary system of medieval Serbia

    Directory of Open Access Journals (Sweden)

    Gnjatović Dragana

    2014-01-01

    Full Text Available The subject matter of this paper is the process of gradual disintegration of monetary system of medieval Serbia during the second half of the 14th and the first half of the 15th century. This period is characterized by an appearance of frequent usurpations of the ruling right to mint coinage by local landlords and the attempts of the rulers from Lazarević and Branković families to restore unified monetary system. Common debasements and restorations of silver coinage provoked economic instability and induced frequent turning backwards to the custom of using weighted silver instead of silver coins as commodity monetary standard. The aim of this paper is to explain the reasons for those phenomena. We apply qualitative, historical, empirical analysis where we consider money minting right holders and their decisions to debase and restore the value of silver dinars. We found that gradual disintegration of monetary system of medieval Serbian State continued until the fall of Serbian Despotate as a consequence of political instability following dissolution of medieval Serbian Empire and economic and financial exhaustion of Serbia by Ottoman suzerains.

  10. Capsule shell material impacts the in vitro disintegration and dissolution behaviour of a green tea extract☆

    Science.gov (United States)

    Glube, Natalie; Moos, Lea von; Duchateau, Guus

    2013-01-01

    Purpose In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release. Methods A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times were determined together with the dissolution profiles in compendial and biorelevant media. Results All formulations disintegrated within 30 min, meeting the USP criteria for botanical formulations. An immediate release dissolution profile was achieved for gelatin capsules in all media but not for the specified HPMC formulations. Dissolution release was especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in FeSSIF media suggesting the potential for food interactions. Conclusions The delayed release from studied HPMC capsule materials is likely attributed to an interaction between the catechins, the major constituents of the green tea extract, and the capsule shell material. An assessment of in vitro dissolution is recommended prior to the release of a dietary supplement or clinical trial investigational product to ensure efficacy. PMID:25755998

  11. Capsule shell material impacts the in vitro disintegration and dissolution behaviour of a green tea extract.

    Science.gov (United States)

    Glube, Natalie; Moos, Lea von; Duchateau, Guus

    2013-01-01

    In vitro disintegration and dissolution are routine methods used to assess the performance and quality of oral dosage forms. The purpose of the current work was to determine the potential for interaction between capsule shell material and a green tea extract and the impact it can have on the release. A green tea extract was formulated into simple powder-in-capsule formulations of which the capsule shell material was either of gelatin or HPMC origin. The disintegration times were determined together with the dissolution profiles in compendial and biorelevant media. All formulations disintegrated within 30 min, meeting the USP criteria for botanical formulations. An immediate release dissolution profile was achieved for gelatin capsules in all media but not for the specified HPMC formulations. Dissolution release was especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in FeSSIF media suggesting the potential for food interactions. The delayed release from studied HPMC capsule materials is likely attributed to an interaction between the catechins, the major constituents of the green tea extract, and the capsule shell material. An assessment of in vitro dissolution is recommended prior to the release of a dietary supplement or clinical trial investigational product to ensure efficacy.

  12. Development of polymer-bound fast-dissolving metformin buccal film with disintegrants.

    Science.gov (United States)

    Haque, Shaikh Ershadul; Sheela, Angappan

    2015-01-01

    Fast-dissolving drug-delivery systems are considered advantageous over the existing conventional oral dosage forms like tablets, capsules, and syrups for being patient friendly. Buccal films are one such system responsible for systemic drug delivery at the desired site of action by avoiding hepatic first-pass metabolism. Metformin hydrochloride (Met), an antidiabetic drug, has poor bioavailability due to its high solubility and low permeability. The purpose of the study reported here was to develop a polymer-bound fast-dissolving buccal film of metformin to exploit these unique properties. In the study, metformin fast-dissolving films were prepared by the solvent-casting method using chitosan, a bioadhesive polymer. Further, starch, sodium starch glycolate, and microcrystalline cellulose were the disintegrants added to different ratios, forming various formulations (F1 to F7). The buccal films were evaluated for various parameters like weight variation, thickness, folding endurance, surface pH, content uniformity, tensile strength, and percentage of elongation. The films were also subjected to in vitro dissolution study, and the disintegration time was found to be less than 30 minutes for all formulations, which was attributed to the effect of disintegrants. Formulation F6 showed 92.2% drug release within 6 minutes due to the combined effect of sodium starch glycolate and microcrystalline cellulose.

  13. Development of polymer-bound fast-dissolving metformin buccal film with disintegrants

    Directory of Open Access Journals (Sweden)

    Haque SE

    2015-10-01

    Full Text Available Shaikh Ershadul Haque, Angappan Sheela Materials Chemistry Division, Centre for Nanomaterials, School of Advanced Sciences, VIT University, Vellore, India Abstract: Fast-dissolving drug-delivery systems are considered advantageous over the existing conventional oral dosage forms like tablets, capsules, and syrups for being patient friendly. Buccal films are one such system responsible for systemic drug delivery at the desired site of action by avoiding hepatic first-pass metabolism. Metformin hydrochloride (Met, an antidiabetic drug, has poor bioavailability due to its high solubility and low permeability. The purpose of the study reported here was to develop a polymer-bound fast-dissolving buccal film of metformin to exploit these unique properties. In the study, metformin fast-dissolving films were prepared by the solvent-casting method using chitosan, a bioadhesive polymer. Further, starch, sodium starch glycolate, and microcrystalline cellulose were the disintegrants added to different ratios, forming various formulations (F1 to F7. The buccal films were evaluated for various parameters like weight variation, thickness, folding endurance, surface pH, content uniformity, tensile strength, and percentage of elongation. The films were also subjected to in vitro dissolution study, and the disintegration time was found to be less than 30 minutes for all formulations, which was attributed to the effect of disintegrants. Formulation F6 showed 92.2% drug release within 6 minutes due to the combined effect of sodium starch glycolate and microcrystalline cellulose. Keywords: chitosan, sodium starch glycolate, microcrystalline cellulose, drug-delivery system, immediate release

  14. Sildenafil (Viagra Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

    Directory of Open Access Journals (Sweden)

    Catarina Raposo

    2013-01-01

    Full Text Available We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi, and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.

  15. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Directory of Open Access Journals (Sweden)

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  16. Disintegration of a profiled shock wave at the cumulation point

    International Nuclear Information System (INIS)

    Kaliski, S.

    1978-01-01

    The disintegration at the cumulation point is analyzed of a shock wave generated with the aid of a profiled pressure. The quantitative relations are analyzed for the disintegration waves for typical compression parameters in systems of thermonuclear microfusion. The quantitative conclusions are drawn for the application of simplifying approximate calculations in problems of microfusion. (author)

  17. Acoustics aspects of technological process in the rock disintegration

    Directory of Open Access Journals (Sweden)

    Jozef Futó

    2007-04-01

    Full Text Available The paper describes some results of monitoring and aspects of the acoustic signal in the rock disintegration on the drillig stand of the Institute of Geotechnics, SAS in Košice. The registration and processing of the acoustic signal is solved as a part of the research grant task within the basic research of the rock disintegration by drilling.

  18. Determination of disintegration half-life of 252Cf

    International Nuclear Information System (INIS)

    Chen Keliang; Liu Guoxing; Wang Sufang; Zheng Jiwen

    1991-01-01

    The follow-up measurements have been made by using a Si(Au) detector with small solid angle geometry for α disintegration of 252 Cf. The measured half-life of disintegration is 2.638 ± 0.009 year. This value is in accordance with other previous results

  19. Evaluation of binder and disintegrant properties of starch derived ...

    African Journals Online (AJOL)

    The aim of the study was to formulate metronidazole tablets using starch from Xanthosoma sagittifolium as binder and disintegrant in metronidazole tablets. Metronidazole tablets were produced by wet granulation method using X. sagittifolium starch as binder at concentrations of 5, 10, 15 and 20% w/w, and as disintegrant ...

  20. Effects Of Physical And Chemical Modifications On The Disintegrant ...

    African Journals Online (AJOL)

    Regardless of the mode of incorporation, Tacca starch was most efficient in effecting the disintegration of the tablets and releasing their riboflavin contents in its unmodified form. In this regard, pregelatinized Tacca starch was more effective as a disintegrant than the acid hydrolysed form of the starch. Generally, fastest ...

  1. Optimization of the formulation of fast disintegrating tablets

    NARCIS (Netherlands)

    Kamp, Herman Vincent van

    1987-01-01

    Chapter 1 presents general information on tableting and is an introduction to the other chapters. Chapter 2 covers the mechanism of action of tablet disintegrants, in particular modern super disintegrants. The results indicate that when the tablets contain a slightly swelling but hydrophilic

  2. Optimization of binder, disintegrant and compression pressure for ...

    African Journals Online (AJOL)

    This was done by studying the contributions of variable factors of binder concentration, disintegrant concentration and compression pressure to tablet friability, hardness and disintegration time under factor combinations given by 23 factorial experimental designs. The effect of every factor was determined by finding the ...

  3. A Review of Disintegration Mechanisms and Measurement Techniques.

    Science.gov (United States)

    Markl, Daniel; Zeitler, J Axel

    2017-05-01

    Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

  4. Mechanisms and kinetics models for ultrasonic waste activated sludge disintegration.

    Science.gov (United States)

    Wang, Fen; Wang, Yong; Ji, Min

    2005-08-31

    Ultrasonic energy can be applied as pre-treatment to disintegrate sludge flocs and disrupt bacterial cells' walls, and the hydrolysis can be improved, so that the rate of sludge digestion and methane production is improved. In this paper, by adding NaHCO3 to mask the oxidizing effect of OH, the mechanisms of disintegration are investigated. In addition, kinetics models for ultrasonic sludge disintegration are established by applying multi-variable linear regression method. It has been found that hydro-mechanical shear forces predominantly responsible for the disintegration, and the contribution of oxidizing effect of OH increases with the amount of the ultrasonic density and ultrasonic intensity. It has also been inferred from the kinetics model which dependent variable is SCOD+ that both sludge pH and sludge concentration significantly affect the disintegration.

  5. The Theory of Institutional Disintegration: Conceptual Potential and Methdological Frameworks

    Directory of Open Access Journals (Sweden)

    Barbashin Maksim, Y.

    2016-03-01

    Full Text Available The methodological opportunities and conceptual frameworks of theory of institutional disintegration developed by the author and the implication of the theory in market studies are analyzed. The problem of institutional transformation is one of the main theoretical problems in new institutionalism. The author believes that social institutions describe acceptable and unacceptable economic behavior for economic agents, and the institutional disintegration is the result of the gradual evolution of norms and rules of behavior. Institutional disintegration starts as the result of the growth of default rules. In the paper, institutional exceptions are considered to be a product of institutional disintegration and the behavioral foundations of new markets. The theory explains how “inner” transformation of rules of behavior impacts on market development and market behavior of economic agents. Analyzing the methodological advantages and problems of such approach, the author comes to the conclusions that the theory of institutional disintegration has some methodological perspectives in institutional economics and market studies.

  6. Effects of ultrasonic disintegration of excess sewage sludge.

    Science.gov (United States)

    Zielewicz, Ewa

    2016-10-01

    Breaking down sludge floc (sonodyspergation effect) and destruction of the cell membranes of microorganisms forming floc is a direct effect of ultrasonic disintegration of sludge excess. This results in release of organic material by liquid sludge (the sonolysis effect). Desired technological effects of the disintegration are: to shorten the hydrolytic phase of fermentation, to increase the production of biogas (source of renewable energy) and an increased mineralization (stability) of fermented sludge. The presented study demonstrates research covering thickened excess sludge of various physicochemical properties, collected from nine municipal sewage treatment plants. The sludge was subjected to ultrasonic disintegration using three differently constructed disintegrators and different proportions of sonification area. Direct effects of disintegration were monitored and recorded using selected indicators describing changes in the properties of sludge and increase of substance dispersed and dissolved in the supernatant liquid to be filtered. Studies have demonstrated that those (direct) effects of ultrasonic disintegration depend on the physicochemical properties of the sludge (foremost the concentration of dry solids) that determine their variable susceptibility to the disintegration methods. The direct effects also depend on optimal process conditions (which consist of the construction of the ultrasonic disintegrator), the geometric proportions of the sonication area and the operating parameters of disintegration (which could be appropriately matched to the characteristics of sludge). The most preferable results were obtained for ultrasonic disintegration of sludge with a dry matter concentration C 0 < 4.2 %. The highest effect of sonolysis-an almost 30-fold increase in the COD dissolved in the supernatant-was obtained for the sludge of lowest dry matter (C 0 = 2.0 %), which was sonicated in a reactor with a short transducer of the largest radiating surface

  7. A nanohybrid system for taste masking of sildenafil

    Directory of Open Access Journals (Sweden)

    Lee JH

    2012-03-01

    Full Text Available Ji-Hee Lee1,*, Goeun Choi1,*, Yeon-Ji Oh1, Je Won Park1, Young Bin Choy3, Mung Chul Park1, Yeo Joon Yoon1, Hwa Jeong Lee2, Hee Chul Chang4, Jin-Ho Choy1 1Center for Intelligent Nano-Bio Materials (CINBM, Department of Bioinspired Science and Department of Chemistry and Nano Science, 2Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Korea; 3Department of Biomedical Engineering, College of Medicine and Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul, Korea; 4Global Strategy Center and Pharmaceutical Research Institute, Daewoong Pharmaceutical Co., Ltd., Seoul, Korea*These authors contributed equally to this workAbstract: A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT, for taste masking of sildenafil (SDN. To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN–MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA. Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN–MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%, suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2 and compared the drug-release profiles of AEA-coated SDN–MMT and Viagra®, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN–MMT during the first 2 hours while almost 100% of drug was released from Viagra®. However, an in vivo experiment showed that the AEA-coated SDN–MMT exhibited higher drug exposure than Viagra®. For the AEA-coated SDN–MMT, the area under the plasma concentration–time curve from 0 hours to infinity (AUC0-∞ and maximum

  8. A nanohybrid system for taste masking of sildenafil

    Science.gov (United States)

    Lee, Ji-Hee; Choi, Goeun; Oh, Yeon-Ji; Park, Je Won; Choy, Young Bin; Park, Mung Chul; Yoon, Yeo Joon; Lee, Hwa Jeong; Chang, Hee Chul; Choy, Jin-Ho

    2012-01-01

    A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN–MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN–MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN–MMT and Viagra®, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN–MMT during the first 2 hours while almost 100% of drug was released from Viagra®. However, an in vivo experiment showed that the AEA-coated SDN–MMT exhibited higher drug exposure than Viagra®. For the AEA-coated SDN–MMT, the area under the plasma concentration– time curve from 0 hours to infinity (AUC0-∞) and maximum concentration (Cmax) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra® (AUC0-∞ = 69.2 ± 3.19 μg · hour/mL; Cmax = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure. PMID:22619517

  9. The effect of sildenafil citrate (Viagra) on visual sensitivity.

    Science.gov (United States)

    Stockman, Andrew; Sharpe, Lindsay T; Tufail, Adnan; Kell, Philip D; Ripamonti, Caterina; Jeffery, Glen

    2007-06-08

    The erectile dysfunction medicine sildenafil citrate (Viagra) inhibits phosphodiesterase type 6 (PDE6), an essential enzyme involved in the activation and modulation of the phototransduction cascade. Although Viagra might thus be expected to impair visual performance, reports of deficits following its ingestion have so far been largely inconclusive or anecdotal. Here, we adopt tests sensitive to the slowing of the visual response likely to result from the inhibition of PDE6. We measured temporal acuity (critical fusion frequency) and modulation sensitivity in four subjects before and after the ingestion of a 100-mg dose of Viagra under conditions chosen to isolate the responses of either their short-wavelength-sensitive (S-) cone photoreceptors or their long- and middle-wavelength-sensitive (L- and M-) cones. When vision was mediated by S-cones, all subjects exhibited some statistically significant losses in sensitivity, which varied from mild to moderate. The two individuals who showed the largest S-cone sensitivity losses also showed comparable losses when their vision was mediated by the L- and M-cones. Some of the losses appear to increase with frequency, which is broadly consistent with Viagra interfering with the ability of PDE6 to shorten the time over which the visual system integrates signals as the light level increases. However, others appear to represent a roughly frequency-independent attenuation of the visual signal, which might also be consistent with Viagra lengthening the integration time (because it has the effect of increasing the effectiveness of steady background lights), but such changes are also open to other interpretations. Even for the more affected observers, however, Viagra is unlikely to impair common visual tasks, except under conditions of reduced visibility when objects are already near visual threshold.

  10. Geochemical Fate and Transport of Sildenafil and Vardenafil

    Science.gov (United States)

    Richter, L.; Boudinot, G.; Vulava, V. M.; Cory, W. C.

    2015-12-01

    The geochemical fate of pharmaceuticals and their degradation products is a developing environmental field. The geologic, chemical, and biological fate of these pollutants has become very relevant with the increase in human population and the resulting increase in pollutant concentrations in the environment. In this study, we focus on sildenafil (SDF) and vardenafil (VDF), active compounds in Viagra and Levitra, respectively, two commonly used erectile dysfunction drugs. The main objective is to determine the sorption potential and transport behavior of these two compounds in natural soils. Both SDF and VDF are complex organic molecules with multiple amine functional groups in their structures. Two types of natural acidic soils (pH≈4.5), an organic-rich soil (7.6% OM) and clay-rich soil (5.1% clay) were used in this study to determine which soil components influence sorption behavior of both compounds. Sorption isotherms measured using batch reactors were nearly linear, but sorption was stronger in soil that contained higher clay content. Both compounds have multiple pKas due to the amine functional groups, the relevant pKas of SDF are 5.97 and 7.27, and those of VDF's are 4.72 and 6.21. These values indicate that these compounds likely behave as cations in soil suspensions and hence were strongly sorbed to negatively-charged clay minerals present in both soils. The clay composition in both soils is predominantly kaolinite with smaller amount of montmorillonite, both of which have a predominantly negative surface charge. Transport experiments using glass chromatography columns indicated that both compounds were more strongly retarded in the clay-rich soils. Breakthrough curves from the transport experiments were modeled using convection-dispersion transport equations. The organic matter in the soil seemed to play a less dominant role in the geochemistry in this study, but is likely to transform both compounds into derivative compounds as seen in other studies.

  11. Sildenafil reduces polyuria in rats with lithium-induced NDI.

    Science.gov (United States)

    Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

    2012-01-01

    Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

  12. Intravaginal Administration of Sildenafil Citrate Increases Blood Flow in the Bovine Uterus

    Directory of Open Access Journals (Sweden)

    Dzięcioł Michał

    2015-04-01

    Full Text Available The aim of the study was to evaluate the influence of sildenafil citrate administrated intravaginaly on the blood flow in the bovine uterus during dioestrus. Uterine blood flow was examined in six healthy adult cows. Sildenafil was administrated intravaginaly to each co w between the 6th and 8th d of the ovarian cycle, in the form of vaginal suppositories containing 100 mg of active substance at a dose of 100, 200, or 300 mg per animal. Uterine perfusion was estimated by the colour Doppler examination, and obtained results were analysed with the Pixel Flux Software (Chameleon, Germany. Moreover, cardiovascular parameters were also evaluated. Animals were examined before and five times after drug application (two times at 15 min intervals, and three times at 2 h intervals. A placebo suppository was also given to the cows. The analysis of the intensity and velocity of blood flow in the uterus proved that sildenafil administrated intravaginaly significantly increased blood flow in the uterus and the effect of increased perfusion was observed for 4 h and 30 min after administration. The effect of increased uterine perfusion was observed after low as well as high doses of sildenafil. Significant changes in the cardio-vascular parameters were not detected. There were no changes in the uterine perfusion as well as in cardiovascular parameters after placebo administration.

  13. Beliefs and social norms about sildenafil citrate (Viagra) misuse and perceived consequences among Houstonian teenage males.

    Science.gov (United States)

    Peters, Ronald J; Johnson, Regina J; Kelder, Steve; Meshack, Angela F; Jefferson, Troy

    2007-09-01

    In the current study, a qualitative approach was used to investigate relevant beliefs and norms associated with sildenafil citrate (Viagra) consumption, initiation, and perceived consequences. Focus groups were conducted with 43 young men aged 18 and 19 years who identified themselves as lifetime sildenafil citrate users. The majority of focus group participants believed that "curiosity" and "peer pressure" contributed to their initial use. Most revealed that they first heard about sildenafil citrate from television advertisements, family members, friends, or sporting events, and they were able to obtain the drug from their friends and family members or they stole it from their father or grandfather. These findings may highlight the relative importance of exposure to prescription drug messages among those to whom the message is not specifically targeted, that is, young men. It is possible that the sildenafil citrate television messages are recalled by not only older male audiences but also by teenagers and younger men, producing similar cognitive processing and curiosity in both age cohorts.

  14. Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

    Science.gov (United States)

    Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

    2009-03-01

    To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

  15. Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

    DEFF Research Database (Denmark)

    Clemmesen, Jens-Otto; Giraldi, Annamaria; Ott, Peter

    2008-01-01

    AIM: To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient (HVPG) in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver...

  16. Pulmonary hypertension in end-stage pulmonary sarcoidosis: therapeutic effect of sildenafil?

    DEFF Research Database (Denmark)

    Milman, N.; Burton, C.M.; Iversen, M.

    2008-01-01

    BACKGROUND: The objectives of this study were to assess the frequency and severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in patients with recalcitrant pulmonary sarcoidosis. METHODS: This investigation was a single-center, retrospective study of all patients (n = 25...

  17. ELECTRONIC ANALOG COMPUTER FOR DETERMINING RADIOACTIVE DISINTEGRATION

    Science.gov (United States)

    Robinson, H.P.

    1959-07-14

    A computer is presented for determining growth and decay curves for elements in a radioactive disintegration series wherein one unstable element decays to form a second unstable element or isotope, which in turn forms a third element, etc. The growth and decay curves of radioactive elements are simulated by the charge and discharge curves of a resistance-capacitance network. Several such networks having readily adjustable values are connected in series with an amplifier between each successive pair. The time constant of each of the various networks is set proportional to the half-life of a corresponding element in the series represented and the charge and discharge curves of each of the networks simulates the element growth and decay curve.

  18. Dynamical evolution and disintegration of comets

    Science.gov (United States)

    Kresak, L.

    Current concepts of the origin and evolution of comets are reviewed. The place of their formation from which they have been delivered into the Oort reservoir is still an open problem, but the region of the outermost planets appears most probable. The interplay of stellar and planetary perturbations can be traced by model computations which reveal both the general trends and the variety of individual evolutionary paths. The present structure of the system of comets is controlled by the dynamical evolution of its individual members, limited by their physical aging by disintegration. Where the lifetimes are short, as in the Jupiter family of short-period comets, an equilibrium between elimination and replenishment is established. The role of different destructive processes and the resulting survival times are discussed.

  19. Dynamical evolution and disintegration of comets

    International Nuclear Information System (INIS)

    Kresak, L.

    1982-01-01

    Current concepts of the origin and evolution of comets are reviewed. The place of their formation from which they have been delivered into the Oort reservoir is still an open problem, but the region of the outermost planets appears most probable. The interplay of stellar and planetary perturbations can be traced by model computations which reveal both the general trends and the variety of individual evolutionary paths. The present structure of the system of comets is controlled by the dynamical evolution of its individual members limited by their physical aging by disintegration. Where the lifetimes are short, as in the Jupiter family of short-period comets, an equilibrium between elimination and replenishment is established. The role of different destructive processes and the resulting survival times are discussed. (Auth.)

  20. Copper alloys disintegration using pulsating water jet

    Czech Academy of Sciences Publication Activity Database

    Lehocká, D.; Klich, Jiří; Foldyna, Josef; Hloch, Sergej; Królczyk, J. B.; Cárach, J.; Krolczyk, G.

    2016-01-01

    Roč. 82, March 2016 (2016), s. 375-383 ISSN 0263-2241 R&D Projects: GA MŠk(CZ) LO1406; GA MŠk ED2.1.00/03.0082 Institutional support: RVO:68145535 Keywords : pulsating water jet * generation of pulses * disintegration * surface morphology * copper alloys Subject RIV: JQ - Machines ; Tools Impact factor: 2.359, year: 2016 http://ac.els-cdn.com/S0263224116000154/1-s2.0-S0263224116000154-main.pdf?_tid=8f8d1de6-99e9-11e6-afbc-00000aacb362&acdnat=1477314089_59912e52847e91e2030d6a1afd09e7b2

  1. Determination of Ga-67 disintegration rate

    International Nuclear Information System (INIS)

    Fonseca, Katia A.; Koskinas, Maria F.; Dias, Mauro S.

    1996-01-01

    One of the consequences of the production by IPEN of new radioisotopes used in nuclear medicine, as the case of Ga-67, is the need of new standard sources of the radionuclide obtained in a fast and simple way. The Laboratorio de Metrologia de Radionuclideos at IPEN has a well-type ionization chamber system, the most suitable for this purpose. In order to calibrate this system it was necessary to standardize Ga-67 solutions by an absolute system. The present work gives details on the Ga-67 disintegration rate determination by an 4 π β-γ coincidence system, gamma spectrometry using an HPGe detector and measurements using a 1383A - type ionization chamber, in order to check the consistency in the adopted methodology. (author)

  2. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  3. Measurement of Choroidal Perfusion and Thickness Following Systemic Sildenafil (Viagra®)

    Science.gov (United States)

    Kim, David Y.; Silverman, Ronald H.; Chan, R.V. Paul; Khanifar, Aziz A.; Rondeau, Mark; Lloyd, Harriet; Schlegel, Peter; Coleman, D. Jackson

    2011-01-01

    Objective To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (ViagraR) using enhanced depth imaging spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high frequency digital ultrasound. Methods Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and two hours after ingesting 50 mg of sildenafil. Swept-scan high frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyze differences in choroidal flow and thickness at baseline and two hours after ingestion of sildenafil. Results Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47 to 7.80 times baseline (p=0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea, and 10.7% underneath the fovea (p<0.001 for all values). Conclusions Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms, and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow. PMID:22974308

  4. Sildenafil (Viagra for male erectile dysfunction: a meta-analysis of clinical trial reports

    Directory of Open Access Journals (Sweden)

    McQuay HJ

    2002-05-01

    Full Text Available Abstract Background Evaluation of company clinical trial reports could provide information for meta-analysis at the commercial introduction of a new technology. Methods Clinical trial reports of sildenafil for erectile dysfunction from September 1997 were used for meta-analysis of randomised trials (at least four weeks duration and using fixed or dose optimisation regimens. The main outcome sought was an erection, sufficiently rigid for penetration, followed by successful intercourse, and conducted at home. Results Ten randomised controlled trials fulfilled the inclusion criteria (2123 men given sildenafil and 1131 placebo. NNT or NNH were calculated for important efficacy, adverse event and discontinuation outcomes. Dose optimisation led to at least 60% of attempts at sexual intercourse being successful in 49% of men, compared with 11% with placebo; the NNT was 2.7 (95% confidence interval 2.3 to 3.3. For global improvement in erections the NNT was 1.7 (1.6 to 1.9. Treatment-related adverse events occurred in 30% of men on dose optimised sildenafil compared with 11% on placebo; the NNH was 5.4 (4.3 to 7.3. All cause discontinuations were less frequent with sildenafil (10% than with placebo (20%. Sildenafil dose optimisation gave efficacy equivalent to the highest fixed doses, and adverse events equivalent to the lowest fixed doses. Conclusion This review of clinical trial reports available at the time of licensing agreed with later reviews that had many more trials and patients. Making reports submitted for marketing approval available publicly would provide better information when it was most needed, and would improve evidence-based introduction of new technologies.

  5. Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Ivan Novitzky

    2016-01-01

    Full Text Available To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7 received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16, total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19 were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h bevacizumab injected mice (n=7 they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16 they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03 and sildenafil-treated (p=0.003 groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.

  6. Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Percival, Justin M; Whitehead, Nicholas P; Adams, Marvin E; Adamo, Candace M; Beavo, Joseph A; Froehner, Stanley C

    2012-09-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy caused by mutations in the dystrophin gene. Loss of dystrophin initiates a progressive decline in skeletal muscle integrity and contractile capacity which weakens respiratory muscles including the diaphragm, culminating in respiratory failure, the leading cause of morbidity and mortality in DMD patients. At present, corticosteroid treatment is the primary pharmacological intervention in DMD, but has limited efficacy and adverse side effects. Thus, there is an urgent need for new safe, cost-effective, and rapidly implementable treatments that slow disease progression. One promising new approach is the amplification of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signalling pathways with phosphodiesterase 5 (PDE5) inhibitors. PDE5 inhibitors serve to amplify NO signalling that is attenuated in many neuromuscular diseases including DMD. We report here that a 14-week treatment of the mdx mouse model of DMD with the PDE5 inhibitor sildenafil (Viagra(®), Revatio(®)) significantly reduced mdx diaphragm muscle weakness without impacting fatigue resistance. In addition to enhancing respiratory muscle contractility, sildenafil also promoted normal extracellular matrix organization. PDE5 inhibition slowed the establishment of mdx diaphragm fibrosis and reduced matrix metalloproteinase-13 (MMP-13) expression. Sildenafil also normalized the expression of the pro-fibrotic (and pro-inflammatory) cytokine tumour necrosis factor α (TNFα). Sildenafil-treated mdx diaphragms accumulated significantly less Evans Blue tracer dye than untreated controls, which is also indicative of improved diaphragm muscle health. We conclude that sildenafil-mediated PDE5 inhibition significantly reduces diaphragm respiratory muscle dysfunction and pathology in the mdx mouse model of Duchenne muscular dystrophy. This study provides new insights into the therapeutic utility of targeting defects in NO

  7. Analysis of electrochemical disintegration process of graphite matrix

    International Nuclear Information System (INIS)

    Tian Lifang; Wen Mingfen; Chen Jing

    2010-01-01

    The electrochemical method with ammonium nitrate as electrolyte was studied to disintegrate the graphite matrix from the simulative fuel elements for high temperature gas-cooled reactor. The influences of process parameters, including salt concentration, system temperature and current density, on the disintegration rate of graphite fragments were investigated in the present work. The experimental results showed that the disintegration rate depended slightly on the temperature and salt concentration. The current density strongly affected the disintegration rate of graphite fragments. Furthermore, the content of introduced oxygen in final graphite fragments was independent of the current density and the concentration of electrolyte. Moreover, the structural evolution of graphite was analyzed based on the microstructural parameters determined by X-ray diffraction profile fitting analysis using MAUD (material analysis using diffraction) before and after the disintegration process. It may safely be concluded that the graphite disintegration can be ascribed to the influences of the intercalation of foreign molecules in between crystal planes and the partial oxidation involved. The disintegration process was described deeply composed of intercalate part and further oxidation part of carbon which effected together to lead to the collapse of graphite crystals.

  8. Enhancement of ultrasonic disintegration of sewage sludge by aeration.

    Science.gov (United States)

    Zhao, He; Zhang, Panyue; Zhang, Guangming; Cheng, Rong

    2016-04-01

    Sonication is an effective way for sludge disintegration, which can significantly improve the efficiency of anaerobic digestion to reduce and recycle use of sludge. But high energy consumption limits the wide application of sonication. In order to improve ultrasonic sludge disintegration efficiency and reduce energy consumption, aeration was introduced. Results showed that sludge disintegration efficiency was improved significantly by combining aeration with ultrasound. The aeration flow rate, gas bubble size, ultrasonic density and aeration timing had impacts on sludge disintegration efficiency. Aeration that used in later stage of ultrasonic irradiation with low aeration flow rate, small gas bubbles significantly improved ultrasonic disintegration sludge efficiency. At the optimal conditions of 0.4 W/mL ultrasonic irradiation density, 30 mL/min of aeration flow rate, 5 min of aeration in later stage and small gas bubbles, ultrasonic sludge disintegration efficiency was increased by 45% and one third of ultrasonic energy was saved. This approach will greatly benefit the application of ultrasonic sludge disintegration and strongly promote the treatment and recycle of wastewater sludge. Copyright © 2015. Published by Elsevier B.V.

  9. The efficacy and safety of on-demand Elonza; a generic product of sildenafil in Thai men with erectile dysfunction.

    Science.gov (United States)

    Wijitsettakul, Udomsak; Pempongkosol, Sompol

    2013-06-01

    To evaluate the efficacy and safety of Elonza (generic product of sildenafil) 100 mg, a phosphodiesterase type 5 (PDE5) inhibitor, in Thai men with erectile dysfunction (ED). This prospective, Cohort study was conducted for eight weeks. Two hundred ten male patients, older than 20 years of age with ED were enrolled to receive generic product of sildenafil 100 mg taken as needed. Efficacy is evaluated through the International Index of Erectile Function (IIEF) scores for the five separate response domains, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction domain. After sildenafil administration, erectile function domain scores were significantly increased from baseline, 5.02 (p product of sildenafil, was an effective and well-tolerated treatment for ED in Thai men.

  10. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  11. Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis.

    Science.gov (United States)

    Musicki, Biljana; Bivalacqua, Trinity J; Champion, Hunter C; Burnett, Arthur L

    2014-02-01

    Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Continuous treatment with sildenafil reversed (P penis. Sildenafil treatment of WT mice did not affect any of these parameters. Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. © 2013 International Society for Sexual Medicine.

  12. Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

    Science.gov (United States)

    Fayed, Abdel-Hasseb A; Gad, Shereen B

    2011-12-01

    As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  13. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

    Directory of Open Access Journals (Sweden)

    Boersma Hester

    2009-04-01

    Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

  14. Effect of sildenafil (Viagra® on the genital reflexes of paradoxical sleep-deprived male rats

    Directory of Open Access Journals (Sweden)

    M.L. Andersen

    2007-11-01

    Full Text Available Since there is evidence that paradoxical sleep deprivation (PSD elicits penile erection (PE and ejaculation (EJ, and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group. The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL than in controls (365 ± 38 ng/dL, whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

  15. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects

    DEFF Research Database (Denmark)

    Kruuse, Christina; Thomsen, Lars Lykke; Jacobsen, Torsten Bjørn

    2002-01-01

    Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics...... of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms....

  16. Synthesis of core-shell magnetic molecularly imprinted polymers and detection of sildenafil and vardenafil in herbal dietary supplements

    International Nuclear Information System (INIS)

    Ding Meijuan; Wu Xiaoli; Yuan Lihua; Wang Shu; Li Yun; Wang Ruoyu; Wen Tingting; Du Shuhu; Zhou, Xuemin

    2011-01-01

    An analytical procedure for selective extraction of sildenafil and vardenafil in herbal dietary supplements (HDSs) has been set up by using the magnetic molecularly imprinted polymers (MMIPs) as the extraction and clean-up materials, followed by high performance liquid chromatography-ultraviolet (HPLC-UV). The MMIPs were prepared by a surface molecular imprinting technique, using Fe 3 O 4 magnetite as a magnetically susceptible component, sildenafil as template molecule, 2-(trifluoromethyl) acrylic acid (TFMAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as polymeric matrix components. The MMIPs were characterized by transmission electron microscope (TEM), Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM), respectively. The heterogeneity of the MMIPs was modeled with the Freundlich isotherm equation. The resulting MMIPs had high recognition ability and fast binding kinetics for sildenafil. The MMIPs were used as dispersive solid-phase extraction (DSPE) materials to selectively extract sildenafil and vardenafil from HDSs, the contents of sildenafil and vardenafil were found to be 8.05 and 3.86 μg g -1 , respectively, and the average recoveries in spiked HDSs were 70.91-91.75% with a relative standard deviation (R.S.D.) below 7%. The MMIPs were successfully used to selectively enrich and determine sildenafil and vardenafil from HDSs.

  17. Formulation and process considerations for the design of sildenafil-loaded polymeric microparticles by vibrational spray-drying

    DEFF Research Database (Denmark)

    Beck-Broichsitter, Moritz; Bohr, Adam; Aragão-Santiago, Leticia

    2017-01-01

    CONTEXT AND OBJECTIVE: The current study reports the preparation and characterization of sildenafil-loaded poly(lactide-co-glycolide) (PLGA)-based microparticles (MPs) by means of vibrational spray-drying. Emphasis was placed on relevant formulation and process parameters with influence on the pr......CONTEXT AND OBJECTIVE: The current study reports the preparation and characterization of sildenafil-loaded poly(lactide-co-glycolide) (PLGA)-based microparticles (MPs) by means of vibrational spray-drying. Emphasis was placed on relevant formulation and process parameters with influence......), respectively. Furthermore, interactions between sildenafil and the PLGA matrix were observed for the spray-dried MPs. Optimization of spray-drying conditions allowed for a fabrication of defined MPs (size range of ∼4-8 μm) displaying a high sildenafil encapsulation efficiency (>90%) and sustained sildenafil...... properties of the prepared powders. CONCLUSION: Identification of relevant formulation and spray-drying parameters enabled the fabrication of tailored sildenafil-loaded PLGA-based MPs, which meet the needs of the individual application (e.g. controlled drug delivery to the lungs)....

  18. Evaluation of disintegration and dissolution of chloroquine tablets in ...

    African Journals Online (AJOL)

    Evaluation of disintegration and dissolution of chloroquine tablets in some States in Northern Nigeria. ... This study seeks to assess the quality of chloroquine tablets in some States in Northern Nigeria by determining ... HOW TO USE AJOL.

  19. High energy disintegration of silver and bromine nuclei

    International Nuclear Information System (INIS)

    Goswami, K.; Goswami, T.D.

    1996-01-01

    A nucleus excited by high energy projectile, disintegrates by emitting particles and fragments. The multiplicity of charged particle and fragments cnn be determined from the tracks produced in detectors like nuclear emulsion

  20. Rheological properties of disintegrated sewage sludge

    Science.gov (United States)

    Wolski, Paweł

    2017-11-01

    The rheology of the sludge provides information about the capacity and the flow, which in the case of project tasks for the hydraulic conveying installation is an important control parameter. Accurate knowledge of the rheological properties of sludge requires the designation of rheological models. Models single and multiparameter (Ostwald, Bingham, Herschel-Bulkley'a, and others) allow an approximation of flow curves, and the determination of the boundaries of the flow of modified sludge allows you to control the process compaction or are dewatered sludge undergoing flow. The aim of the study was to determine the rheological parameters and rheological models of sludge conditioned by physical methods before and after the process of anaerobic digestion. So far, studies have shown that the application of conditioning in the preparation of sewage sludge increases shear stress, viscosity as well as the limits of flow in relation to the untreated sludge. Offset yield point by the application of a conditioning agent is associated with decreased flowability tested sludge, which has also been observed by analyzing the structure of the prepared samples. Lowering the yield point, and thus the shear stress was recorded as a result of the fermentation test of disintegrated sludge.

  1. Radiative corrections in neutrino-deuterium disintegration

    International Nuclear Information System (INIS)

    Kurylov, A.; Ramsey-Musolf, M.J.; Vogel, P.

    2002-01-01

    The radiative corrections of order α for the charged- and neutral-current neutrino-deuterium disintegration for energies relevant to the SNO experiment are evaluated. Particular attention is paid to the issue of the bremsstrahlung detection threshold. It is shown that the radiative corrections to the total cross section for the charged current reaction are independent of that threshold, as they must be for consistency, and amount to a slowly decreasing function of the neutrino energy E ν , varying from about 4% at low energies to 3% at the end of the 8 B spectrum. The differential cross section corrections, on the other hand, do depend on the bremsstrahlung detection threshold. Various choices of the threshold are discussed. It is shown that for a realistic choice of the threshold and for the actual electron energy threshold of the SNO detector, the deduced 8 B ν e flux should be decreased by about 2%. The radiative corrections to the neutral-current reaction are also evaluated

  2. The Theory of Institutional Disintegration: Conceptual Potential and Methdological Frameworks

    OpenAIRE

    Barbashin Maksim, Y.

    2016-01-01

    The methodological opportunities and conceptual frameworks of theory of institutional disintegration developed by the author and the implication of the theory in market studies are analyzed. The problem of institutional transformation is one of the main theoretical problems in new institutionalism. The author believes that social institutions describe acceptable and unacceptable economic behavior for economic agents, and the institutional disintegration is the result of the gradual evolution ...

  3. Development of natural gum based fast disintegrating tablets of glipizide

    OpenAIRE

    Antesh Kumar Jha; Dipak Chetia

    2012-01-01

    Dysphagia and risk of choking are leading causes of patient non-compliance in the self-administration of conventional tablets. To overcome these limitations of conventional tablets fast-disintegrating tablets were developed, using natural gums. Natural gums were evaluated for bulk swelling capacity. Powder mix containing natural gums and glipizide was evaluated for water sorption, swelling index and capillary action. For faster onset and immediate hypoglycemic action, the fast disintegrating ...

  4. Fragmentation of chromatin with 125I radioactive disintegrations

    International Nuclear Information System (INIS)

    Turner, G.N.; Nobis, P.; Dewey, W.C.

    1976-01-01

    The DNA in Chinese hamster cells was labeled first for 3 h with [ 3 H]TdR and then for 3 h with [ 125 I]UdR. Chromatin was extracted, frozen, and stored at -30 0 C until 1.0 x 10 17 and 1.25 x 10 17 disintegrations/g of labeled DNA occurred for 125 I and 3 H, respectively. Velocity sedimentation of chromatin (DNA with associated chromosomal proteins) in neutral sucrose gradients indicated that the localized energy from the 125 I disintegrations, which gave about 1 double-strand break/disintegration plus an additional 1.3 single strand breaks, selectively fragmented the [ 125 I] chromatin into pieces smaller than the [ 3 H] chromatin. In other words, 125 I disintegrations caused much more localized damage in the chromatin labeled with 125 I than in the chromatin labeled with 3 H, and fragments induced in DNA by 125 I disintegrations were not held together by the associated chromosomal proteins. Use of this 125 I technique for studying chromosomal proteins associated with different regions in the cellular DNA is discussed. For these studies, the number of disintegrations required for fragmenting DNA molecules of different sizes is illustrated

  5. INFLUENCE OF CARBOXYMETHYLCELLULOSE SODIUM AND LUTROL ON THE SWELLING INDEX AND DISINTEGRATION TIME OF BIOMUCOADHESIVE TABLETS WITH MICONAZOLE NITRATE.

    Science.gov (United States)

    Birsan, Magdalena; Scutariu, Monica Mihaela; Cojocaru, Ileana

    2016-01-01

    PURPOSE. To develop original pharmaceutical formulation with miconazole nitrate, biomucoadhesive tablets, used in antifungal medication. The oral biomucoadhesive tablets with miconazole nitrate were developed by direct compression of the excipient mixture: carboxymethylcellulose sodium and lutrol 6000, excipients used for bioadhesivity, mannitol as a sugar substitute and aerosil as a lubricant. The main goal of the study is to determine the disintegration time and the swelling index of biomucoadhesive tablets with miconazole nitrate in order to estimate the time of contact with mucosa, respectively the prolongation of drug substance release. The swelling index was calculated depending on time in all the 5 formulations that included the carboxymethylcellulose sodium and Lutrol 6000 as matrix-forming, and the studied were time and association ratio between polymers. Analysing the results, we noticed that out of the four excipients we used, carboxymethylcellulose sodium had the higher influence on the swelling index and disintegration time.

  6. Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.

    Science.gov (United States)

    Gupta, Abhay; Hunt, Robert L; Shah, Rakhi B; Sayeed, Vilayat A; Khan, Mansoor A

    2009-01-01

    The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

  7. Women taking the "blue pill" (sildenafil citrate): such a big deal?

    Science.gov (United States)

    Lo Monte, Giuseppe; Graziano, Angela; Piva, Isabella; Marci, Roberto

    2014-01-01

    For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra(®)) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option.

  8. Adsorption and inhibitive properties of sildenafil (Viagra) for zinc in hydrochloric acid solution

    Science.gov (United States)

    Fouda, A. S.; Ibrahim, H.; Atef, M.

    Sildenafil (Viagra) was investigated as corrosion inhibitor for Zn in 1 M HCl solution using chemical and electrochemical methods at 25 °C. Electrochemical results showed that this drug is efficient inhibitor for Zn in HCl and the inhibition efficiency (IE) reached to 91% at 300 ppm. The IE increases with the drug concentration and decreases with increasing temperature. The adsorption of this drug on Zn surface follows Langmuir adsorption isotherm. The polarization plots revealed that Sildenafil acts as a mixed-type inhibitor. The thermodynamic parameters of activation and adsorption were calculated and discussed. The surface morphology of the Zn specimens was evaluated using scanning electron microscope (SEM), energy dispersive X-ray (EDX), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) techniques.

  9. Women taking the “blue pill” (sildenafil citrate): such a big deal?

    Science.gov (United States)

    Lo Monte, Giuseppe; Graziano, Angela; Piva, Isabella; Marci, Roberto

    2014-01-01

    For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra®) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option. PMID:25422584

  10. Multifragment disintegrations of expanding nuclear systems

    International Nuclear Information System (INIS)

    Gelbke, K.

    1993-01-01

    Two phase transitions are expected to exist in bulk nuclear matter: a liquid-gas phase transition and a deconfinement transition to a quark-gluon plasma. In studies of nucleus-nucleus collisions, conditions similar to those pertaining to phase transitions in infinite systems can be created, but the fundamental problem yet to be solved is the identification of remnant signatures uniquely related to either of these phase transitions. Nuclear systems at densities and temperatures corresponding to the liquid-gas coexistence region can be produced in intermediate energy nucleus-nucleus collisions; they are expected to decay into many intermediate mass fragments (IMF's: Z=3-20). Recent investigations with low-threshold electronic 4π detector arrays have firmly established the occurrence of multifragment disintegrations of hot nuclear systems and allowed to challenge various theoretical approaches. In this talk, an overview of pertinent experimental results on multifragmentation will be presented and discussed. it will be shown that current microscopic transport theories designed to treat the growth of density fluctuations predict fragment multiplicities much smaller than observed experimentally. Measurements of the time scales of fragment formation are consistent with statistical model calculations for expanding hot nuclear system which indicate that fragments may form during a rather narrow time interval after the system has cooled and expanded to a density below that of normal nuclear matter. The expansion rate (and hence the fragment multiplicity) is sensitive to the equation of state (EOS). However, a number of recent results provide increasing evidence that current theoretical treatments need to be refined to allow an experimental determination of the EOS

  11. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  12. Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

    Science.gov (United States)

    Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

    2017-11-15

    Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

  13. New approaches to the synthesis of sildenafil analogues and their enzyme inhibitory activity

    Czech Academy of Sciences Publication Activity Database

    Mojzych, M.; Karczmarzyk, Z.; Wysocki, W.; Ceruso, M.; Supuran, C.T.; Kryštof, Vladimír; Urbanczyk-Lipkowska, Z.; Kalicki, P.

    2015-01-01

    Roč. 23, č. 7 (2015), s. 1421-1429 ISSN 0968-0896 R&D Projects: GA ČR GAP305/12/0783 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional support: RVO:61389030 Keywords : Sildenafil analogues * Pyrazolo[4,3-e][1,2,4] triazine * Sulfonamides Subject RIV: CE - Biochemistry Impact factor: 2.923, year: 2015

  14. Sildenafil Effect on Nitric Oxide Secretion by Normal Human Endometrial Epithelial Cells Cultured In vitro

    Directory of Open Access Journals (Sweden)

    Farzaneh Chobsaz

    2011-01-01

    Full Text Available Background: Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specificphosphodiesterase type 5. It increases intracellular nitric oxide (NO production in some cells.There are reports on its positive effect on uterine circulation, endometrial thickness, and infertilityimprovement. Endometrial epithelial cells (EEC play an important role in embryo attachment andimplantation. The present work investigates the effect of sildenafil on human EEC and their NOsecretion in vitro.Materials and Methods: In this experimental in vitro study, endometrial biopsies (n=10 werewashed in a phosphate buffered solution (PBS and digested with collagenase I (2 mg/ml in DMEM/F12 medium at 37°C for 90 minutes. Epithelial glands were collected by sequential filtrationthrough nylon meshes (70 and 40 μm pores, respectively. Epithelial glands were then treated withtrypsin to obtain individual cells. The cells were counted and divided into four groups: control and1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; themedia were changed every 3 days, and their supernatants were collected for the NO assay. NO wasmeasured by standard Greiss methods. Data were analyzed by one way ANOVA.Results: There was no significant difference between groups in cell count and NO secretion, but thelevel of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cellcount. EEC morphology changed into long spindle cells in the case groups.Conclusion: Sildenafil (1, 10, and 20 μM showed a mild proliferative effect on human EECnumbers, but no significant change was seen in NO production.

  15. Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt.

    Science.gov (United States)

    Sanphui, Palash; Tothadi, Srinu; Ganguly, Somnath; Desiraju, Gautam R

    2013-12-02

    Sildenafil is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Because of poor aqueous solubility of the drug, the citrate salt, with improved solubility and pharmacokinetics, has been marketed. However, the citrate salt requires an hour to reach its peak plasma concentration. Thus, to improve solubility and bioavailability characteristics, cocrystals and salts of the drug have been prepared by treating aliphatic dicarboxylic acids with sildenafil; the N-methylated piperazine of the drug molecule interacts with the carboxyl group of the acid to form a heterosynthon. Salts are formed with oxalic and fumaric acid; salt monoanions are formed with succinic and glutaric acid. Sildenafil forms cocrystals with longer chain dicarboxylic acids such as adipic, pimelic, suberic, and sebacic acids. Auxiliary stabilization via C-H···O interactions is also present in these cocrystals and salts. Solubility experiments of sildenafil cocrystal/salts were carried out in 0.1N HCl aqueous medium and compared with the solubility of the citrate salt. The glutarate salt and pimelic acid cocrystal dissolve faster than the citrate salt in a two hour dissolution experiment. The glutarate salt exhibits improved solubility (3.2-fold) compared to the citrate salt in water. Solubilities of the binary salts follow an inverse correlation with their melting points, while the solubilities of the cocrystals follow solubilities of the coformer. Pharmacokinetic studies on rats showed that the glutarate salt exhibits doubled plasma AUC values in a single dose within an hour compared to the citrate salt. The high solubility of glutaric acid, in part originating from the strained conformation of the molecule and its high permeability, may be the reason for higher plasma levels of the drug.

  16. Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

    Science.gov (United States)

    Nurnberg, H George; Hensley, Paula L; Gelenberg, Alan J; Fava, Maurizio; Lauriello, John; Paine, Susan

    2003-01-01

    Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (Psatisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

  17. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

    Directory of Open Access Journals (Sweden)

    Dinani Matoso Fialho de Oliveira Armstrong

    2013-04-01

    Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

  18. Characterization of sildenafil citrate tablets of different sources by near infrared chemical imaging and chemometric tools.

    Science.gov (United States)

    Sabin, Guilherme P; Lozano, Valeria A; Rocha, Werickson F C; Romão, Wanderson; Ortiz, Rafael S; Poppi, Ronei J

    2013-11-01

    The chemical imaging technique by near infrared spectroscopy was applied for characterization of formulations in tablets of sildenafil citrate of six different sources. Five formulations were provided by Brazilian Federal Police and correspond to several trademarks of prohibited marketing and one was an authentic sample of Viagra. In a first step of the study, multivariate curve resolution was properly chosen for the estimation of the distribution map of concentration of the active ingredient in tablets of different sources, where the chemical composition of all excipients constituents was not truly known. In such cases, it is very difficult to establish an appropriate calibration technique, so that only the information of sildenafil is considered independently of the excipients. This determination was possible only by reaching the second-order advantage, where the analyte quantification can be performed in the presence of unknown interferences. In a second step, the normalized histograms of images from active ingredient were grouped according to their similarities by hierarchical cluster analysis. Finally it was possible to recognize the patterns of distribution maps of concentration of sildenafil citrate, distinguishing the true formulation of Viagra. This concept can be used to improve the knowledge of industrial products and processes, as well as, for characterization of counterfeit drugs. Copyright © 2013. Published by Elsevier B.V.

  19. Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

    Science.gov (United States)

    Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

    2015-01-01

    The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

  20. Tablet disintegration studied by high-resolution real-time magnetic resonance imaging.

    Science.gov (United States)

    Quodbach, Julian; Moussavi, Amir; Tammer, Roland; Frahm, Jens; Kleinebudde, Peter

    2014-01-01

    The present work employs recent advances in high-resolution real-time magnetic resonance imaging (MRI) to investigate the disintegration process of tablets containing disintegrants. A temporal resolution of 75 ms and a spatial resolution of 80 × 80 µm with a section thickness of only 600 µm were achieved. The histograms of MRI videos were quantitatively analyzed with MATLAB. The mechanisms of action of six commercially available disintegrants, the influence of relative tablet density, and the impact of disintegrant concentration were examined. Crospovidone seems to be the only disintegrant acting by a shape memory effect, whereas the others mainly swell. A higher relative density of tablets containing croscarmellose sodium leads to a more even distribution of water within the tablet matrix but hardly impacts the disintegration kinetics. Increasing the polacrilin potassium disintegrant concentration leads to a quicker and more thorough disintegration process. Real-time MRI emerges as valuable tool to visualize and investigate the process of tablet disintegration.

  1. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-01-01

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

  2. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  3. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling.

    Science.gov (United States)

    Das, Anindita; Xi, Lei; Kukreja, Rakesh C

    2005-04-01

    We investigated the effect of sildenafil in protection against necrosis or apoptosis in cardiomyocytes. Adult mouse ventricular myocytes were treated with sildenafil (1 or 10 microM) for 1 h before 40 min of simulated ischemia (SI). Necrosis was determined by trypan blue exclusion and lactate dehydrogenase release following SI alone or plus 1 or 18 h of reoxygenation (RO). Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and mitochondrial membrane potential measured using a fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1). Sildenafil reduced necrosis as indicated by decrease in trypan blue-positive myocytes and leakage of lactate dehydrogenase compared with untreated cells after either SI or SI-RO. The number of terminal deoxynucleotidyl transferase-mediated nick end labeling-positive myocytes or loss of JC-1 fluorescence following SI and 18 h of RO was attenuated in the sildenafil-treated group with concomitant inhibition of caspase 3 activity. An early increase in Bcl-2 to Bax ratio with sildenafil treatment was also observed in myocytes after SI-RO. The increase of Bcl-2 expression by sildenafil was inhibited by nitric-oxide synthase (NOS) inhibitor, L-nitro-amino-methyl-ester. The drug also enhanced mRNA and protein content of inducible NOS (iNOS) and endothelial NOS (eNOS) in the myocytes. Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes. The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes. Reverse transcription-PCR, Western blots, and immunohistochemical assay confirmed the expression of phosphodiesterase-5 in mouse cardiomyocytes. These data provide strong evidence for a direct protective effect of sildenafil against necrosis and apoptosis through NO signaling pathway. The results may have possible

  4. Improvement of disintegrable properties of bone prosthetic phosphate cements

    International Nuclear Information System (INIS)

    Kaneda, Mitsumasa

    2007-01-01

    The author added a viscoelastic binder or bio-disintegrable polymer filler in αDT-cement (DTC) base, which consisting of α-tricalcium phosphate, tetracalcium phosphate and dicalcium phosphate anhydrous, in order to examine whether disintegrable properties of the bone prosthetic materials could be improved. The additive for the former binder was hydroxypropyl-cellulose and the latter filler, poly-(DL-lactide-co-glycolide) and they were mixed in various proportions with the base. At both sides of the cranial coronary suture of Japanese white rabbit, cavities (4 in total) were made at anteroposterior sites where those prosthetic cements were filled. At 1, 2 and 4 weeks later, the operated bone region was dissected out, its soft X-ray image was taken by the machine OMC603 (OHMICRON), and three-dimensional (3D) micro-focused XCT images, by Shimadzu SMX-130CT-SV. The trabecular thickness, bone volume and tissue volume ratio were calculated from the latter images by the trabecular structural measure software TRI/3Dbon (ROTAC). Disintegration rate of the cements was tested in water. Disintegrable properties were found to affect osteogenesis by giving the space for it, and thereby the choice of the ratio of the binder and disintegrable filler in the DTC makes it possible to design the most suitable cement needed. (R.T.)

  5. Disintegration of aerobic granules induced by trans-2-decenoic acid.

    Science.gov (United States)

    Cai, Pei-Jie; Xiao, Xiang; He, Yan-Rong; Li, Wen-Wei; Yu, Lei; Yu, Han-Qing

    2013-01-01

    One current major hurdle to practical implementation of aerobic granule technology is the frequent occurrence of granule disintegration during long-term operation. However, the mechanism behind this is largely unclear today. Here, 2-decenoic acid, which has been previously demonstrated to be released by Pseudomonas aeruginosa and disperse biofilms, was found to also induce the disintegration of aerobic granules. A comparison of the solution compositions from samples of only trans-2-decenoic acid, only aerobic granules, and granules added with trans-2-decenoic acid shows that bacteria and extracellular polymeric substances (EPS) were stripped from granule surface upon trans-2-decenoic acid dosing. Due to the possible toxicity of trans-2-decenoic acid at a saturation concentration, the disintegrated granules and the milky suspension in the disintegration test showed a significantly lower oxygen uptake rate than the un-integrated granules. This work suggests that trans-2-decenoic acid released by microbes might play a critical role in regulating the disintegration of aerobic granules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Numerical Simulation on Zonal Disintegration in Deep Surrounding Rock Mass

    Directory of Open Access Journals (Sweden)

    Xuguang Chen

    2014-01-01

    Full Text Available Zonal disintegration have been discovered in many underground tunnels with the increasing of embedded depth. The formation mechanism of such phenomenon is difficult to explain under the framework of traditional rock mechanics, and the fractured shape and forming conditions are unclear. The numerical simulation was carried out to research the generating condition and forming process of zonal disintegration. Via comparing the results with the geomechanical model test, the zonal disintegration phenomenon was confirmed and its mechanism is revealed. It is found to be the result of circular fracture which develops within surrounding rock mass under the high geostress. The fractured shape of zonal disintegration was determined, and the radii of the fractured zones were found to fulfill the relationship of geometric progression. The numerical results were in accordance with the model test findings. The mechanism of the zonal disintegration was revealed by theoretical analysis based on fracture mechanics. The fractured zones are reportedly circular and concentric to the cavern. Each fracture zone ruptured at the elastic-plastic boundary of the surrounding rocks and then coalesced into the circular form. The geometric progression ratio was found to be related to the mechanical parameters and the ground stress of the surrounding rocks.

  7. Numerical simulation on zonal disintegration in deep surrounding rock mass.

    Science.gov (United States)

    Chen, Xuguang; Wang, Yuan; Mei, Yu; Zhang, Xin

    2014-01-01

    Zonal disintegration have been discovered in many underground tunnels with the increasing of embedded depth. The formation mechanism of such phenomenon is difficult to explain under the framework of traditional rock mechanics, and the fractured shape and forming conditions are unclear. The numerical simulation was carried out to research the generating condition and forming process of zonal disintegration. Via comparing the results with the geomechanical model test, the zonal disintegration phenomenon was confirmed and its mechanism is revealed. It is found to be the result of circular fracture which develops within surrounding rock mass under the high geostress. The fractured shape of zonal disintegration was determined, and the radii of the fractured zones were found to fulfill the relationship of geometric progression. The numerical results were in accordance with the model test findings. The mechanism of the zonal disintegration was revealed by theoretical analysis based on fracture mechanics. The fractured zones are reportedly circular and concentric to the cavern. Each fracture zone ruptured at the elastic-plastic boundary of the surrounding rocks and then coalesced into the circular form. The geometric progression ratio was found to be related to the mechanical parameters and the ground stress of the surrounding rocks.

  8. Processing of tungsten scrap into powders by electroerosion disintegration

    International Nuclear Information System (INIS)

    Fominskii, L.P.; Leuchuk, M.V.; Myuller, A.S.; Tarabrina, V.P.

    1985-01-01

    Utilization of tungsten and tungsten alloy swarf and other waste and also of rejected and worn parts is a matter of great importance in view of the shortage of this metal. The authors examine the electroerosion (EE) disintegration of tungsten in water as a means of utilizing swarf and other loose waste. Unlike chemical methods, EE disintegration ensures ecological purity since there are no effluent waters or toxic discharges. Swarf and trimmings of rods of diameters up to 20 mm obtained after the lathe-turning of tungsten bars sintered from PVN and PVV tungsten powders were disintegrated in water at room temperature between tungsten electrodes. The phase composition of the powder was studied using FeK /SUB alpha/ radiation, by x-ray diffraction methods in a DRON-2 diffractometer with a graphite monochromator on the secondary beam. When tungsten is heated to boiling during EE disintegration, the impurities present in it can evaporate and burn out. Thus, tungsten powder produced by EE disintegration can be purer than the starting metal

  9. Influence of compression forces on tablets disintegration by AC Biosusceptometry.

    Science.gov (United States)

    Corá, Luciana A; Fonseca, Paulo R; Américo, Madileine F; Oliveira, Ricardo B; Baffa, Oswaldo; Miranda, José Ricardo A

    2008-05-01

    Analysis of physical phenomena that occurs during tablet disintegration has been studied by several experimental approaches; however none of them satisfactorily describe this process. The aim of this study was to investigate the influence of compression force on the tablets by associating the AC Biosusceptometry with consolidated methods in order to validate the biomagnetic technique as a tool for quality control in pharmaceutical processes. Tablets obtained at five compression levels were submitted to mechanical properties tests. For uncoated tablets, water uptake and disintegration force measurements were performed in order to compare with magnetic data. For coated tablets, magnetic measurements were carried out to establish a relationship between physical parameters of the disintegration process. According to the results, differences between the compression levels were found for water uptake, force development and magnetic area variation measurements. ACB method was able to estimate the disintegration properties as well as the kinetics of disintegration process for uncoated and coated tablets. This study provided a new approach for in vitro investigation and validated this biomagnetic technique as a tool for quality control for pharmaceutical industry. Moreover, using ACB will also be possible to test these parameters in humans allowing to establish an in vitro/in vivo correlation (IVIVC).

  10. Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet.

    Science.gov (United States)

    Veronin, Michael A; Nutan, Mohammad T; Dodla, Uday Krishna Reddy

    2014-10-01

    The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug products compared with the US innovator product are not

  11. Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Berger Ariel

    2012-12-01

    Full Text Available Abstract Background Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH impacts patterns of healthcare utilization and costs. Methods Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8 who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the “index date,” and claims data were compiled for all study subjects for 6 months prior to their index date (“pretreatment” and 6 months thereafter (“follow-up”; patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. Results A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD age was 52 (10 years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p  Conclusions The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

  12. Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer.

    Science.gov (United States)

    Greish, Khaled; Fateel, Maryam; Abdelghany, Sara; Rachel, Nanitha; Alimoradi, Houman; Bakhiet, Moiz; Alsaie, Ahmed

    2017-11-21

    Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of sildenafil on tumour vasculatures could result in an improvement of anticancer drug concentration in tumour tissues and hence improves its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro. Adding 1, 30 and 100 μM of Viagra to 1 μM of doxorubicin resulted in 1.8-fold, 6.2-fold and 21-fold statistically significant increases in its cytotoxic effect, respectively. As a result, 4T1 tumour-bearing mice showed up to 2.7-fold increase in drug concentrations of the fluorescent Dye DiI and doxorubicin in tumour tissues, as well as their nanoformulations. Animals treated with the combinations of both Sildenafil citrate and doxorubicin showed a statistically significant 4.7-fold reduction in tumour size compared to doxorubicin alone. This work highlights the effect of Sildenafil on tumour vasculatures and provides a rational for further testing the combination on breast cancer patients.

  13. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus.

    Science.gov (United States)

    Miller, Suzanne L; Loose, Jan M; Jenkin, Graham; Wallace, Euan M

    2009-01-01

    This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra; Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being. In fetal sheep, we induced IUGR at 105-110 days (0.7 gestation) using single umbilical artery ligation (SUAL). In SUAL and control animals, we measured uterine blood flow (UBF) and blood gases before and after sildenafil administration. SUAL fetuses were hypoxemic compared with controls. Following sildenafil, UBF was significantly decreased in both SUAL and control ewes for approximately 40 minutes. In response to sildenafil, pO(2) was decreased in SUAL and control fetuses and both groups displayed significant hypotension and tachycardia. At postmortem SUAL fetal body weight was significantly reduced by 23% compared with controls. Sildenafil does not improve UBF or fetal well being in SUAL-induced IUGR pregnancies and should be used with caution in IUGR and healthy pregnancies because of its detrimental effects on uteroplacental perfusion and on the fetus.

  14. Emotional changes in men treated with sildenafil citrate for erectile dysfunction: a double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Moncada, Ignacio; Martínez-Jabaloyas, José M; Rodriguez-Vela, Luis; Gutiérrez, Pedro R; Giuliano, Francois; Koskimaki, Juha; Farmer, Ian S; Renedo, Virginia Pascual; Schnetzler, Gabriel

    2009-12-01

    Erectile dysfunction (ED) has been associated with several comorbidities and can cause significant loss of quality of life and self-esteem. In men with ED, to use the validated Self-Esteem and Relationship (SEAR) questionnaire to evaluate changes in self-esteem associated with sildenafil treatment of ED and to assess changes dependent on concomitant comorbid conditions. This was a 14-week, international, randomized, parallel-group, double-blind, flexible-dose (25, 50, or 100 mg), placebo-controlled study of sildenafil in men aged >or=18 years with a clinical diagnosis of ED (score Erectile Function (IIEF) domain scores and in the intercourse success rate, and the response to the global efficacy assessment and to the global satisfaction assessment. A total of 841 patients were included in the intent-to-treat efficacy analysis (559 sildenafil, 282 placebo). Patients randomized to sildenafil had significantly greater change scores from baseline to the end of treatment on all components of the SEAR and all domains of the IIEF (P Erectile Function domain score (r = 0.6338, P emotional benefits of sildenafil in the treatment of ED were confirmed, overall and in men with comorbid hypertension, hyperlipidemia, benign prostatic hypertrophy, and/or depression. Using both the IIEF and the SEAR questionnaires provides a more complete assessment of ED.

  15. Positive Disintegration as a Process of Symmetry Breaking.

    Science.gov (United States)

    Laycraft, Krystyna

    2017-04-01

    This article presents an analysis of the positive disintegration as a process of symmetry breaking. Symmetry breaking plays a major role in self-organized patterns formation and correlates directly to increasing complexity and function specialization. According to Dabrowski, a creator of the Theory of Positive Disintegration, the change from lower to higher levels of human development requires a major restructuring of an individual's psychological makeup. Each level of human development is a relatively stable and coherent configuration of emotional-cognitive patterns called developmental dynamisms. Their main function is to restructure a mental structure by breaking the symmetry of a low level and bringing differentiation and then integration to higher levels. The positive disintegration is then the process of transitions from a lower level of high symmetry and low complexity to higher levels of low symmetry and high complexity of mental structure.

  16. Development and evaluation of mathematical model to predict disintegration time of fast disintegrating tablets using powder characteristics.

    Science.gov (United States)

    Goel, H; Arora, A; Tiwary, A K; Rana, V

    2011-02-01

    The objective of the study was to develop a mathematical model for predicting the disintegration time of fast disintegrating tablets (FDTs) by estimating the powder characteristics of powder blend prior to compression. A combination of chitosan-alginate complex and glycine in the ratio of 50:50 was used for preparing FDTs. The developed mathematical model allowed water sorption time (WST), effective pore radius (R(eff.p)) and swelling Index (SI) of powder mixture as well as tablet crushing strength to be successfully correlated with disintegration time (DT) of FDTs. The predicted model showed that disintegration time of FDTs to be directly correlated with powder characteristics and inversely correlated with tablet crushing strength. Furthermore, a correlation of 0.97 was obtained when DT of FDTs was compared with SI/(WST * R(eff.p)). This correlation was not affected by inclusion of water soluble (ondansetron hydrochloride or metaclopramide hydrochloride) or water insoluble (domperidone) drugs in the powder blend or FDTs. These observations indicated the versatility of the mathematical model in predicting the disintegration time of FDTs by evaluating the selected characteristics of the powder blends without actually preparing the FDTs.

  17. Centrality of collisions and total disintegration of nuclei

    International Nuclear Information System (INIS)

    Sulejmanov, M.K.; Abdinov, O.B.; Anoshin, A.I.; Bogdanowicz, J.; Kuznetsov, A.A.

    1998-01-01

    The interrelation of the processes of total disintegration of nuclei with the process, characterized by the 'centrality' of collisions and a minimum flow of energy of secondary particles emitted at a zero angle in pC, dC, 4 HeC and 12 CC interactions, is investigated at 4.2 A · GeV/c. The events with total disintegration of nuclei are characterized by a high degree 'centrality' of collisions and similar to the events having a minimum flow of energy of particles emitted at a zero angle

  18. EVIDENCE FOR GAS FROM A DISINTEGRATING EXTRASOLAR ASTEROID

    International Nuclear Information System (INIS)

    Xu, S.; Jura, M.; Zuckerman, B.; Dufour, P.

    2016-01-01

    We report high-resolution spectroscopic observations of WD 1145+017—a white dwarf that was recently found to be transitted by multiple asteroid-sized objects within its tidal radius. We discovered numerous circumstellar absorption lines with linewidths of ∼300 km s −1 from Mg, Ca, Ti, Cr, Mn, Fe, and Ni, possibly from several gas streams produced by collisions among the actively disintegrating objects. The atmosphere of WD 1145+017 is polluted with 11 heavy elements, including O, Mg, Al, Si, Ca, Ti, V:, Cr, Mn, Fe, and Ni. Evidently, we are witnessing the active disintegration and subsequent accretion of an extrasolar asteroid

  19. EVIDENCE FOR GAS FROM A DISINTEGRATING EXTRASOLAR ASTEROID

    Energy Technology Data Exchange (ETDEWEB)

    Xu, S. [European Southern Observatory, Karl-Schwarzschild-Straße 2, D-85748 Garching (Germany); Jura, M.; Zuckerman, B. [Department of Physics and Astronomy, University of California, Los Angeles CA 90095-1562 (United States); Dufour, P., E-mail: sxu@eso.org, E-mail: jura@astro.ucla.edu, E-mail: ben@astro.ucla.edu, E-mail: dufourpa@astro.umontreal.ca [Institut de Recherche sur les Exoplanètes (iREx), Université de Montréal, Montréal, QC H3C 3J7 (Canada)

    2016-01-10

    We report high-resolution spectroscopic observations of WD 1145+017—a white dwarf that was recently found to be transitted by multiple asteroid-sized objects within its tidal radius. We discovered numerous circumstellar absorption lines with linewidths of ∼300 km s{sup −1} from Mg, Ca, Ti, Cr, Mn, Fe, and Ni, possibly from several gas streams produced by collisions among the actively disintegrating objects. The atmosphere of WD 1145+017 is polluted with 11 heavy elements, including O, Mg, Al, Si, Ca, Ti, V:, Cr, Mn, Fe, and Ni. Evidently, we are witnessing the active disintegration and subsequent accretion of an extrasolar asteroid.

  20. On Coulomb disintegration of relativistic nuclei and hypernuclei

    International Nuclear Information System (INIS)

    Lyuboshits, V.L.

    1989-01-01

    The dependence of the total cross-section of excitation and disintegration of a relativistic nucleus in the Coulomb field on the energy and parameters characterizing nuclear dimensions is investigated. The analogy with the problem of atomic ionization at the passage of charged particles through matter is used. The results are applied to the description of the Coulomb dissociation of nuclei with small binding energies. An explicit expression for the effective cross-section of the Coulomb disintegration of the hypernucleus-Λ 3 H into a deuteron and Λ-particle. 12 refs

  1. Drug abuse: consequences in terms of family pathology and disintegration.

    Science.gov (United States)

    Visser, L

    1991-01-01

    This article examines some of the consequences of drug addiction in terms of family pathology and family disintegration. It briefly elucidates the role of the family in developing and maintaining drug addiction in family members. The concept of 'secondary' sufferers of the illness of drug addiction is examined. An actual case history will be presented in order to facilitate analysis of some of the forms of pathology and disintegration so often seen in the family of the drug addict. Within the family context, the question of who, if anyone, is the victim of drug addiction, is raised.

  2. Disintegration of C60 by Xe ion irradiation

    International Nuclear Information System (INIS)

    Kalish, R.; Samoiloff, A.; Hoffman, A.; Uzan-Saguy, C.

    1993-01-01

    The Changes in resistivity of fullerene (C 60 ) films subject to 320 keV Xe ion irradiation are investigated as a function of ion dose. From a comparison of this dependence with similar data on other Xe irradiated C containing insulating materials and with data on C implanted fused quartz, it is concluded that upon ion impact C 60 clusters completely disintegrate. This disintegration releases about 60 C atoms which disperse amongst the remaining intact C 60 spheres giving rise to hopping conductivity between isolated C atoms. 16 refs., 3 figs

  3. Sildenafil, a selective phosphodiesterase type 5 inhibitor, enhances memory reconsolidation of an inhibitory avoidance task in mice.

    Science.gov (United States)

    Boccia, M M; Blake, M G; Krawczyk, M C; Baratti, C M

    2011-07-07

    Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Examination of formulation and process factors on the characteristics of fast dissolving and fast disintegrating tablets manufactured by a direct compression process.

    OpenAIRE

    Pabari, Ritesh M

    2010-01-01

    Oral dosage forms are the safest and most convenient dosage forms and of these tablets are the most popular with patients because of their portability, ease and convenience of dose intake and with manufacturers because of their simple and low cost manufacturing process. Fast disintegrating dissolving tablets (FDDTs), a more recent innovation, have gained a great deal of attention particularly for use in various patient groups such as the paediatric, geriatric, travelling patients and patients...

  5. Use of sildenafil citrate in a cat with Eisenmenger’s syndrome and an atrial septal defect

    Directory of Open Access Journals (Sweden)

    Ke Shuan Chow

    2015-04-01

    Full Text Available A 2-year-old male neutered Siamese cat presenting with weakness and dyspnoea was diagnosed with an atrial septal defect and pulmonary hypertension, which resulted in right-to-left shunting (Eisenmenger’s syndrome. The cat was treated with sildenafil (0.25–0.6 mg/kg for 10 months. There were no apparent treatment-related adverse effects. Improvement in clinical signs was noted, although increasing doses of sildenafil were required. After 10 months the cat significantly deteriorated and was euthanased.

  6. Use of multiple pinhole external scintigraphy to monitor tablet disintegration in vivo

    International Nuclear Information System (INIS)

    Theodorakis, M.C.; Devous, M.D.; Simpson, D.R.

    1982-01-01

    External scintigraphy is useful for observing the disintegration of capsules and tablets in the gastro-intestinal tract of man and animals. The sites of disintegration, completeness of disintegration, effectiveness of coatings and rate of transition through the intestinal tract can be investigated by this technique. Gamma cameras are coupled to a digital data processor, video image processor and image magnifier, for increased resolution. Disintegration times in vitro and in vivo are compared. (U.K.)

  7. Description of disintegration in a three-body system

    CERN Document Server

    Takibaev, N Z

    2000-01-01

    In the frame of approach based on the effective potential of interaction between constituents, description of inelastic transition, in particularly, the processes of system disintegration. Relationship is shown between the approach results and those of the theory of final state interaction where coefficients of reaction gaining factor are determined. (author)

  8. Dabrowski's Theory of Positive Disintegration and Giftedness: Overexcitability Research Findings

    Science.gov (United States)

    Mendaglio, Sal; Tillier, William

    2006-01-01

    During the past 20 years, a significant body of literature has emerged focusing on the application of Dabrowski's theory of positive disintegration (TPD) to the study of gifted individuals. Although much of this literature is prescriptive, some research reports spanning this time period are available. A perusal of research on TPD's applicability…

  9. Chemokine Signaling during Midline Epithelial Seam Disintegration Facilitates Palatal Fusion

    Science.gov (United States)

    Suttorp, Christiaan M.; Cremers, Niels A.; van Rheden, René; Regan, Raymond F.; Helmich, Pia; van Kempen, Sven; Kuijpers-Jagtman, Anne M.; Wagener, Frank A.D.T.G.

    2017-01-01

    Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling. PMID:29164113

  10. Disintegration of fluids under supercritical conditions from mixing layer studies

    Science.gov (United States)

    Okong'o, N.; Bellan, J.

    2003-01-01

    Databases of transitional states obtained from Direct Numerical simulations (DNS) of temporal, supercritical mixing layers for two species systems, O2/H2 and C7H16/N2, are analyzed to elucidate species-specific turbulence aspects and features of fluid disintegration.

  11. Mechanism of 238U disintegration induced by relativistic particles

    International Nuclear Information System (INIS)

    Andronenko, L.N.; Zhdanov, A.A.; Kravtsov, A.V.; Solyakin, G.E.

    2002-01-01

    In heavy-nucleus disintegration induced by a relativistic projectile particle, the production of collinear massive fragments accompanied by numerous charged particles and neutrons is explained in terms of the mechanism of projectile-momentum compensation due to the emission of a particle whose mass is greater than the projectile mass

  12. Childhood disintegrative disorder misdiagnosed as childhood-onset ...

    African Journals Online (AJOL)

    Childhood disintegrative disorder (CDD) is a rare pervasive developmental disorder, which is often misdiagnosed as schizophrenia, probably due to the resultant severe social impairment and withdrawn behaviour with stereotypys that could be mistaken for psychosis. We report a case of CDD that was misdiagnosed by a ...

  13. Discrete convolution-operators and radioactive disintegration. [Numerical solution

    Energy Technology Data Exchange (ETDEWEB)

    Kalla, S L; VALENTINUZZI, M E [UNIVERSIDAD NACIONAL DE TUCUMAN (ARGENTINA). FACULTAD DE CIENCIAS EXACTAS Y TECNOLOGIA

    1975-08-01

    The basic concepts of discrete convolution and discrete convolution-operators are briefly described. Then, using the discrete convolution - operators, the differential equations associated with the process of radioactive disintegration are numerically solved. The importance of the method is emphasized to solve numerically, differential and integral equations.

  14. The Disintegration of {sup 103}Rh{sup m}

    Energy Technology Data Exchange (ETDEWEB)

    Czock, K. H.; Haselberger, N.; Reichel, F. [International Atomic Energy Agency, Vienna (Austria)

    1974-09-15

    A technique for determination of the disintegration rate of {sup 103}Rh{sup m} in thick foils is described. In addition values for the following parameters were determined: - total internal conversion coefficient {alpha} = 1531 {+-} 30; - K shell internal conversion coefficient {alpha}{sub K} = 127 {+-} 6; - conversion ratio R= K/L+M+..... = 0.0914 {+-} 0.0043. (author)

  15. Disintegrating perineal disease: A variant of watering-can perineum

    African Journals Online (AJOL)

    N. Abrol

    www.ees.elsevier.com/afju · www.sciencedirect.com. Case report. Disintegrating perineal disease: A variant of watering-can perineum. N. Abrol. ∗. , A. Devasia. Department of Urology, Christian Medical College, Vellore, India. Received 11 January 2014; received in revised form 11 January 2014; accepted 11 March 2014.

  16. The use of hydrodynamic disintegration as a means to improve ...

    African Journals Online (AJOL)

    2008-09-15

    Sep 15, 2008 ... The gradual break–up of the bacterial cell walls limits the degradation process. By applying hydrodynamic disintegration the lysis of cells occurs in minutes instead of days. The intracel- lular and extracellular components are set free and are imme- diately available for biological degradation which leads to ...

  17. Evaluation of binder and disintegrant properties of starch derived ...

    African Journals Online (AJOL)

    AMARA

    2013-05-15

    May 15, 2013 ... Full Length Research Paper. Evaluation of binder and disintegrant properties of starch derived from Xanthosoma sagittifolium in metronidazole tablets. Onyishi Ikechukwu V., Chime Salome A.* and Ugwu Jonathan C. Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, ...

  18. Chemokine Signaling during Midline Epithelial Seam Disintegration Facilitates Palatal Fusion

    Directory of Open Access Journals (Sweden)

    Christiaan M. Suttorp

    2017-10-01

    Full Text Available Disintegration of the midline epithelial seam (MES is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO, which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling.

  19. Interactions Of Binder, Disintegrant And Compression Pressure In ...

    African Journals Online (AJOL)

    Binders, disintegrants and compression pressures play important roles in producing good tablets. The interactions between these three factors were analyzed to observe how they contribute to tablet properties. The concentration levels of the factors were determined using 23 factorial study designs by wet granulation ...

  20. Evaluation of disintegrant properties of Neorautanenia mitis starch ...

    African Journals Online (AJOL)

    Tablet formulations containing NMS had similar hardness with those containing MS at 0.5 MT while hardness was observed to increase with increase in compression pressure. Tablets containing NMS were found to elicit faster tablet disintegration than those containing maize starch BP and also had higher t75 values.

  1. Performance of tablet disintegrants: impact of storage conditions and relative tablet density.

    Science.gov (United States)

    Quodbach, Julian; Kleinebudde, Peter

    2015-01-01

    Tablet disintegration can be influenced by several parameters, such as storage conditions, type and amount of disintegrant, and relative tablet density. Even though these parameters have been mentioned in the literature, the understanding of the disintegration process is limited. In this study, water uptake and force development of disintegrating tablets are analyzed, as they reveal underlying processes and interactions. Measurements were performed on dibasic calcium phosphate tablets containing seven different disintegrants stored at different relative humidities (5-97%), and on tablets containing disintegrants with different mechanisms of action (swelling and shape recovery), compressed to different relative densities. Disintegration times of tablets containing sodium starch glycolate are affected most by storage conditions, which is displayed in decreased water uptake and force development kinetics. Disintegration times of tablets with a swelling disintegrant are only marginally affected by relative tablet density, whereas the shape recovery disintegrant requires high relative densities for quick disintegration. The influence of relative tablet density on the kinetics of water uptake and force development greatly depends on the mechanism of action. Acquired data allows a detailed analysis of the influence of storage conditions and mechanisms of action on disintegration behavior.

  2. Sludge disintegration techniques - assessment of their impacts on solubilization of organic carbon and methane production

    OpenAIRE

    Fatoorehchi, Elham

    2016-01-01

    In the present thesis, ozone, sodium hydroxide and ultrasound were conducted to disintegrate the excess sludge prior to anaerobic digestion with the aim of improving methane production. The impacts of different sludge disintegration methods on the molecular size distribution of DOC solubilized after disintegration were investigated using size exclusion chromatography with online organic carbon detection (SEC-OCD).

  3. Parametrization of the cross sections for complete disintegration of nuclei at relativistic energies

    International Nuclear Information System (INIS)

    Bogdanov, V.G.; Plyushchev, V.A.; Solov'eva, Z.I.

    1988-01-01

    A phenomenological analysis of observations of the complete disintegration of target nuclei in emulsions in relativistic heavy-ion reactions is given. On the basis of the probability of complete disintegration obtained from the observations it is possible to determine the value of the disintegration cross sections. A parametrizatio of these inelastic cross sections is formulated

  4. AN INTEGRATED COMPUTER-AIDED APPROACH FOR MODELING DISINTEGRATION-RELATED PHENOMENA

    NARCIS (Netherlands)

    CARAMELLA, C.; FERRARI, F.; RONCHI, M.; Smilde, A. K.

    1990-01-01

    Two phenomena have frequently been related to tablet disintegration: water uptake and disintegrating force development. The combination of these two measures allowed a step forward to understanding disintegration mechanisms. In the present work, multiple linear regression analysis was used to relate

  5. Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.

    Science.gov (United States)

    Hsiao, H-L; Langenickel, T H; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, M F; Sunkara, G; Rajman, I

    2018-03-01

    Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, three-period, single sequence study, patients with mild-to-moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and C max of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (-5/-4/-4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  6. Evaluation of Pharmacokinetic and Pharmacodynamic Drug–Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild‐to‐Moderate Hypertension

    Science.gov (United States)

    Langenickel, TH; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, MF; Sunkara, G; Rajman, I

    2017-01-01

    Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open‐label, three‐period, single sequence study, patients with mild‐to‐moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and Cmax of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (–5/–4/–4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. PMID:28599060

  7. The protective effects of sildenafil in acute lung injury in a rat model of severe scald burn: A biochemical and histopathological study.

    Science.gov (United States)

    Gokakin, Ali Kagan; Deveci, Koksal; Kurt, Atilla; Karakus, Boran Cihat; Duger, Cevdet; Tuzcu, Mehmet; Topcu, Omer

    2013-09-01

    Severe burn induces biochemical mediators such as reactive oxygen species that leads to lipid peroxidation which may have a key role in formation of acute lung injury (ALI). Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil preserves alveolar growth, angiogenesis, reduces inflammation and airway reactivity. The purpose of the present study was to evaluate the effects of different dosages of sildenafil in ALI due to severe scald burn in rats. Twenty-four rats were subjected to 30% total body surface area severe scald injury and were randomly divided into three equal groups as follow: control, 10 and 20mg/kg sildenafil groups. Levels of malondialdehyde (MDA), activities of glutathione peroxidase (Gpx), catalase (Cat), total oxidative stress (TOS), and total antioxidative capacity (TAC) were measured in both tissues and serums. Oxidative stress index (OSI) was calculated. A semi-quantitative scoring system was used for the evaluation of histopatological findings. Sildenafil increased Gpx, Cat, TAC and decreased MDA, TOS and OSI. Sildenafil decreased inflammation scores in lungs. Our results reveal that sildenafil is protective against scald burn related ALI by decreasing oxidative stress and inflammation and the dosage of 10mg/kg could be apparently better than 20mg/kg. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  8. The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study.

    Science.gov (United States)

    Gökakın, Ali Kağan; Atabey, Mustafa; Deveci, Koksal; Sancakdar, Enver; Tuzcu, Mehmet; Duger, Cevdet; Topcu, Omer

    2014-09-01

    Severe burn induces systemic inflammation and reactive oxygen species leading to lipid peroxidation which may play role in remote organs injury. Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil reduces oxidative stress and inflammation in distant organs. The aim of the present study was to evaluate the effects of different dosages of sildenafil in remote organs injury. A total of thirty-two rats were randomly divided into four equal groups. The groups were designated as follows: Sham, Control, 10, and T20 mg/kg sildenafil treatment groups. Levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), VEGF receptor (Flt-1), activities of glutathione peroxidase (Gpx), levels of total antioxidative capacity (TAC), and total oxidant status (TOS) were measured in both tissues and serum, and a semi-quantitative scoring system was used for the evaluation of histopathological findings. Sildenafil increased levels of Gpx, and Flt-1, and decreased MDA and VEGF levels in tissues. Sildenafil also increased serum levels of TAC and Flt-1 and decreased TOS, OSI, and VEGF. Sildenafil decreased inflammation scores in remote organs in histopathological evaluation. It has protective effects in severe burn-related remote organ injuries by decreasing oxidative stress and inflammation.

  9. Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

    Directory of Open Access Journals (Sweden)

    Silvia Elaine Ferreira-Melo

    2011-01-01

    Full Text Available OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME. METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part by the inhibition of phosphodiesterase-5.

  10. Effect of sildenafil citrate on women affected by sexual dysfunction referred to health clinics

    Directory of Open Access Journals (Sweden)

    Sanaz Zeinalzadeh

    2017-06-01

    Full Text Available Background. Female sexual dysfunction is a serious, multifactorial problem which affects women’s quality of life. Objectives. This study aimed at assessing the effect of sildenafil citrate on sexual dysfunction among women of reproductive age. Materials and methods. The present randomized clinical trial was conducted on 84 married women between 18 and 40 years old who suffered from sexual dysfunction. The inclusion criteria of the study were being married and between 18–40 years old, obtaining scores ≥ 22 in FSFI, not having a history of hypothyroidism or hyperprolactinemia, and not suffering from dyspareunia or vaginismus. The intervention group was required to consume 50 mg sildenafil citrate 1 hour before sexual intercourse for 5 weeks, and the control group received placebo. FSFI was completed by both study groups before and 5 weeks after the treatment. The data were analyzed through SPSS (v. 18 and paired t-test and independent t-test. Results . Most of the women (67.2% were between 30 and 40 years old. The study results revealed a significant difference between the two groups regarding the mean scores of sexual desire (p = 0.011, sexual arousal (p = 0.001, lubrication (p = 0.026, orgasm and sexual satisfaction (p < 0.001, and the whole dimension (p < 0.001. Besides, total mean sexual function before and after for the intervention and control groups was 21.1 ± 3.28 vs. 17.22 ± 5.9 (p < 0.001. Conclusion . In this study, sildenafil citrate was effective in enhancing sexual desire, arousal, orgasm, and sexual satisfaction. Of course, more studies need to be conducted on this issue.

  11. Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics.

    Science.gov (United States)

    Kindgen, Sarah; Wachtel, Herbert; Abrahamsson, Bertil; Langguth, Peter

    2015-09-01

    Disintegration of oral solid dosage forms is a prerequisite for drug dissolution and absorption and is to a large extent dependent on the pressures and hydrodynamic conditions in the solution that the dosage form is exposed to. In this work, the hydrodynamics in the PhEur/USP disintegration tester were investigated using computational fluid dynamics (CFD). Particle image velocimetry was used to validate the CFD predictions. The CFD simulations were performed with different Newtonian and non-Newtonian fluids, representing fasted and fed states. The results indicate that the current design and operating conditions of the disintegration test device, given by the pharmacopoeias, are not reproducing the in vivo situation. This holds true for the hydrodynamics in the disintegration tester that generates Reynolds numbers dissimilar to the reported in vivo situation. Also, when using homogenized US FDA meal, representing the fed state, too high viscosities and relative pressures are generated. The forces acting on the dosage form are too small for all fluids compared to the in vivo situation. The lack of peristaltic contractions, which generate hydrodynamics and shear stress in vivo, might be the major drawback of the compendial device resulting in the observed differences between predicted and in vivo measured hydrodynamics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Formulation, optimization and evaluation of levocetirizine dihyrochloride oral thin strip

    Directory of Open Access Journals (Sweden)

    J Gunjan Patel

    2012-01-01

    Full Text Available The aim of present research was to develop a fast releasing oral polymeric film, with good mechanical properties, instant disintegration and dissolution, producing an acceptable taste when placed on tongue. Solvent casting method was used to prepare oral films. Levocetirizine dihydrochloride, an antihistaminic was incorporated to relieve the symptoms of allergic rhinitis. The polymers selected were HPMC E 15 and PVA. Propylene glycol was the plasticizers used. Nine batches of films with drug were prepared using different combinations of polymers and plasticizer concentration. The resultant films were evaluated for weight variation, content uniformity, folding endurance, thickness, surface pH, in vitro disintegration and in vitro dissolution. The optimized films which disintegrated in less than 30 sec, releasing 85-98% of drug within 2 minutes. The percentage release was varying with concentration of plasticizer and polymer. The films made with HPMC: PVA (1:2 released 96% of drug in 1 min, which was the best release amongst all.

  13. The effect of glicerol and sorbitol plasticizers toward disintegration time of phyto-capsules

    Science.gov (United States)

    Pudjiastuti, Pratiwi; Hendradi, Esti; Wafiroh, Siti; Harsini, Muji; Darmokoesoemo, Handoko

    2016-03-01

    The aim of research is determining the effect of glycerol and sorbitol toward the disintegration time of phyto-capsules, originated capsules from plant polysaccharides. Phyto-capsules were made from polysaccharides and 0.5% (v/v) of glycerol and sorbitol of each. The seven capsules of each were determined the disintegration time using Erweka disintegrator. The mean of disintegration time of phyto-capsules without plasticizers, with glycerol and sorbitol were 25'30"; 45'15" and 35'30" respectively. The color and colorless gelatin capsules showed the mean of disintegration time 7'30" and 2'35" respectively.

  14. Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle

    NARCIS (Netherlands)

    Borgdorff, Marinus A. J.; Bartelds, Beatrijs; Dickinson, Michael G.; Weij, Michel; Zandvoort, Andre; Sillje, Herman H. W.; Steendijk, Paul; de Vroomen, Maartje; Berger, Rolf M. F.; Boersma, B.

    Right ventricular (RV) failure due to pressure or volume overload is a major risk factor for early mortality in congenital heart disease and pulmonary hypertension, but currently treatments are lacking. We aimed to demonstrate that the phosphodiesterase 5A inhibitor sildenafil can prevent adverse

  15. Characterising the disintegration properties of tablets in opaque media using texture analysis.

    Science.gov (United States)

    Scheuerle, Rebekah L; Gerrard, Stephen E; Kendall, Richard A; Tuleu, Catherine; Slater, Nigel K H; Mahbubani, Krishnaa T

    2015-01-01

    Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. This study has explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (Pdisintegration times from each other in human versus bovine milk (adjusted P value 0.1685). Copyright © 2015 Elsevier B.V. All rights reserved.

  16. In vitro disintegration studies of weekly generic alendronate sodium tablets (70 mg) available in the US.

    Science.gov (United States)

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2009-02-01

    Bisphosphonates as a class have the potential to cause upper gastrointestinal irritation. Although the generic alendronate sodium tablets are bioequivalent to the branded product, a potential concern is that the pharmaceutical attributes of the various generic formulations my affect the potential for local irritation and tolerability. The in vitro disintegration times were determined using the method described in the US Pharmacopeia 30 (USP 30). The disintegration of three generic alendronate sodium tablets 70 mg available in the United States was compared to that of the branded product. The mean disintegration times of the generic alendronate sodium tablets ranged from 9 to 10 s for the Barr lots to 108 s for the Watson lot. The disintegration time of the branded product (Fosamax) was 53 s. The three Barr lots and one Teva lot had rapid disintegration times which were similar to the disintegration standards (disintegrating tablets. Since there is no established disintegration time for alendronate sodium tablets there can be no assurance that the generic tablets are equivalent to the branded product in terms of esophageal exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration performance. Copies of generic alendronate sodium tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not considered adequate to establish similar disintegration characteristics.

  17. Effect of sorbed water on disintegrant performance of four brands of Polacrilin Potassium NF.

    Science.gov (United States)

    Bele, Mrudula H; Derle, Diliprao V

    2012-03-01

    Polacrilin Potassium NF is a commonly used weak cation exchange resin disintegrant in pharmaceutical tablets. The objective of this research was to evaluate the effects of sorbed moisture on physical characteristics and disintegrant performance of four brands of Polacrilin Potassium NF. The disintegrants were stored in five different relative humidity chambers and their dynamic vapor adsorption-desorption analysis, effect of moisture on their compressibility, compactability, particle size, morphology, water uptake rate, and disintegration ability were studied. Moisture seemed to plasticize the disintegrants, reducing their yield pressures. However, certain optimum amount of moisture was found to be useful in increasing the compactablity of the tablets containing disintegrants. The tablets, however, lost their tensile strengths beyond this optimum moisture content. Moisture caused two brands of the disintegrants to swell; however, two other brands aggregated upon exposure to moisture. Swelling without aggregation increased the water uptake, and in turn the disintegrant performance. However, aggregation probably reduced the porosities of the disintegrants, reducing their water uptake rate and disintegrant performance. Different brands of Polacrilin Potassium NF differed in the abilities to withstand the effects of moisture on their functionality. Effect of moisture on disintegrant performance of Polacrilin Potassium NF needs to be considered before its use in tablets made by wet granulation.

  18. Assessment of disintegrant efficacy with fractal dimensions from real-time MRI.

    Science.gov (United States)

    Quodbach, Julian; Moussavi, Amir; Tammer, Roland; Frahm, Jens; Kleinebudde, Peter

    2014-11-20

    An efficient disintegrant is capable of breaking up a tablet in the smallest possible particles in the shortest time. Until now, comparative data on the efficacy of different disintegrants is based on dissolution studies or the disintegration time. Extending these approaches, this study introduces a method, which defines the evolution of fractal dimensions of tablets as surrogate parameter for the available surface area. Fractal dimensions are a measure for the tortuosity of a line, in this case the upper surface of a disintegrating tablet. High-resolution real-time MRI was used to record videos of disintegrating tablets. The acquired video images were processed to depict the upper surface of the tablets and a box-counting algorithm was used to estimate the fractal dimensions. The influence of six different disintegrants, of different relative tablet density, and increasing disintegrant concentration was investigated to evaluate the performance of the novel method. Changing relative densities hardly affect the progression of fractal dimensions, whereas an increase in disintegrant concentration causes increasing fractal dimensions during disintegration, which are also reached quicker. Different disintegrants display only minor differences in the maximal fractal dimension, yet the kinetic in which the maximum is reached allows a differentiation and classification of disintegrants. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.

    Science.gov (United States)

    Orejana, Lourdes; Barros-Miñones, Lucía; Jordan, Joaquin; Cedazo-Minguez, Angel; Tordera, Rosa M; Aguirre, Norberto; Puerta, Elena

    2015-06-01

    The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. © The Author 2014. Published by Oxford University Press on behalf of

  20. Sildenafil and tadalafil in simulated chlorination conditions: Ecotoxicity of drugs and their derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Temussi, Fabio; DellaGreca, Marina; Pistillo, Paola; Previtera, Lucio; Zarrelli, Armando [UdR Napoli 4 INCA, Dipartimento di Scienze Chimiche, Complesso Universitario di Monte Sant' Angelo, Università Federico II, Via Cintia, I-80126 Napoli (Italy); Criscuolo, Emma; Lavorgna, Margherita; Russo, Chiara [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Isidori, Marina, E-mail: marina.isidori@unina2.it [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy)

    2013-10-01

    Chlorination experiments on two drugs (sildenafil and tadalafil) were performed mimicking the conditions of a typical wastewater treatment process. The main transformation products were isolated by chromatographic techniques (Thin Layer Chromatography (TLC), Column Chromatography (CC), High Performance Liquid Chromatography (HPLC)) and fully characterized employing Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) analyses. The environmental effects of the parent compounds and transformation products were evaluated using an overall toxicity approach that considered aquatic acute and chronic toxicity on Brachionus calyciflorus and Ceriodaphnia dubia as well as mutagenesis and genotoxicity on bacterial strains. The results revealed that both parent drugs did not show high acute and chronic toxicity for the organisms utilized in the bioassays while, chronic exposure to chlorine derivatives caused inhibition of growth population on rotifers and crustaceans. A mutagenic potential was found for all the compounds investigated. - Highlights: • Simulated disinfection process of pharmaceuticals was performed. • Toxicity and genotoxicity of sildenafil, tadalafil and their derivatives were evaluated. • Chlorine derivatives caused chronic toxicity on rotifers and crustaceans. • A mutagenic potential was found for all the compounds investigated.

  1. Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

    Directory of Open Access Journals (Sweden)

    Leah A. Garcia

    2014-09-01

    Full Text Available Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG. Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1 β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1, and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH oxidase, Myeloperoxidase (MPO, inducible nitric oxide synthase (iNOS, TNF receptor superfamily member 5 (CD40 that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.

  2. Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila Seguimiento de dos años en pacientes con hipertensión arterial pulmonar bajo tratamiento con sildenafil Two-year follow-up of pulmonary arterial hypertension patients treated with sildenafil

    Directory of Open Access Journals (Sweden)

    Sonia Meiken Franchi

    2010-05-01

    Full Text Available FUNDAMENTO: Os efeitos de longo prazo das drogas desenvolvidas para o controle da hipertensão arterial pulmonar (HAP são pouco conhecidos, já que os estudos multicêntricos em geral têm duração de 12 a 16 semanas. OBJETIVO: Avaliar a evolução de dois anos, em pacientes com HAP submetidos à monoterapia com sildenafila (inibidor da fosfodiesterase-5, com respeito à capacidade funcional. MÉTODOS: Vinte e quatro pacientes (idade entre 8 e 54 anos com HAP idiopática (HAPI, n = 9 ou associada a cardiopatias congênitas (HAP-CCg, n = 15 foram tratados com sildenafila por dois anos, com doses diárias que variaram de 60 a 225 mg (três tomadas, por via oral. A capacidade física foi avaliada pela distância caminhada no teste de 6 minutos (DC6M e pelo grau de dispneia ao final da caminhada (escala de Borg, sendo também registrada a saturação periférica de oxigênio (SpO(26M, oximetria de pulso. RESULTADOS: Nos 18 pacientes que completaram dois anos de seguimento, houve incremento progressivo e sustentado na DC6M, tanto no grupo HAPI (de 239 ± 160 m para 471 ± 66 m, p = 0,0076 como no grupo HAP-CCg (de 361 ± 144 m para 445 ± 96m, p = 0,0031, com melhora da dispneia ao final da caminhada (p FUNDAMENTO: Los efectos a largo plazo de las drogas desarrolladas para el control de la hipertensión arterial pulmonar (HAP son poco conocidos, ya que los estudios multicéntricos en general tienen una duración de 12 a 16 semanas. OBJETIVO: Evaluar la evolución a dos años, en pacientes con HAP sometidos a monoterapia con sildenafil (inhibidor de la fosfodiesterasa-5, con respecto a la capacidad funcional. MÉTODOS: Veinticuatro pacientes (edades entre 8 y 54 años con HAP idiopática (HAPI, n = 9 o asociada a cardiopatías congénitas (HAP-CCg, n = 15 fueron tratados con sildenafil durante dos años, con dosis diarias que variaron de 60 a 225 mg (tres tomas, por vía oral. La capacidad física fue evaluada por la distancia caminada en el test de

  3. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

  4. Real-time microradiology of disintegration of iron ore sinteres

    International Nuclear Information System (INIS)

    Kim, Jong Ryun; Kang, H.S.; Lee, Ho Jun; Je, Jung Ho; Jeong, S.K.; Tsai, W.-L.; Hsu, P.C.; Hwu, Y.

    2003-01-01

    We first present real-time microradiology of disintegration of self-fluxing iron ore sinters in low temperature reduction using highly collimated synchrotron source. The experiments were performed on the 5C1 beamline at PLS (Pohang Light Source, Pohang, Korea), operating at 2.5 GeV. We used unmonochromatized ('white') light with no optical elements except beryllium windows. The images of the crack superimpose, on the two-dimensional projection of a three-dimensional phenomenon, suggest that cracks are always initiated from pores in the sinters and propagate along neighboring pores. Interestingly, cracking occurs mostly on macropores (>800 μm), preferentially initiated from stress concentrated sites on pore surfaces. This dynamic study of the disintegration of sinters clearly shows that the crack initiation temperature is as low as 450 deg. C

  5. Hydrothermal Disintegration and Extraction of Different Microalgae Species

    Directory of Open Access Journals (Sweden)

    Michael Kröger

    2018-02-01

    Full Text Available For the disintegration and extraction of microalgae to produce lipids and biofuels, a novel processing technology was investigated. The utilization of a hydrothermal treatment was tested on four different microalgae species (Scenedesmus rubescens, Chlorella vulgaris, Nannochloropsis oculata and Arthorspira platensis (Spirulina to determine whether it has an advantage in comparison to other disintegration methods for lipid extraction. It was shown, that hydrothermal treatment is a reasonable opportunity to utilize microalgae without drying and increase the lipid yield of an algae extraction process. For three of the four microalgae species, the extraction yield with a prior hydrothermal treatment elevated the lipid yield up to six times in comparison to direct extraction. Only Scenedesmus rubescens showed a different behaviour. Reason can be found in the different cell wall of the species. The investigation of the differences in cell wall composition of the used species indicate that the existence of algaenan as a cell wall compound plays a major role in stability.

  6. Disintegration of liquid metals by low pressure water blasting

    International Nuclear Information System (INIS)

    Heshmatpour, B.; Copeland, G.L.

    1981-01-01

    The feasibility of disintegrating metals by a low cost system and subsequently incorporating them into grout mixtures has been demonstrated. A low pressure water blasting technique consisting of multiple nozzles and a converging-line jet stream was developed to disintegrate liquid metals and produce coarse metal powder and shot. Molten iron resulted in spherical shot, while copper, aluminum, and tin produced irregular shaped particles. The particle size was between 0.05 and 3 mm (0.002 and 0.1 in.), and about half the particles were smaller than 1 mm (0.04 in.) in all cases. The water consumption was rather low, while the production rate was relatively high. The method proved to be simple and reliable. The coarse metal powders were suspendable in grout fluids, indicating that they are probably disposable by the shale hydrofracture technique

  7. Disintegration of rocks based on magnetically isolated high voltage discharge

    Science.gov (United States)

    He, Mengbing; Jiang, Jinbo; Huang, Guoliang; Liu, Jun; Li, Chengzu

    2013-02-01

    Recently, a method utilizing pulsed power technology for disintegration of rocks arouses great interest of many researchers. In this paper, an improved method based on magnetic switch and the results shown that the uniform dielectrics like plastic can be broken down in water is presented, and the feasible mechanism explaining the breakdown of solid is proposed and proved experimentally. A high voltage pulse of 120 kV, rise time 0.2 μs was used to ignite the discharging channel in solids. When the plasma channel is formed in the solid, the resistance of the channel is quiet small; even if a relatively low voltage is applied on the channel on this occasion, it will produce high current to heat the plasma channel rapidly, and eventually disintegrate the solids. The feasibility of promising industrial application in the drilling and demolition of natural and artificial solid materials by the method we presented is verified by the experiment result in the paper.

  8. Sarcoidosis-associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long-term effect of sildenafil

    DEFF Research Database (Denmark)

    Milman, Nils; Svendsen, Claus Bo; Iversen, Martin

    2009-01-01

    Abstract Background: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. Objectives: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil...

  9. Disintegration of Bone Cement by Continuous and Pulsating Water Jet

    Czech Academy of Sciences Publication Activity Database

    Hloch, S.; Foldyna, Josef; Sitek, Libor; Zeleňák, Michal; Hlaváček, Petr; Hvizdoš, P.; Kloc, J.; Monka, P.; Monková, K.; Kozak, D.; Magurová, D.

    2013-01-01

    Roč. 20, č. 4 (2013), s. 593-598 ISSN 1330-3651 R&D Projects: GA MŠk ED2.1.00/03.0082 Institutional support: RVO:68145535 Keywords : bone cement * disintegration * water jet Subject RIV: JQ - Machines ; Tools Impact factor: 0.615, year: 2013 http://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=157195

  10. Academic disintegrity among medical students: a randomised response technique study.

    Science.gov (United States)

    Mortaz Hejri, Sameh; Zendehdel, Kazem; Asghari, Fariba; Fotouhi, Akbar; Rashidian, Arash

    2013-02-01

    Medical students, as tomorrow's doctors, are responsible for their patients' health; cheating may affect their academic knowledge and clinical skills. The main purpose of this study was to investigate the frequency of and attitudes towards academic disintegrity among medical students at Tehran University of Medical Sciences (TUMS). Anonymous questionnaires including questions about various types of academic disintegrity were distributed among medical students during the clerkship and internship phases of the curriculum. Randomised response technique (RRT) was used to maintain the responders' privacy. Because the study design guaranteed the confidentiality of respondents, the TUMS Institutional Review Board declared that formal ethical approval was not required. A total of 124 students were enrolled in this study, of whom 63 were in the clerkship phase and 61 were in the internship phase. Of these respondents, 29% (n = 36) were male. The most frequently reported type of academic disintegrity was found to be 'impersonating an absent student in a class' (93%) and the least frequent to be 'legitimising absences by using bribes' (5%). Only a small number of interns considered 'buying hospital shifts', 'selling hospital shifts', 'impersonating an absent student' and 'helping others to cheat in examinations' as representing academic disintegrity. Approximately one third of participants stated that the RRT increased their confidence in anonymity and 90% of students found the use of RRT not difficult. Academic integrity is widely disrespected in different ways among medical students. Effective policies and interventions are required to control these misbehaviours in future doctors in order to optimise medical practice. Almost all respondents found it not difficult to use the RRT; the technique proved to be an effective and easily applied method of eliciting truthful responses to sensitive questions and represents an alternative to conventional anonymising techniques.

  11. The ability of the general male public to assess their suitability to take 50-mg sildenafil: an assessment of the comprehension of patient information materials via internet survey.

    Science.gov (United States)

    Symonds, Tara; Coyne, Karin S; Margolis, Mary Kay; Schnetzler, Gabriel

    2011-07-01

    Erectile dysfunction (ED) is the most common male sexual dysfunction and has a negative impact on masculinity and self-esteem. Phosphodiesterase type 5 inhibitors, including sildenafil, are the first-line treatment option for ED. Providing appropriate information regarding suitability for using sildenafil is important. The purpose of this study was to assess whether a broad spectrum of men could appropriately evaluate their suitability for 50-mg sildenafil after reviewing patient information materials. Patient information (Pack) on appropriate use of 50-mg sildenafil and patient information leaflet (PIL), a Web survey including demographics, self-assessed suitability for sildenafil use, and suitability screener. A randomly selected, population-representative Web-based panel of males in the UK was recruited for this study. Eligible men answered a brief sociodemographic questionnaire and then were presented with the Pack. If a participant desired additional information, he could also review the PIL. The participants then rated the Pack and PIL (if reviewed), self-assessed their suitability for sildenafil use, and completed a previously validated screener for suitability. A total of 1,275 men aged 40 and above were included in these analyses; the mean age was 57.8 ± 9.9 years. A total of 1,054 men reported ED; 517 men (40.5%) deemed themselves suitable for sildenafil; 504 men (39.6%) deemed themselves unsuitable; and 254 (19.9%) were unsure. The concordance rate between screener-assessed suitability and self-assessed suitability was 70.9% (95% confidence interval [CI] = 68.1-73.7%). When accounting for men who would not take sildenafil even though they were suitable or would seek additional information from a healthcare professional prior to using sildenafil, the concordance rate was 84.2% (95% CI = 82.2-86.2%). The results of this study suggest that men in the general population are capable of using written sildenafil patient education materials to accurately assess

  12. Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Sayeed, Vilayat A; Khan, Mansoor A

    2013-05-01

    Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. Copyright © 2013 Wiley Periodicals, Inc.

  13. In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada.

    Science.gov (United States)

    Walker, A D; Adachi, J D

    2011-09-01

    The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35 mg tablets compared to the innovator (branded) product, ACTONEL * *ACTONEL is a registered trade name of Warner Chilcott Company, LLC. (risedronate sodium) 35 mg. Tablets were inspected for colour and appearance. Disintegration times were determined using United States Pharmacopeia 33 (USP33-NF 28) methods. Disintegration onset time was also evaluated. The mean disintegration onset time values for the generic risedronate 35 mg tablets ranged from 2 to 29 seconds, and the mean disintegration completion times ranged from 81 to 260 seconds. The mean disintegration onset and completion time values for the ACTONEL 35 mg tablets were 23 and 43 seconds respectively. Four out of the five generic tablets tested had shorter disintegration onset times than the branded product; two of the generic tablet products had very fast disintegration onset times i.e. 2-3 seconds. Disintegration completion time for all five generic products tested was longer than that observed for the branded product; two generic products had disintegration completion time values five to six times longer than the branded product. Differences in the in vitro disintegration times were observed between the generic risedronate 35 mg tablets commercially available in Canada and the branded product, ACTONEL. The rapid disintegration onset times of two generic products may be important as this could increase the possibility of drug exposure in both the mouth and the esophagus during swallowing, resulting in unwanted localized irritation. However, it should be noted that an in vitro/in vivo correlation has not been established. Until such studies are completed it may be important to be aware of such in vitro disintegration differences when evaluating patients with newly presenting upper gastrointestinal complaints upon being switched from the branded product to generic formulations.

  14. Combined (alkaline+ultrasonic) pretreatment effect on sewage sludge disintegration.

    Science.gov (United States)

    Kim, Dong-Hoon; Jeong, Emma; Oh, Sae-Eun; Shin, Hang-Sik

    2010-05-01

    The individual effects of alkaline (pH 8-13) and ultrasonic (3750-45,000kJ/kg TS) pretreatments on the disintegration of sewage sludge were separately tested, and then the effect of combining these two methods at different intensity levels was investigated using response surface methodology (RSM). In the combined pretreatment, ultrasonic treatment was applied to the alkali-pretreated sludge. While the solubilization (SCOD/TCOD) increase was limited to 50% in individual pretreatments, it reached 70% in combined pretreatment, and the results clearly showed that preconditioning of sludge at high pH levels played a crucial role in enhancing the disintegration efficiency of the subsequent ultrasonic pretreatment. By applying regression analysis, the disintegration degree (DD) was fitted based on the actual value to a second order polynomial equation: Y=-172.44+29.82X(1)+5.30x10(-3)X(2)-7.53x10(-5)X(1)X(2)-1.10X(1)(2)-1.043x10(-7)X(2)(2), where X(1), X(2), and Y are pH, specific energy input (kJ/kg TS), and DD, respectively. In a 2D contour plot describing the tendency of DD with respect to pH and specific energy input, it was clear that DD increased as pH increased, but it seemed that DD decreased when the specific energy input exceeded about 20,000kJ/kg TS. This phenomenon tells us that there exists a certain point where additional energy input is ineffective in achieving further disintegration. A synergetic disintegration effect was also found in the combined pretreatment, with lower specific energy input in ultrasonic pretreatment yielding higher synergetic effect. Finally, in order to see the combined pretreatment effect in continuous operation, the sludge pretreated with low intensity alkaline (pH 9)/ultrasonic (7500kJ/kg TS) treatment was fed to a 3 L of anaerobic sequencing batch reactor after 70 days of control operation. CH(4) production yield significantly increased from 81.9+/-4.5mL CH(4)/g COD(added) to 127.3+/-5.0mL CH(4)/g COD(added) by pretreatment, and

  15. Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.

    Science.gov (United States)

    Musicki, Biljana; Champion, Hunter C; Becker, Robyn E; Liu, Tongyun; Kramer, Melissa F; Burnett, Arthur L

    2005-07-01

    Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats "primes" the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis.

  16. Mild disintegration of the green microalgae Chlorella vulgaris using bead milling.

    Science.gov (United States)

    Postma, P R; Miron, T L; Olivieri, G; Barbosa, M J; Wijffels, R H; Eppink, M H M

    2015-05-01

    In this work, the mild disintegration of the microalgae Chlorella vulgaris for the release of intracellular products has been studied. By means of bead milling the microalgae suspensions were successfully disintegrated at different biomass concentrations (25-145 gDW kg(-1)) over a range of agitator speeds (6-12 m s(-1)). In all cases over 97% of cell disintegration was achieved resulting in a release of water soluble proteins. A clear optimum rate of disintegration and protein release was observed at an agitator speed of 9-10 m s(-1) regardless of the biomass concentration. Selective extraction of water soluble proteins was observed as proteins released sooner than cell disintegration took place. Proteins could be released at 85% lower energy input than for cell disintegration resulting in specific energy consumptions well below 2.5 kWh kgDW(-1). Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates.

    Science.gov (United States)

    Olszynski, Wojciech P; Adachi, Jonathan D; Davison, K Shawn

    2014-01-01

    The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly (P disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies.

  18. Effect of turbulence on the disintegration rate of flushable consumer products.

    Science.gov (United States)

    Karadagli, Fatih; Rittmann, Bruce E; McAvoy, Drew C; Richardson, John E

    2012-05-01

    A previously developed model for the physical disintegration of flushable consumer products is expanded by investigating the effects of turbulence on the rate of physical disintegration. Disintegration experiments were conducted with cardboard tampon applicators at 100, 150, and 200 rotations per minute, corresponding to Reynold's numbers of 25,900, 39,400, and 52,900, respectively, which were estimated by using computational fluid dynamics modeling. The experiments were simulated with the disintegration model to obtain best-fit values of the kinetic and distribution parameters. Computed rate coefficients (ki) for all solid sizes (i.e., greater than 8, 4 to 8, 2 to 4, and 1 to 2 mm) increased strongly with Reynold's number or rotational speed. Thus, turbulence strongly affected the disintegration rate of flushable products, and the relationship of the ki values to Reynold's number can be included in mathematical representations of physical disintegration.

  19. Strategically functionalized carbon nanotubes as the ultrasensitive electrochemical probe for picomolar detection of sildenafil citrate (Viagra).

    Science.gov (United States)

    Gopalan, Anantha Iyengar; Lee, Kwang Pill; Komathi, Shanmugasundaram

    2011-02-15

    The present work demonstrates the utility of the functionalized carbon nanotubes, poly(4-aminobenzene sulfonic acid) (PABS) grafted multiwalled carbon nanotubes, MWNT-g-PABS, as an electrode modifier towards achieving ultrasensitive detection of a model drug, sildenafil citrate (SC). PABS units in MWNT-g-PABS interact with SC, pre-concentrate and accumulate at the surface. The electron transduction from SC to electrode is augmented via MWNT-g-PABS. As a result, the MWNT-g-PABS modified electrode exhibited ultrasensitive (57.7 μA/nM) and selective detection of SC with a detection limit of 4.7 pM. The present work provides scope towards targeting ultrasensitivity for the detection of biomolecules/drug through rational design and incorporation of appropriate chemical components to carbon nanotubes. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

    DEFF Research Database (Denmark)

    Pels, A; Kenny, L C; Alfirevic, Z

    2017-01-01

    randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants......BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate...... Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre...

  1. The use of hydrodynamic disintegration as a means to improve anaerobic digestion of activated sludge

    OpenAIRE

    Machnicka, A; Grűbel, K; Suschka, J

    2009-01-01

    Disintegration by hydrodynamic cavitation has a positive effect on the degree and rate of sludge anaerobic digestion. By applying hydrodynamic disintegration the lysis of cells occurs in minutes instead of days. The intracellular and extracellular components are set free and are immediately available for biological degradation which leads to an improvement of the subsequent anaerobic process. Hydrodynamic disintegration of the activated sludge results in organic matter and a polymer transfer ...

  2. Coherent electromagnetic excitation and disintegration of relativistic nuclei passing through crystals

    International Nuclear Information System (INIS)

    Pivovarov, Yu.L.; Shirokov, A.A.; Vorobiev, S.A.

    1990-01-01

    The energy dependence of electromagnetic excitation and electromagnetic disintegration cross sections for relativistic nuclei passing through crystals is investigated both theoretically and by means of computer simulation. For electromagnetic excitation, resonant peaks are found at definite energy values. An increase of electromagnetic excitation and disintegration cross sections in crystals at very high energies is found to be due to coherent addition of amplitudes. Numerical results are presented for the electric dipole excitation of fluorine nuclei and electromagnetic deuteron disintegration. (orig.)

  3. On the theory of deuteron disintegration with collective states excitation in nuclei

    International Nuclear Information System (INIS)

    Evlanov, M.V.

    1981-01-01

    Differential cross sections of diffraction disintegration of deuterons with excitation of collective states in nuclei have been theoretically investigated. Effects of nucleon-nucleon interaction as well as smearing of nucleus boundary on differential characteristics of deuteron disintegration accompanying with change in state of target- nuclei have been studied. Spectra of protons liberated during the reaction of 2 + level deuteron disintegration in 114 Cd nucleus are presented [ru

  4. IHF-independent assembly of the Tn10 strand transfer transpososome: implications for inhibition of disintegration

    OpenAIRE

    Stewart, Barry J.; Wardle, Simon J.; Haniford, David B.

    2002-01-01

    The frequency of DNA transposition in transposition systems that employ a strand transfer step may be significantly affected by the occurrence of a disintegration reaction, a reaction that reverses the strand transfer event. We have asked whether disintegration occurs in the Tn10 transposition system. We show that disintegration substrates (substrates constituting one half of the strand transfer product) are assembled into a transpososome that mimics the strand transfer intermediate. This str...

  5. Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution

    OpenAIRE

    Gupta, Abhay; Hunt, Robert L.; Shah, Rakhi B.; Sayeed, Vilayat A.; Khan, Mansoor A.

    2009-01-01

    The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegrat...

  6. Assessment of disintegrant efficacy with fractal dimensions from real-time MRI.

    OpenAIRE

    Quodbach, J.; Moussavi, A.; Tammer, R.; Frahm, J.; Kleinebudde, P.

    2014-01-01

    An efficient disintegrant is capable of breaking up a tablet in the smallest possible particles in the shortest time. Until now, comparative data on the efficacy of different disintegrants is based on dissolution studies or the disintegration time. Extending these approaches, this study introduces a method, which defines the evolution of fractal dimensions of tablets as surrogate parameter for the available surface area. Fractal dimensions are a measure for the tortuosity of a line, in this c...

  7. Tablet disintegration studied by high-resolution real-time magnetic resonance imaging.

    OpenAIRE

    Quodbach, J.; Moussavi, A.; Tammer, R.; Frahm, J.; Kleinebudde, P.

    2014-01-01

    The present work employs recent advances in high-resolution real-time magnetic resonance imaging (MRI) to investigate the disintegration process of tablets containing disintegrants. A temporal resolution of 75 ms and a spatial resolution of 80 x 80 m with a section thickness of only 600 m were achieved. The histograms of MRI videos were quantitatively analyzed with MATLAB. The mechanisms of action of six commercially available disintegrants, the influence of relative tablet density, and the i...

  8. Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Hosseini Sharifi

    2014-06-01

    Full Text Available Objective To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR with tamsulosin alone in patients with benign prostate hyperplasia (BPH. Materials and Methods 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4mg plus sildenafil 50mg in group A and tamsulosin 0.4mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient’s ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Results Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92. Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively. Fifteen patients in group A (success rate: 70% and nineteen patients in group B (success rate: 62.7% had failed trial without catheter (TWOC at 7th day following AUR (p value = 0.3. No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively. Conclusion It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

  9. Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention?

    Science.gov (United States)

    Sharifi, Seyed Hossein Hosseini; Mokarrar, Mohsen Heidari; Khaledi, Flora; Yamini-Sharif, Reyhaneh; Lashay, Alireza; Soltani, Mohammad Hossein

    2014-01-01

    To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention (AUR) with tamsulosin alone in patients with benign prostate hyperplasia (BPH). 101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012. Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4 mg plus sildenafil 50mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days. Urethral catheter was removed three days after medical treatment and patient's ability to void assessed at the day after catheter removal and seven days later. Patients who voided successfully were followed at least for three months. Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B (p value = 0.92). Mean prostate volume and mean residual urine were comparable between both groups (p value = 0.74 and 0.42, respectively). Fifteen patients in group A (success rate: 70%) and nineteen patients in group B (success rate: 62.7%) had failed trial without catheter (TWOC) at 7th day following AUR (p value = 0.3). No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period (p = 0.07 and p = 0.45, respectively). It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone.

  10. Ultrasonically enhanced disintegration. Polymers, sludge, and contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Groenroos, A.

    2010-05-15

    There are a great variety of potential applications of high-intensity ultrasonic energy. Of these, cleaning, plastic pounding, and at present also sludge disintegration and the remediation of contaminated soil are probably the best known and offer the most general market for high-intensity ultrasonics. All developments within the area of ultrasound applications lead to the creation of environmentally friendly processes and compounds, emphasizing the role of ultrasound in 'green chemistry'. Ultrasound technology is considered not easy to use in industrial processes, since devices providing high sonic energy are not easy to construct. This thesis investigates on a semi-pilot scale if it is possible to enhance the disintegration of three quite different samples: polymers, sludge, and contaminated soil by using ultrasound. The results indicate that it is possible to enhance the disintegration of polymers by means of ultrasonic power only when the cavitation threshold is exceeded. Above the cavitation threshold, the most extensive degradation took place at the lowest ultrasonic frequency used. The biggest decrease (from 115,000 g/mol to 30,000 g/mol) in relative molecular mass (RMM) was observed when the concentration of polyvinyl alcohol (PVA) was the lowest (1.0%). However, in the case of carboxymethylcellulose (CMC) it was observed that when viscosity was not adjusted there is an optimum polymer concentration (1.5-2.0%) where degradation is most efficient. The thesis shows that the extent of ultrasonic depolymerization decreases with decreasing molecular mass of the CMC polymer. The study also reveals that ultrasonic irradiation causes narrowing of the molecular mass distribution. The degradation of CMC polymer proceeded linearly and the rate of ultrasonic depolymerization decreased with decreasing molecular mass. In cases where the initial dynamic viscosities of polymer solutions were not the same, the sonolytic degradation of CMC polymer mainly depended

  11. Correlation of dissolution and disintegration results for an immediate-release tablet.

    Science.gov (United States)

    Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

    2018-02-20

    The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Investigation of the exclusive light-ion disintegration processes on the basis of a diffraction model

    International Nuclear Information System (INIS)

    Evlanov, M.V.; Sokolov, A.M.

    1986-01-01

    A diffraction approach is developed for description of kinematically complete experiments on the disintegration on nuclei with diffuse edges of light, weakly bound ions consisting of one neutral and one charged cluster. The theoretical formalism is used to analyze exclusive experiments on deuteron disintegration in the region of intermediate energies and for a broad range of nuclear mass numbers with a view to studying the structural characteristics of the nuclei and the mechanisms underlying the disintegration process. The possibility of the occurrence of the Nemets effect in the case of the disintegration of other (not only deuterons) light, weakly bound ions on nuclei is discussed

  13. About factors of disintegration of nonideal plasma at explosion of the tungstic conductor in water

    International Nuclear Information System (INIS)

    Fedorovich, O.A.; Vojtenko, L.M.

    2010-01-01

    Results of experimental definition of disintegration coefficient of the nonideal plasma, formed at explosion of tungsten wires in water, are resulted. Disintegration coefficient are investigated at electron density from 10 20 cm-3 to 5,5 · 10 21 cm -3 . With reduction of concentration in the indicated electron density range disintegration coefficients increase from 4 · 10 -18 to 1 · 10 -15 cm 3 /s at brightness temperature (7...10) ·10 3 K. Supposed mechanisms of increase in disintegration coefficient with reduction of electron concentration are presented.

  14. Study on exclusive processes of light ion disintegration in the framework of diffraction model

    International Nuclear Information System (INIS)

    Evlanov, M.V.; Sokolov, A.M.

    1986-01-01

    A diffraction approach is developed for description of kinematically complete experiments on disintegration of light weakly-bound ions formed by two clusters (one being charged) on nuclei with diffused edge. The theoretical formalism is applied to analyze exclusive deuteron disintegration experiments at intermediate energies for a wide nuclear mass numbers. The aim of the analysis is to study structure peculiarities of nuclei and disintegration mechanisms. Possible existence of the Nemets effect is discussed for disintegration of other than deuterons weakly-bound ions by nuclei

  15. A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

    Science.gov (United States)

    Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

    2015-11-01

    No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Prediction of tablets disintegration times using near-infrared diffuse reflectance spectroscopy as a nondestructive method.

    Science.gov (United States)

    Donoso, M; Ghaly, Evone S

    2005-01-01

    The goals of this study are to user near-infrared reflectance (NIR) spectroscopy to measure the disintegration time of a series of tablets compacted at different compressional forces, calibrate NIR data vs. laboratory equipment data, develop a model equation, validate the model, and test the model's predictive ability. Seven theophylline tablet formulations of the same composition but with different disintegration time values (0.224, 1.141, 2.797, 5.492, 9.397, 16.8, and 30.092 min) were prepared along with five placebo tablet formulations with different disintegration times. Laboratory disintegration time was compared to near-infrared diffuse reflectance data. Linear regression, quadratic, cubic, and partial least square techniques were used to determine the relationship between disintegration time and near-infrared spectra. The results demonstrated that an increase in disintegration time produced an increase in near-infrared absorbance. Series of model equations, which depended on the mathematical technique used for regression, were developed from the calibration of disintegration time using laboratory equipment vs. the near-infrared diffuse reflectance for each formulation. The results of NIR disintegration time were similar to laboratory tests. The near-infrared diffuse reflectance spectroscopy method is an alternative nondestructive method for measurement of disintegration time of tablets.

  17. Ozone disintegration kinetics in the reactor for tyres decomposition

    International Nuclear Information System (INIS)

    Golota, V.I.; Manujlenko, O.V.; Taran, G.V.; Pis'menetskij, A.S.; Zamuriev, A.A.

    2010-01-01

    The results of theoretical and experimental research of ozone disintegration kinetics in the chemical reactor which is developed for decomposition of tyres in the ozone-air environment are presented. Analytical expression for dependence of ozone concentration in the reactor from time and from parameters of the task, such as volume speed of ozone-air mixture feed on a reactor input, concentration of ozone on the input to the reactor, volume speed of output of the used mixture, reactor size, and square of its internal surface is obtained. It is shown that at the same speed of ozone-air mixture pro rolling through the reactor, with growth of ozone concentration on the input, value of stationary concentration in the reactor grows, remaining always less than concentration on the input. It is also shown that at the same ozone concentration on the input, with growth of speed of ozone-air mixture pro rolling through the reactor, value of stationary ozone concentration in the reactor also grows, remaining always less than ozone concentration on the input. The ozone disintegration kinetics in the reactor in a wide range of speed of ozone-air mixture pro rolling through the reactor (0.15, 0.30, 0.45, 0.60 m3/hour) and various ozone concentration on the input (5, 10, 15, 20 g/m3) is experimentally studied. It is shown that experimental results with good accuracy coincide with the theoretical. Direct experiment showed the essential influence of the internal surface of the reactor on the ozone disintegration kinetics.

  18. The Mechanism of Disintegration of Cement Concrete at High Temperatures

    Directory of Open Access Journals (Sweden)

    Jocius Vytautas

    2016-10-01

    Full Text Available Concrete is a composite material composed of a binder, aggregates, water and additives. Mixing of cement with water results in a number of chemical reactions known as cement hydration. Heating of concrete results in dehydration processes of cement minerals and new hydration products, which disintegrate the microstructure of concrete. This article reviews results of research conducted with Portland and alumina cement with conventional and refractory concrete aggregates. In civic buildings such common fillers as gravel, granite, dolomite or expanded clay are usually used. It is important to point out the differences between fillers because they constitute the majority of the concrete volume.

  19. Dosimetric measurement of the disintegration rate of fission products

    International Nuclear Information System (INIS)

    Solymosi, J.; Nagy, L.G.; Zagyvai, P.

    1992-01-01

    Investigations on the disintegration rate of fission products of 238 U and 239 Pu are presented. The intensity of the β-and γ-radiation of fission products were measured continously in an interval of 1-1300 hours following the fission, offering the possibility for determining the general and specific characteristics of the individual fission products. A universal measuring procedure was elaborated for the rapid in situ determination of the dosimetric features of fission products, which is suitable for the accurate evaluation and prediction of external absorbed dose even in case of fission products of various origin and unknown composition. (author) 6 refs.; 7 figs.; 1 tab

  20. Disintegration and dimerization of δ-tocopherol under radiation effect

    International Nuclear Information System (INIS)

    Jasinska-Stepniak, A.; Gogolewski, M.; Zabielski, J.

    1996-01-01

    The goal of the work was to recognize scala changes of δ-tocopherol in model system (diluted in benzene, ethanol and ''in substantia'') after 2.5, 5, 10 and 20 kGy dose irradiation. δ-tocopherol and its mild oxidation products (dimers) after TLC separation were quantitatively determined with Emmerie-Engel method. Relations dose-effect have been defined and radiation capacity has been calculated. The results show that disintegration of δ-tocopherol diluted in ethanol is about ten times stronger the diluted in benzene. δ-tocopherol in benzene was dimerized. The most stable after irradiation was δ-tocopherol ''in substantia''. (author)

  1. Monitoring of Acoustic Emission During the Disintegration of Rock

    Czech Academy of Sciences Publication Activity Database

    Tripathi, R.; Srivastava, M.; Hloch, Sergej; Adamčík, P.; Chattopadhyaya, S.; Das, A. K.

    2016-01-01

    Roč. 149, č. 149 (2016), s. 481-488 E-ISSN 1877-7058. [International Conference on Manufacturing Engineering and Materials, ICMEM 2016. Nový Smokovec, 06.06.2016-10.06.2016] R&D Projects: GA MŠk ED2.1.00/03.0082; GA MŠk(CZ) LO1406 Institutional support: RVO:68145535 Keywords : acoustic emission * rock disintegration * waterjet Subject RIV: JQ - Machines ; Tools http://www.sciencedirect.com/science/article/pii/S1877705816312127

  2. A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil

    Directory of Open Access Journals (Sweden)

    Felekis T

    2011-10-01

    Full Text Available T Felekis1, I Asproudis1, K Katsanos2, EV Tsianos21University Eye Clinic of Ioannina, Ioannina, Greece; 2First Department of Internal Medicine, University Hospital of Ioannina, Ioannina, GreeceAbstract: A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION 12 hours after receiving sildenafil citrate (Viagra®. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs.Keywords: sildenafil, nonarteritic anterior ischemic optic neuropathy, erectile dysfunction drugs, family history

  3. Safety and long-term efficacy of transition from sildenafil to tadalafil due to side effects in patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Lichtblau, Mona; Harzheim, Dominik; Ehlken, Nicola; Marra, Alberto; Pinado, Fabiola Pena; Grünig, Ekkehard; Egenlauf, Benjamin

    2015-02-01

    Two phosphodiesterase-type 5 (PDE-5) inhibitors, sildenafil and tadalafil, are approved for treatment of pulmonary arterial hypertension (PAH). It has not yet been observed if transition from sildenafil to tadalafil is beneficial in patients suffering from adverse reactions. Aim of this study was to analyze safety and long-term effects in PAH patients whose treatment was transitioned from sildenafil to tadalafil due to intolerable side-effects. A retrospective analysis of PAH-patients who were stable on sildenafil for >3 months and transitioned to tadalafil due to adverse events was performed. Data collected included demographics, PAH-etiology, WHO-functional class, 6 min walking distance (6MWD), echocardiography, lung function tests, and NTproBNP pre-transition and 3, 6, and 12 months post-transition. Included were 13 PAH patients (8 females mean age 64 ± 10 years) who had been on sildenafil for a mean of 12 ± 8.4 months. In six patients (46.1 %) a switch to tadalafil was feasible and resulted in tolerable side effects and a stable clinical course with improvement of symptoms, 6MWD, stable echocardiographic findings, and NTproBNP-levels during a follow-up of 11 ± 3 months. In 5 out of 13 patients (38.5 %) adverse events occurred under tadalafil as well and therapy with PDE-5 inhibitors was discontinued. In two patients (15.4 %) sildenafil-treatment could be successfully restarted after an intermittent switch to tadalafil. The observations of this study indicate that a transition of sildenafil to tadalafil in case of intolerable side effects is a reasonable therapy option in about 50 % of the patients. These results should be verified by a larger prospective study.

  4. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    Science.gov (United States)

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  5. Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets.

    Science.gov (United States)

    Silvera, F E; Blasina, M F; Vaamonde, L; Tellechea, S; Godoy, C; Zabala, S; Mañana, G; Martell, M; Olivera, W

    2011-08-01

    Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

  6. The use of sildenafil in the treatment of persistent pulmonary hypertension of the newborn: a review of the literature.

    Science.gov (United States)

    Iacovidou, Nicoletta; Syggelou, Aggeliki; Fanos, Vassilios; Xanthos, Theodoros

    2012-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a serious and potentially fatal condition, characterized by hypoxemia due to increased pulmonary vascular resistance (PVR) with resultant shunting of pulmonary blood to the systemic circulation. Inhaled nitric oxide (iNO) has been considered a revolutionary treatment of PPHN. Data show that the use of iNO has reduced the need of ECMO in neonates with severe PPHN, while in moderate PPHN, iNO administration has been associated with a significant decrease in ventilatory support and prevented progression to severe PPHN. Not all neonates respond to iNO therapy though, and phosphodiesterase (PDE) inhibitors with their potent vasodilator properties have evolved as an alternative therapy or as an adjunct to the treatment of PPHN with iNO. There are ten families of PDE isoenzymes. PDE 5 is particularly prevalent in vascular smooth muscle (VSM) and PDE 5 inhibitors, such as sildenafil, have been used in clinical practice. This review provides a comprehensive account of existing data in the literature, from animal and clinical studies, on the use of sildenafil for the treatment of PPHN. Sildenafil may also have a role as a single mode of therapy, since in resource-limited settings the cost of iNO is a serious concern.

  7. Biological effects of disintegration of electrocaptured radionuclides: the role of physical characteristics of disintegration and distribution of the absorbed dose

    International Nuclear Information System (INIS)

    Stepanenko, V.F.

    1979-01-01

    Problems pertaining to the internal irradiation by radionuclides radiating during the disintegration according to the electron capture scheme a great amount of low-energy monoenergetic electrons (Auger electrons, internal conversion electrons) are considered. Main attention has been paid to the role of low-energy electrons and transmutation effects in the selective injury of intranuclear sensitive locuses as well as to the importance of the character of absorption dose distribution over the tissue microstructures. It is shown that very promising seems to be in principle the possibility of using electronradiating atoms for the radiotherapy purposes

  8. Critical operational parameters for zero sludge production in biological wastewater treatment processes combined with sludge disintegration.

    Science.gov (United States)

    Yoon, Seong-Hoon; Lee, Sangho

    2005-09-01

    Mathematical models were developed to elucidate the relationships among process control parameters and the effect of these parameters on the performance of anoxic/oxic biological wastewater processes combined with sludge disintegrators (A/O-SD). The model equations were also applied for analyses of activated sludge processes hybrid with sludge disintegrators (AS-SD). Solubilization ratio of sludge in the sludge disintegrator, alpha, hardly affected sludge reduction efficiencies if the biomass was completely destructed to smaller particulates. On the other hand, conversion efficiency of non-biodegradable particulates to biodegradable particulates, beta, significantly affected sludge reduction efficiencies because beta was directly related to the accumulation of non-biodegradable particulates in bioreactors. When 30% of sludge in the oxic tank was disintegrated everyday and beta was 0.5, sludge reduction was expected to be 78% and 69% for the A/O-SD and AS-SD processes, respectively. Under this condition, the sludge disintegration number (SDN), which is the amount of sludge disintegrated divided by the reduced sludge, was calculated to be around 4. Due to the sludge disintegration, live biomass concentration decreased while other non-biodegradable particulates concentration increased. As a consequence, the real F/M ratio was expected to be much higher than the apparent F/M. The effluent COD was maintained almost constant for the range of sludge disintegration rate considered in this study. Nitrogen removal efficiencies of the A/O-SD process was hardly affected by the sludge disintegration until daily sludge disintegration reaches 40% of sludge in the oxic tank. Above this level of sludge disintegration, autotrophic biomass concentration decreases overly and TKN in the effluent increases abruptly in both the A/O-SD and AS-SD processes. Overall, the trends of sludge reduction and effluent quality according to operation parameters matched well with experimental results

  9. Comparison between ozone and ultrasound disintegration on sludge anaerobic digestion.

    Science.gov (United States)

    Braguglia, C M; Gianico, A; Mininni, G

    2012-03-01

    This paper deals with the comparison of ultrasound (mechanical) and ozone (chemical) pre-treatment on the performances of excess sludge semi-continuous digestion. Sludge solubilisation has been investigated by varying specific energy input. For each pre-treatment, long anaerobic digestion tests were carried out by two parallel digesters: one reactor, as control unit, was fed with untreated waste activated sludge, and the other one was fed with disintegrated sludge. To evaluate and compare the efficacy of both pre-treatments, the specific energy was maintained approximately the same. The digestion tests were carried out to investigate the feasibility of anaerobic digestion performance (total biogas production, volatile solids removal, sludge dewaterability) and to assess the heat balance. Results obtained from the digestion of sonicated sludge at 4% disintegration degree (≈ 2500 kJ/kg TS) showed that the ultrasound pre-treatment may be effective both in increasing VS destruction (+19%) and cumulative biogas production (+26%). On the contrary, the digestion test with ozonized sludge (ozone dose of 0.05 g O(3)/g TS corresponding to ≈ 2000 kJ/kg TS) did not indicate a significant improvement on the digestion performances. By doubling the ozone dose an improvement in the organics removal and cumulative biogas production was observed. Relevant differences in terms of colloidal charge and filterability were discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Electrohydrodynamic Liquid Disintegration in Micro-, Meso- and Nanoscopic Dimensions

    Science.gov (United States)

    Vertes, Akos

    2008-11-01

    The electrohydrodynamic dispersion of liquids spans length scales from 1 mm to 1 nm and involves temporal variations from 1 s to 10 ps. The disintegration mechanisms are diverse and, due to the differences in the dominating forces, vary on the micro-, meso- and nanoscale extending to lower boundaries of 1 μm, 10 nm and 1 nm, respectively. Using fast imaging, spray current measurements, phase Doppler anemometry and molecular dynamics calculations, we followed the behavior of electrified liquids in the three most common geometries, spherical, pendant drop and slender jet, with dimensions ranging from 100 μm to 1 nm. Microscale disintegration involves jet ejection from conical surface deformations, jet breakup due to varicose, kink and ramified jet instabilities, and asymmetric droplet fission resulting in side jets. As the liquid dimensions shift from the microscopic dimensions where the processes are governed by the surface tension and the Maxwell stress, to the meso- and nanoscale, thermal fluctuations become increasingly important. The presence of charges in nanodroplets leads to enhanced surface fluctuations, the formation of extreme protrusions and eventually solvated ion evaporation. Charging of slender nanojets results in longer shape relaxation times along with the fission of systems charged below the Rayleigh limit. In collaboration with Jelena Lusic and Peter Nemes, George Washington University.

  11. Neuronal network disintegration: common pathways linking neurodegenerative diseases.

    Science.gov (United States)

    Ahmed, Rebekah M; Devenney, Emma M; Irish, Muireann; Ittner, Arne; Naismith, Sharon; Ittner, Lars M; Rohrer, Jonathan D; Halliday, Glenda M; Eisen, Andrew; Hodges, John R; Kiernan, Matthew C

    2016-11-01

    Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Effect of polacrilin potassium as disintegrant on bioavailability of diclofenac potassium in tablets : a technical note.

    Science.gov (United States)

    Bele, Mrudula H; Derle, Diliprao V

    2012-09-01

    Polacrilin potassium is an ion exchange resin used in oral pharmaceutical formulations as a tablet disintegrant. It is a weakly acidic cation exchange resin. Chemically, it is a partial potassium salt of a copolymer of methacrylic acid with divinyl benzene. It ionizes to an anionic polymer chain and potassium cations. It was hypothesized that polacrilin potassium may be able to improve the permeability of anionic drugs according to the Donnan membrane phenomenon. The effect of polacrilin potassium on the permeability of diclofenac potassium, used as a model anionic drug, was tested in vitro using diffusion cells and in vivo by monitoring serum levels in rats. The amount of drug permeated across a dialysis membrane in vitro was significantly more in the presence of polacrilin potassium. Significant improvement was found in the extent of drug absorption in vivo. It could be concluded that polacrilin potassium may be used as a high-functionality excipient for improving the bioavailability of anionic drugs having poor gastrointestinal permeability.

  13. STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis

    NARCIS (Netherlands)

    Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N.

    2014-01-01

    In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these

  14. Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill.

    Science.gov (United States)

    Pan, Zhidong; Huang, Ying; Wang, Yanmin; Wu, Zhiwei

    2017-12-01

    The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3-0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bio-predictive tablet disintegration: effect of water diffusivity, fluid flow, food composition and test conditions.

    Science.gov (United States)

    Radwan, Asma; Wagner, Manfred; Amidon, Gordon L; Langguth, Peter

    2014-06-16

    Food intake may delay tablet disintegration. Current in vitro methods have little predictive potential to account for such effects. The effect of a variety of factors on the disintegration of immediate release tablets in the gastrointestinal tract has been identified. They include viscosity of the media, precipitation of food constituents on the surface of the tablet and reduction of water diffusivity in the media as well as changes in the hydrodynamics in the surrounding media of the solid dosage form. In order to improve the predictability of food affecting the disintegration of a dosage form, tablet disintegration in various types of a liquefied meal has been studied under static vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and Reynolds numbers for the different media were characterized. A quantitative model is introduced which predicts the influence of the Reynolds number in the tablet disintegration apparatus on the disintegration time. Viscosity, water diffusivity and media flow velocity are shown to be important factors affecting dosage form disintegration. The results suggest the necessity of considering these parameters when designing a predictive model for simulating the in vivo conditions. Based on these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is concluded that the disintegration tester under current pharmacopoeial conditions is operated in an unphysiological mode and no bioprediction may be derived. Recommendations regarding alternative mode of operation are made. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield.

    Science.gov (United States)

    Shehu, Muhammad Sani; Abdul Manan, Zainuddin; Alwi, Sharifah Rafidah Wan

    2012-06-01

    Optimization of thermo-alkaline disintegration of sewage sludge for enhanced biogas yield was carried out using response surface methodology (RSM) and Box-Behnken design of experiment. The individual linear and quadratic effects as well as the interactive effects of temperature, NaOH concentration and time on the degree of disintegration were investigated. The optimum degree of disintegration achieved was 61.45% at 88.50 °C, 2.29 M NaOH (24.23%w/w total solids) and 21 min retention time. Linear and quadratic effects of temperature are most significant in affecting the degree of disintegration. The coefficient of determination (R(2)) of 99.5% confirms that the model used in predicting the degree of disintegration process has a very good fitness with the experimental variables. The disintegrated sludge increased the biogas yield by 36%v/v compared to non-disintegrated sludge. The RSM with Box-Behnken design is an effective tool in predicting the optimum degree of disintegration of sewage sludge for increased biogas yield. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. A novel mechanism for J/ψ disintegration in relativistic heavy ion collisions

    International Nuclear Information System (INIS)

    Atreya, Abidshek; Bagchi, Partha; Srivastava, Ajit M.

    2015-01-01

    In this paper we discuss the possibility of J/ψ disintegration due to the Z (3) domain walls that are expected to form in QGP medium. These domain walls give rise to localised color electric field which disintegrates J/ψ, on interaction, by changing the color composition and simultaneously exciting it to higher states of cc-bar system. (author)

  18. Physical disintegration of toilet papers in wastewater systems: experimental analysis and mathematical modeling.

    Science.gov (United States)

    Eren, Beytullah; Karadagli, Fatih

    2012-03-06

    Physical disintegration of representative toilet papers was investigated in this study to assess their disintegration potential in sewer systems. Characterization of toilet papers from different parts of the world indicated two main categories as premium and average quality. Physical disintegration experiments were conducted with representative products from each category according to standard protocols with improvements. The experimental results were simulated by mathematical model to estimate best-fit values of disintegration rate coefficients and fractional distribution ratios. Our results from mathematical modeling and experimental work show that premium products release more amounts of small fibers and disintegrate more slowly than average ones. Comparison of the toilet papers with the tampon applicators studied previously indicates that premium quality toilet papers present significant potential to persist in sewer pipes. Comparison of turbulence level in our experimental setup with those of partial flow conditions in sewer pipes indicates that drains and small sewer pipes are critical sections where disintegration of toilet papers will be limited. For improvement, requirements for minimum pipe slopes may be increased to sustain transport and disintegration of flushable products in small pipes. In parallel, toilet papers can be improved to disintegrate rapidly in sewer systems, while they meet consumer expectations.

  19. Diffraction scattering and disintegration of 3He nuclei by atomic nuclei

    International Nuclear Information System (INIS)

    Koval'chuk, V.I.

    2006-01-01

    Within diffraction model framework a method of cross sections calculation for scattering and disintegration of weakly-bounded two-clustered nuclei by nuclei when both of its clusters are changed has been proposed. The experimental elastic scattering cross sections of 3 He by 40 Ca, 90 Zr and coincidence spectra of disintegration products from 28 Si( 3 He,dp) have been described

  20. Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

    Science.gov (United States)

    Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

    2013-01-01

    Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

  1. Mild disintegration of the green microalgae Chlorella vulgaris using bead milling

    NARCIS (Netherlands)

    Postma, P.R.; Miron, T.L.; Olivieri, G.; Barbosa, M.J.; Wijffels, R.H.; Eppink, M.H.M.

    2015-01-01

    In this work, the mild disintegration of the microalgae Chlorella vulgaris for the release of intracellular products has been studied. By means of bead milling the microalgae suspensions were successfully disintegrated at different biomass concentrations (25–145 gDW kg-1) over a range of agitator

  2. Analysis of illicit dietary supplements sold in the Italian market: identification of a sildenafil thioderivative as adulterant using UPLC-TOF/MS and GC/MS.

    Science.gov (United States)

    Damiano, Fabio; Silva, Claudia; Gregori, Adolfo; Vacondio, Federica; Mor, Marco; Menozzi, Mattia; Di Giorgio, Domenico

    2014-05-01

    Identification of pharmaceutical active ingredients sildenafil and tadalafil and the characterization of a dimethylated thio-derivative of sildenafil, called thioaildenafil or thiodimethylsildenafil, in illicit dietary supplements were described. A multi-residual ultra-performance liquid chromatography-time of flight mass spectrometry (UPLC-TOF/MS) method was developed to screen for the presence of the phosphodiesterase-5 (PDE-5) inhibitors sildenafil, tadalafil, and vardenafil and their analogues thioaildenafil and thiohomosildenafil in powders and pharmaceutical dosage forms. The study was developed in connection with an operation supervised by the Italian Medicines Agency (A.I.F.A.), aimed to monitor dietary supplements in the Italian market. In two of the eleven specimens under investigation, high-resolution mass spectrometry (HR-MS) allowed the identification of the PDE-5 inhibitors sildenafil and tadalafil, while another specimen proved to contain a unapproved dimethylated thioderivative of sildenafil, thioaildenafil or thiodimethylsildenafil, identified for the first time in Italy as adulterant in food supplements. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study

    International Nuclear Information System (INIS)

    Incrocci, Luca; Koper, Peter C.M.; Hop, Wim C.J.; Slob, A. Koos

    2001-01-01

    Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer

  4. Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

    2006-07-01

    Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

  5. Histological evaluation of the rat dental pulp after indirect capping with sildenafil or L-NAME incorporated into a bioadhesive thermoresponsive system

    Directory of Open Access Journals (Sweden)

    Rogério Rodrigues Cupertino

    2016-06-01

    Full Text Available We evaluated the histological dental pulp state in vivo after indirect pulp capping using sildenafil or LG-nitro-L-arginine (L-NAME, incorporated into a new bioadhesive thermoresponsive system (BTS. Male Wistar rats were subjected to an upper and lower first molar class I cavity preparation followed by indirect pulp capping with sildenafil or L-NAME. Calcium hydroxide (CaOH2 was used as a control. The teeth and surrounding bone were properly dissected and processed for Nissl’s staining. Pulp state was evaluated considering the morphological aspects of the inflammatory response, type of inflammatory infiltrate, organization of the odontoblast layer, blood vessel condition, and presence of abscesses or necrosis. The results were expressed as average of observations. The most intense inflammatory response was observed 3 days after the cavity preparation. No identified changes were detected in the dental pulp response of the molars treated with L-NAME compared with those treated with CaOH2. A dual effect was observed in the teeth treated with sildenafil. While low sildenafil concentration (0.015% w w-1 promoted effects comparable to CaOH2, at a higher concentration (0.15% w w-1, sildenafil caused a severe inflammatory response and pulp necrosis. This pioneering suggest that NO pathway activity may be a determinant in the process of dental pulp healing.

  6. Sildenafil citrate improves self-esteem, confidence, and relationships in men with erectile dysfunction: Results from an international, multi-center, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Althof, Stanley E; O'leary, Michael P; Cappelleri, Joseph C; Hvidsten, Kyle; Stecher, Vera J; Glina, Sidney; King, Rosie; Siegel, Richard L

    2006-05-01

    Erectile dysfunction (ED) can significantly impact a man's relationships and well-being. We assessed changes in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction in men with ED using the validated Self-Esteem And Relationship questionnaire (SEAR). This was a 12-week, double-blind, placebo-controlled, flexible-dose (25, 50, 100 mg, as needed) international study of sildenafil in men > or =18 years of age in Mexico, Brazil, Australia, and Japan. The primary study outcome was change in self-esteem from baseline to the end of treatment. Secondary study measures were changes in other SEAR components, International Index of Erectile Function (IIEF) domains, percentage of intercourse attempts that were successful, and the response to a global efficacy question at the end of treatment. Patients were well balanced for age and duration of ED (placebo = 149 and sildenafil = 151). Compared with placebo, sildenafil significantly improved self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction (P relationship satisfaction, and overall relationship satisfaction after treatment of ED with sildenafil were consistent among countries. These data suggest a substantial cross-cultural improvement in well-being after successful treatment of ED with sildenafil.

  7. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma

    Science.gov (United States)

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  8. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  9. [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

    NARCIS (Netherlands)

    Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

    2006-01-01

    The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

  10. Disintegration of excess activated sludge--evaluation and experience of full-scale applications.

    Science.gov (United States)

    Zábranská, J; Dohányos, M; Jenícek, P; Kutil, J

    2006-01-01

    Anaerobic digestion of sewage sludge can be improved by introducing a disintegration of excess activated sludge as a pretreatment process. The disintegration brings a deeper degradation of organic matter and less amount of output sludge for disposal, a higher production of biogas and consequently energy yield, in some cases suppression of digesters foaming and better dewaterability. The full-scale application of disintegration by a lysate-thickening centrifuge was monitored long term in three different WWTPs. The evaluation of contribution of disintegration to biogas production and digested sludge quality was assessed and operational experience is discussed. Increment of specific biogas production was evaluated in the range of 15-26%, organic matter in digested sludge significantly decreased to 48-49%. Results proved that the installation of a disintegrating centrifuge in WWTPs of different sizes and conditions would be useful and beneficial.

  11. Childhood disintegrative disorder: distinction from autistic disorder and predictors of outcome.

    Science.gov (United States)

    Rosman, N Paul; Bergia, Berta M

    2013-12-01

    Childhood disintegrative disorder, a rare, relentlessly progressive neurologic disorder, first described by Heller in 1908, remains a condition of great interest. It has long been debated whether it is a discrete disorder or simply a late-onset variant of childhood autism. We have studied 6 cases of childhood disintegrative disorder, collected over 8 years, and followed for 2.5 to 22 years (mean 8.6 years). Childhood disintegrative disorder begins later in life than autism, and following a period of entirely normal development; the regression is more global and more severe than in autism; seizures are more frequent than in autism, yet demonstrable organicity in childhood disintegrative disorder is decidedly rare. Lastly, the prognosis is usually much worse than in autism, but in those cases with neither seizures nor epileptiform activity on electroencephalography (EEG), the outcome may be more favorable. Childhood disintegrative disorder should be viewed as a condition distinct from childhood autism.

  12. Investigation of the performance of the disintegration test for dietary supplements.

    Science.gov (United States)

    Almukainzi, May; Salehi, Mahnor; Araci Bou-Chacra, Nadia; Löbenberg, Raimar

    2010-12-01

    The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, and . Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and one with a 1,500-mL volume. The disintegration data were analyzed using ANOVA for the following factors: beaker size, equipment (App A and B) and condition (with/without disk). Two tablet products were not sensitive to any changes in the test conditions or equipment configurations. One product was only partially sensitive to the test conditions. The other products showed impact on the disintegration time for all test conditions. The results revealed that these tablet products might pass or fail current USP disintegration requirements depending on the equipment configuration. Similar results were obtained for the two investigated capsule formulations. One product might fail current USP disintegration requirements if the large beaker was used, but might pass the disintegration requirements when the small beaker was used. Hydroxy propyl methyl cellulose capsules were mostly influenced if sodium instead of a potassium buffer was used as the immersion medium. The results demonstrate that the current harmonized ICH specifications for the disintegration test are insufficient to make the disintegration test into reliable test for dietary supplements.

  13. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

    Science.gov (United States)

    Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

    2017-01-01

    Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that

  14. Enhancement of activated sludge disintegration and dewaterability by Fenton process

    Science.gov (United States)

    Heng, G. C.; Isa, M. H.

    2016-06-01

    Municipal and industrial wastewater treatment plants produce large amounts of sludge. This excess sludge is an inevitable drawback inherent to the activated sludge process. In this study, the waste activated sludge was obtained from the campus wastewater treatment plant at Universiti Teknologi PETRONAS (UTP), Malaysia. Fenton pretreatment was optimized by using the response surface methodology (RSM) to study the effects of three operating conditions including the dosage of H2O2 (g H2O2/kg TS), the molar ratio of H2O2/Fe2+ and reaction time. The optimum operating variables to achieve MLVSS removal 65%, CST reduction 28%, sCOD 11000 mg/L and EPS 500 mg/L were: 1000 g H2O2/kg TS, H2O2/Fe2+ molar ratio 70 and reaction time 45 min. Fenton process was proved to be able to enhance the sludge disintegration and dewaterability.

  15. The role of Vatican in disintegrating of Yugoslavia

    Directory of Open Access Journals (Sweden)

    Vuković Slobodan V.

    2004-01-01

    Full Text Available Intolerance of Vatican primarily toward Serbs and afterwards towards Serbian state has long enduring history. This history got new impetus after the forming of Congregation for the religious propaganda. Vatican led policy against the forming of first Yugoslavia between the World Wars and worked on its destabilization especially after the forming of catholic organization named the Cruisers. During the II WW Vatican took full cooperation with Ustashi’s Independent State of Croatia. During this period Catholic church headed by the Holy Chair approved mass introduction into Catholicism of Serbs and their mass killing that became real genocide in scope. In last crisis during the nineties Vatican gave full help in disintegration of Yugoslavia in order to make easier proselytism on the East.

  16. The role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Wegener, Gregers; Brink, Christiaan

    not affect swimming or climbing. Lastly, locomotor activity was unaltered by all treatment conditions. Conclusions These results confirm cholinergic-cGMP-PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces...... the antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, a downstream effector for cGMP, and whether this may target known pathways in antidepressant action. Purpose We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br.......c.v.) ± atropine (1 mg/kg, i.p.), Rp-8-Br-PET-cGMP or atropine. Antidepressant-like activity was scored in terms of a reduction of immobility (in seconds) relative to vehicle-treated controls. Swimming and climbing behaviours were scored as an indication of serotonergic and noradrenergic mechanisms, respectively...

  17. Correlations between increased erection hardness and improvements in emotional well-being and satisfaction outcomes in men treated with sildenafil citrate for erectile dysfunction.

    Science.gov (United States)

    King, R; Juenemann, K-P; Levinson, I P; Stecher, V J; Creanga, D L

    2007-01-01

    To explore relationships between erection hardness and other outcomes in men with erectile dysfunction (ED). Pooled analyses were conducted on 27 randomized, double-blind, placebo-controlled trials and six open-label trials from the worldwide sildenafil database. Outcomes included erection hardness graded subjectively, hardness and sexual satisfaction questions from the International Index of Erectile Function, general and sexually-specific emotional well-being from the self-esteem and relationship questionnaire, and the erectile dysfunction inventory of treatment satisfaction. Hardness outcomes improved (with a possible dose-response relationship for the achievement of fully hard and rigid erections) and correlated positively with the other outcomes. Sildenafil 100 mg produced optimal erection hardness (fully hard and rigid erections) in a substantial proportion of men with ED. Because optimal erection hardness correlated positively with some emotional well-being and satisfaction outcomes, sildenafil 100 mg may be the most appropriate dosage for treatment of ED for most men.

  18. A randomised, double-blind, placebo-controlled trial of nightly sildenafil citrate to preserve erectile function after radiation treatment for prostate cancer

    International Nuclear Information System (INIS)

    Ilic, Dragan; Hindson, Ben; Duchesne, Gillian; Millar, Jeremy L.

    2013-01-01

    Erectile dysfunction (ED) is a common adverse event associated with treatment for prostate cancer. This study aimed to identify whether early, regular use of sildenafil after radiation treatment for prostate cancer is effective at reducing the rate of ED at 2 years. A randomised controlled trial with 27 men planned for radiation treatment for localised prostate cancer recruited from a single radiotherapy centre in Australia. Men were randomised to receive daily sildenafil, or a placebo tablet, for 6 months. The primary end-point was erectile function, as measured by the International Index of Erectile Function (IIEF) score, at 2-year follow-up. The abridged IIEF-5 survey was also used during the treatment period, and could be derived from the full IIEF at other time-points. Two-sided Student's t-tests and Mann–Whitney U-tests were used for the analysis of continuous outcomes, with Fisher's exact test for dichotomous outcomes. No difference was seen at 2 years in the primary end-point, and IIEF scores did not differ significantly between groups during the study. Men in the sildenafil group exhibited significantly better IIEF-5 scores at 4 weeks (P=0.02) and 6 months (P=0.02). There was no difference in erectile function scores between the two groups throughout the treatment period. No significant difference in adverse events was identified between the two groups. There was no evidence from this trial that sildenafil provides long-term erectile function for patients while on medication. Regular use of sildenafil may improve short-term sexual function for patients while on medication. Larger trials are required to examine the effectiveness of implementing sildenafil for prostate cancer patients undergoing radiation treatment.

  19. Colorimetric determination of sildenafil citrate (Viagra) through ion-associate complex formation.

    Science.gov (United States)

    Amin, Alaa S; Moustafa, Moustafa E; El-Dosoky, Reham

    2009-01-01

    A simple, quick, accurate, and sensitive colorimetric method is described for the determination of sildenafil citrate (SLD). The method is based on the reaction of SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate complex species; the colored products are quantitated colorimetrically at 523, 554, and 569 nm, respectively. The various experimental conditions were optimized. The stoichiometric ratio was found to be 1:1 for all ion associates; the calculated logarithmic stability constants were 8.51, 7.79, and 5.58, respectively. Beer's law was obeyed over the concentration range of 0.2-7.0 microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL. Values for molar absorptivity, Sandell sensitivity, and detection and quantification limits were also calculated. The proposed method was successfully applied to the determination of SLD in Viagra tablets and in serum samples by using the technique of standard additions with mean accuracy values of 100.06 +/- 1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60, 99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

  20. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice

    Directory of Open Access Journals (Sweden)

    Antje Bruckbauer

    2016-01-01

    Full Text Available Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.

  1. Comparative study on novel test systems to determine disintegration time of orodispersible films.

    Science.gov (United States)

    Preis, Maren; Gronkowsky, Dorothee; Grytzan, Dominik; Breitkreutz, Jörg

    2014-08-01

    Orodispersible films (ODFs) are a promising innovative dosage form enabling drug administration without the need for water and minimizing danger of aspiration due to their fast disintegration in small amounts of liquid. This study focuses on the development of a disintegration test system for ODFs. Two systems were developed and investigated: one provides an electronic end-point, and the other shows a transferable setup of the existing disintegration tester for orodispersible tablets. Different ODF preparations were investigated to determine the suitability of the disintegration test systems. The use of different test media and the impact of different storage conditions of ODFs on their disintegration time were additionally investigated. The experiments showed acceptable reproducibility (low deviations within sample replicates due to a clear determination of the measurement end-point). High temperatures and high humidity affected some of the investigated ODFs, resulting in higher disintegration time or even no disintegration within the tested time period. The methods provided clear end-point detection and were applicable for different types of ODFs. By the modification of a conventional test system to enable application for films, a standard method could be presented to ensure uniformity in current quality control settings. © 2014 Royal Pharmaceutical Society.

  2. Composition, disintegrative properties, and labeling compliance of commercially available taurine and carnitine dietary products.

    Science.gov (United States)

    Bragg, Rebecca R; Freeman, Lisa M; Fascetti, Andrea J; Yu, Zengshou

    2009-01-15

    To test the quality, disintegration properties, and compliance with labeling regulations for representative commercially available taurine and carnitine dietary products. Evaluation study. 11 commercially available taurine and 10 commercially available carnitine products. For each product, the amount of taurine or carnitine was determined and compared with the label claim. All products were evaluated for concentrations of mercury, arsenic, and selenium. Disintegration properties of 5 taurine and 8 carnitine products were determined in vitro. Labels were evaluated for compliance with FDA guidelines. 10 of 11 taurine and 10 of 10 carnitine products were within 10% of the stated label claim. Three of 11 taurine and 6 of 10 carnitine products were within 5% of the stated label claim. The median percentage difference between laboratory analysis and label claim was -5.7% (range, -26.3% to 2.5%) for taurine and 3.6% (range, -2.6% to 8.8%) for carnitine. No substantial amount of contamination with mercury, arsenic, or selenium was found in any of the products. During disintegration testing, 1 of 5 taurine products and 5 of 8 carnitine products did not disintegrate within 45 minutes during at least 1 test. Disintegration time for those that did disintegrate ranged from 1.7 to 37.0 minutes. All product labels conformed with FDA regulations. Taurine and carnitine products evaluated in this study closely adhered to manufacturer claims and labeling guidelines. However, disintegration testing suggested high variability in some products, possibly limiting uptake and use by animals that receive them.

  3. Investigation of the Performance of the Disintegration Test for Dietary Supplements

    OpenAIRE

    Almukainzi, May; Salehi, Mahnor; Araci Bou-Chacra, Nadia; Löbenberg, Raimar

    2010-01-01

    The aim of this study was to investigate how beaker size, basket assembly, use of disk, and immersion medium impact the disintegration time of dietary supplements. The disintegration times were determined for five tablet and two capsule products. A two-station disintegration tester was used with Apparatus A or Apparatus B as described in the United States Pharmacopeia (USP) chapters, and . Two beakers complying with the harmonized specifications were used, one with a volume of 1,000 mL and o...

  4. The mechanism of total disintegration of heavy nuclei by fast hadrons and nuclei

    International Nuclear Information System (INIS)

    Strugalska-Gola, E.; Strugalski, Z.

    1997-01-01

    The mechanism of the total disintegration of atomic nuclei by fast hadrons and nuclei is considered. The passage of energetic hadrons through layers of intranuclear matter, accompanied by emission of fast nucleons with kinetic energies from about 20 up to about 500 MeV from definite local small regions in the nuclei around projectile courses in them, allows one to explain simply the occurrence of the total destruction of nuclei involved in the collisions. Light nuclei may be totally disintegrated by fast hadrons and nuclei; heavier nuclei may be totally disintegrated only in central collisions of nuclei with similar mass numbers

  5. Simulation of activational grinding for rhombic sulfur particles in a disintegrator (pinned disc mill

    Directory of Open Access Journals (Sweden)

    Farit Urakaev

    2016-12-01

    Full Text Available Based on the theoretical studies, complete picture of a mechanical processing of sulfur in the disintegrator is given. Kinematic and dynamic characteristics of elastic and inelastic collisions of particles of processed rhombic sulfur with rows of disintegrator fingers are calculated. Based on the analysis of the obtained dependency of the rotation frequency of the rotors offers, advices on selecting optimal conditions for activation milling of α-sulfur in the disintegrator are given. These results can be partially used in the processing of sulfur and in other types of shock grinding devices, in particular, jet mills.

  6. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

    Directory of Open Access Journals (Sweden)

    Silvina G. Castro

    2013-01-01

    Full Text Available The main objectives of this study were (a to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form.

  7. Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

    Directory of Open Access Journals (Sweden)

    F.E. Silvera

    2011-08-01

    Full Text Available Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica aged 12 to 72 h (1660 ± 192 g received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT. Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

  8. Impact of erectile dysfunction on confidence, self-esteem and relationship satisfaction after 9 months of sildenafil citrate treatment.

    Science.gov (United States)

    Althof, Stanley E; O'Leary, Michael P; Cappelleri, Joseph C; Crowley, Arthur R; Tseng, Li-Jung; Collins, Suzanne

    2006-11-01

    The first double-blind, placebo controlled trial in the United States of the Self-Esteem And Relationship questionnaire revealed that treatment with sildenafil citrate improves erectile function and measures of quality of life in men with erectile dysfunction. We investigated long-term improvement, and correlations between improved erectile function and confidence, self-esteem and sexual relationship satisfaction in men with erectile dysfunction. This was a 36-week open label extension of the double-blind, placebo controlled trial. The blind was not broken. Patients were 18 years or older with clinically diagnosed erectile dysfunction. Erectile function was assessed using the International Index of Erectile Function. Self-esteem, confidence and relationship satisfaction were assessed using the Self-Esteem And Relationship questionnaire. Correlations were determined using Pearson's product moment coefficients. A total of 204 participants were enrolled in the open label extension, including 108 on placebo and 96 on sildenafil. In men who received placebo in the double-blind, placebo controlled phase mean erectile function scores and self-esteem, confidence and relationship satisfaction scores were increased significantly at week 36 of the open label extension (p self-esteem, confidence and relationship satisfaction were strong and positive (p self-esteem, confidence and relationship satisfaction. Following an initial 12 weeks of double-blind, placebo controlled sildenafil therapy for erectile dysfunction improvements were sustained an additional 9 months. Positive correlations between erectile function, and self-esteem, confidence and relationship satisfaction suggest that improved erectile quality can improve long-term psychosocial quality of life.

  9. Antidepressant-like properties of sildenafil in a genetic rat model of depression: Role of cholinergic cGMP-interactions

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Brink, Christiaan; Brand, Linda

    2008-01-01

    Background: The N-methyl-D-aspartate (NMDA)/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway has been implicated in the neurobiology of depression. Recently we suggested a possible complex interaction between the cholinergic and NO-cGMP pathways in the antidepressant-like response....... Conclusions: Using a genetic animal model of depression, we have confirmed the antidepressant-like property of sildenafil following “unmasking” by concomitant block of muscarinic receptors. These findings hint at a novel interaction between the cGMP and cholinergic systems in depression, and suggest...

  10. A laboratory scale model of abrupt ice-shelf disintegration

    Science.gov (United States)

    Macayeal, D. R.; Boghosian, A.; Styron, D. D.; Burton, J. C.; Amundson, J. M.; Cathles, L. M.; Abbot, D. S.

    2010-12-01

    An important mode of Earth’s disappearing cryosphere is the abrupt disintegration of ice shelves along the Peninsula of Antarctica. This disintegration process may be triggered by climate change, however the work needed to produce the spectacular, explosive results witnessed with the Larsen B and Wilkins ice-shelf events of the last decade comes from the large potential energy release associated with iceberg capsize and fragmentation. To gain further insight into the underlying exchanges of energy involved in massed iceberg movements, we have constructed a laboratory-scale model designed to explore the physical and hydrodynamic interactions between icebergs in a confined channel of water. The experimental apparatus consists of a 2-meter water tank that is 30 cm wide. Within the tank, we introduce fresh water and approximately 20-100 rectangular plastic ‘icebergs’ having the appropriate density contrast with water to mimic ice. The blocks are initially deployed in a tight pack, with all blocks arranged in a manner to represent the initial state of an integrated ice shelf or ice tongue. The system is allowed to evolve through time under the driving forces associated with iceberg hydrodynamics. Digitized videography is used to quantify how the system of plastic icebergs evolves between states of quiescence to states of mobilization. Initial experiments show that, after a single ‘agitator’ iceberg begins to capsize, an ‘avalanche’ of capsizing icebergs ensues which drives horizontal expansion of the massed icebergs across the water surface, and which stimulates other icebergs to capsize. A surprise initially evident in the experiments is the fact that the kinetic energy of the expanding mass of icebergs is only a small fraction of the net potential energy released by the rearrangement of mass via capsize. Approximately 85 - 90 % of the energy released by the system goes into water motion modes, including a pervasive, easily observed seich mode of the tank

  11. Development of novel fast-disintegrating tablets by direct compression using sucrose stearic acid ester as a disintegration-accelerating agent.

    Science.gov (United States)

    Koseki, Takuma; Onishi, Hiraku; Takahashi, Yuri; Uchida, Minoru; Machida, Yoshiharu

    2008-10-01

    It was attempted to produce novel furosemide (FS) fast-disintegrating tablets by direct compression. The combination of FS, microcrystalline cellulose, croscarmellose sodium and xylitol was used as the basic formulation, and sucrose stearic acid ester (SSE) was chosen as an additional additive. The tablets with SSE were prepared by the simple addition of SSE, using a lyophilized mixture of FS and SSE or using a FS/SSE mixture obtained by evaporation of their ethanol solution. Only the tablets, produced using the FS/SSE mixture obtained by organic solvent (ethanol) evaporation, showed hardness of more than 30 N and a disintegration time of less than 20 s, which were the properties suitable for fast-disintegrating tablets. These properties were considered to result from well-mixed and fine-powdered SSE and FS.

  12. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  13. Atrazine in sub-acute exposure results in sperm DNA disintegrity and nuclear immaturity in rats

    Directory of Open Access Journals (Sweden)

    Rajab-Ali Sadrkhanloo

    2012-03-01

    Full Text Available This study was designed to evaluate the detrimental effect of atrazine (ATR on germinal epitheliums (GE cytoplasmic carbohydrate (CH and unsaturated fatty acids (UFA ratio and to clarify the effect of ATR on serum levels of FSH, LH, testosterone and inhibin-B (INH-B. The impact of ATR exposure on total antioxidant capacity (TAC, sperm DNA packing and integrity were also investigated. Seventy two Wistar rats were used. The rats in control group received vehicle and the animals in test groups received 100, 200 and 300 mg kg-1 BW of ATR orally on daily bases for 12, 24 and 48 days. In ATR-received groups the spermatogenesis cell were presented with dense reactive sites for lipidophilic staining associated with faint cytoplasmic CH accumulation. Dissociated germinal epithelium, negative tubular and repopulation indexes were manifested. The serum levels of testosterone, FSH, LH and INH-B decreased by 85% after 48 days exposure to high dose of ATR. TAC was reduced in a time- and dose-dependent manner. The sperm DNA damage was marked in animals which exposed to high dose of ATR (72.50 ± 2.25% and the percentage of nuclear immature sperm increased up to 83.40 ± 0.89%. In conclusion, ATR not only induced its detrimental effect on the endocrine function of the testes and pituitary gland but also affected the cytoplasmic CH ratio and consequently leads to inadequate energy supplement in spermatogenesis cells. Therefore the imbalanced oxidative stress occurs in testicular tissue, which in turn enhances the sperm DNA disintegrity and nuclear immaturity.

  14. Use of anaerobic hydrolysis pretreatment to enhance ultrasonic disintegration of excess sludge.

    Science.gov (United States)

    Li, Xianjin; Zhu, Tong; Shen, Yang; Chai, Tianyu; Xie, Yuanhua; You, Meiyan; Wang, Youzhao

    2016-01-01

    To improve the excess sludge disintegration efficiency, reduce the sludge disintegration cost, and increase sludge biodegradability, a combined pretreatment of anaerobic hydrolysis (AH) and ultrasonic treatment (UT) was proposed for excess sludge. Results showed that AH had an advantage in dissolving flocs, modifying sludge characteristics, and reducing the difficulty of sludge disintegration, whereas UT was advantageous in damaging cell walls, releasing intracellular substances, and decomposing macromolecular material. The combined AH-UT process was an efficient method for excess sludge pretreatment. The optimized solution involved AH for 3 days, followed by UT for 10 min. After treatment, chemical oxygen demand, protein, and peptidoglycan concentrations reached 3,949.5 mg O2/L, 752.5 mg/L and 619.1 mg/L, respectively. This work has great significance for further engineering applications, namely, reducing energy consumption, increasing the sludge disintegration rate, and improving the biochemical properties of sludge.

  15. Measurement of disintegration rates of 60Co volume sources by the sum-peak method

    International Nuclear Information System (INIS)

    Kawano, Takao; Ebihara, Hiroshi

    1991-01-01

    The sum-peak method has been applied to the determination of the disintegration rates of 60 Co volume sources (1.05 x 10 4 Bq, 1.05 x 10 3 Bq and 1.05 x 10 2 Bq, in 100-ml polyethylene bottles) by using a NaI(Tl) detector of a diameter of 50 mm and a height of 50 mm. The experimental results showed that decreasing the disintegration rates resulted in enlarged underestimation in comparison with the true disintegration rates. It was presumed that the underestimations of the disintegration rates determined by the sum-peak method resulted from the overestimations of the areas under the sum peaks caused by the overlap of the area under the Compton scattering of the γ-ray (2614 keV) emitted from a naturally occurring radionuclide 208 Tl under the sum peaks. (author)

  16. A study of the disintegration of highly excited nuclei with the Vlasov-Uehling-Uhlenbeck equation

    International Nuclear Information System (INIS)

    Vinet, L.; Gregoire, C.; Schuck, P.; Remaud, B.; Sebille, F.

    1987-01-01

    The disintegration of hot and/or compressed nuclei is studied using (i) the Vlasov equation (VE) with imposed spherical symmetry, (ii) the VE in three dimensions (3D) and (iii) the VE in three dimensions supplemented by the Uehling-Uhlenbeck collision term (VUU). We find that case (ii) is slightly more unstable with respect to disintegration compared to case (i) whereas (iii) tends to make nuclei more stable. In all cases the thermal energies (15-20 MeV per nucleon) needed to totally disintegrate a nucleus seem to be higher than those found in static and hydrodynamic calculation. On the contrary, compressional energy very much helps disintegration. Some comments on the introduction of fluctuations and corresponding fragmentation are added. (orig.)

  17. Method of measuring the disintegration rate of a beta-emitting radionuclide in a liquid sample

    International Nuclear Information System (INIS)

    Horrocks, D.L.

    1980-01-01

    A novel liquid scintillation counting method of measuring the disintegration rate of a beta-emitting radionuclide is described which involves counting the sample at at least two different quench levels. (UK)

  18. Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics.

    Science.gov (United States)

    Lei, Ting; Guan, Ming; Liu, Jia; Lin, Hung-Cheng; Pfattner, Raphael; Shaw, Leo; McGuire, Allister F; Huang, Tsung-Ching; Shao, Leilai; Cheng, Kwang-Ting; Tok, Jeffrey B-H; Bao, Zhenan

    2017-05-16

    Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal-oxide-semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 μm) and ultralightweight (∼2 g/m 2 ) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics.

  19. Effect of disintegration wave grinding on fractional protein and amino acid composition of chickpea

    Directory of Open Access Journals (Sweden)

    G. O. Magomedov

    2013-01-01

    Full Text Available The study of fractional changes and amino acid composition of proteins in the application of chickpea disintegration wave grinding. Comparative analysis of six varieties of chickpea before and after grinding.

  20. Effect of disintegration wave grinding on fractional protein and amino acid composition of chickpea

    OpenAIRE

    G. O. Magomedov; M. K. Sadigova; S. I. Lukina; V. Y. Kustov

    2013-01-01

    The study of fractional changes and amino acid composition of proteins in the application of chickpea disintegration wave grinding. Comparative analysis of six varieties of chickpea before and after grinding.