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Sample records for delayed release tablets

  1. Bioavailability and stability of erythromycin delayed release tablets.

    Science.gov (United States)

    Ogwal, S; Xide, T U

    2001-12-01

    Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

  2. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data

  3. Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

    2017-02-01

    Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

  4. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2012-10-01

    Full Text Available The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0, and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets. Keywords: Aspirin delayed-release tablets, Drug dissolution test, Fiber-optic dissolution system, UV–vis spectrum

  5. Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.

    Science.gov (United States)

    Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J

    2011-04-01

    The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.

  6. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  7. Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.

    Science.gov (United States)

    Fujiki, Sadahiro; Watanabe, Narumi; Iwao, Yasunori; Noguchi, Shuji; Mizoguchi, Midori; Iwamura, Takeru; Itai, Shigeru

    2015-08-01

    The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Bioadhesive Controlled Release Clotrimazole Vaginal Tablets | Bhat ...

    African Journals Online (AJOL)

    Conclusion: This study indicates the possible use of suitable mixtures of natural and semi-synthetic cellulosic polymers for the preparation of clotrimazole mucoadhesive tablets for application as a vaginal controlled delivery system. Keywords: Clotrimazole, Swelling, Cellulosic polymers, Guar gum, Bioadhesion, Release ...

  9. DEVELOPMENT OF SUSTAINED RELEASE TABLETS ...

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... The SR dosage forms that release drugs pH independently in .... were determined; Post compression parameters such as weight variation test, hardness, ... Based on the ICH guidelines 12, the stability studies were carried out ...

  10. A New Application of Lipid Nanoemulsions as Coating Agent, Providing Zero-Order Hydrophilic Drug Release from Tablets

    Directory of Open Access Journals (Sweden)

    Nicolas Anton

    2012-01-01

    Full Text Available The objective of the present investigation was to evaluate potential of nanoemulsions as a coating material for the tablets. The nanoemulsion of size less than 100 nm was prepared using a simple and low-energy spontaneous emulsification method. Conventional tablets containing theophylline as a model hydrophilic drug were prepared. The theophylline tablets were coated with the nanoemulsion using a fluid bed coater. The effect of different levels of the nanoemulsion coating on the theophylline release was evaluated. The theophylline tablets containing different levels of the nanoemulsion coating could be successfully prepared. Interestingly, the coating of tablet with the nanoemulsion resulted in zero-order release of theophylline from the tablets. The noncoated theophylline tablets release the entire drug in less than 2 minutes, whereas nanoemulsion coating delayed the release of theophylline from tablets. This investigation establishes the proof of concept for the potential of nanoemulsions as a coating material for tablets.

  11. Preparation of venlafaxine hydrochloride sustained-release tablets

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    GUO Lingling

    2013-08-01

    Full Text Available To prepare venlafxine hydrochloride sustained-release tablets.Hydroxypropylmethyl cellulose(HPMC and methyl cellulose(MC were used as main materials to prepare sustained-release tablets of velafaxine hydrochloride and the influence of important factors on in vitro release curves of venlafaxine hydrochloride sustained-release tablets was investigated.Results:The optimal prescription included 100 mg HPMC,25 mg MC,and 2.5% glidant in one tablet prepared with 30kN.The tablets were prepared with the method of wet granulation by NO.16 mesh sieve.The tablets exhibited good sustained-release property in phosphate buffered solution (pH=6.8.The as-prepared venlafxine hydrochloride sustained-release tablets have good sustained-release property.

  12. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    Purpose: To formulate extended-release tablets of diclofenac sodium based on ispaghula husk. Methods: Tablets with varying proportions of diclofenac sodium and ispaghula husk were formulated by wet granulation technique at a fixed compression force of 10 kN. The formulated tablets were evaluated for ...

  13. [Influence of polymer type on the physical properties and the release study of papaverine hydrochloride from tablets].

    Science.gov (United States)

    Kasperek, Regina; Polski, Andrzej; Sobótka-Polska, Karolina; Poleszak, Ewa

    2014-01-01

    Polymers are widely used in drug manufacturing. Researchers studied their impact on the bioavailability of active substances or on physical properties of tablets for many years. To study the influence of polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH 102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release profile of papaverine hydrochloride from tablets and on the physical properties of tablets. Six series of uncoated tablets were prepared by indirect method, with previous wet granulation. Tablets contained papaverine hydrochloride and various excipients. The physical properties of the prepared granules, tablets and the release profile of papaverine hydrochloride from tablets were examined. The content of papaverine hydrochloride from the release study were determined spectrophotometrically. All tablets met the pharmacopoeia requirements during following tests: the disintegration time of tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose formulations, their dimensions, the resistance to crushing of tablets and the drug substance content in the tablet. In four cases more than 80% of papaverine was released up to 2 min, in one formula it was up to 5 min, and in last one up to 10 min. Tablets containing crospovidone disintegrated faster than tablets with croscarmellose sodium. Adding gelatinized starch to the tablet composition increased the disintegration time, hardness and delayed the release of papaverine. During the wet granulation process, granules containing polyvinylpyrrolidone were characterized by a suitable flow properties and slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared to tablets with Avicel PH 101 had less weight loss during the test of mechanical resistance, improved hardness and faster release profile of papaverine from tablets.

  14. The influence of granulating solvents on drug release from tablets ...

    African Journals Online (AJOL)

    ... significantly lower than the other wet granulated tablets, but higher than the matrix tablets. The granulating solvent influenced the release of drug which increased with increase in the water content. Key Words: Grewia gum: Granulating solvents; Release mechanisms. Journal of Pharmacy and Bioresources Vol.1(1) 2004: ...

  15. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends. A Moin, H.G Shivakumar. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose ...

  16. RELEASE AND MUCOADHESION PROPERTIES OF DICLOFENAC MATRIX TABLETS FROM NATURAL AND SYNTHETIC POLYMER BLENDS.

    Science.gov (United States)

    Odeniyi, Michael A; Khan, Nasir H; Peh, Kok K

    2015-01-01

    The delayed release and mucoadhesive properties of Cedrela gum and hydroxypropylmethylcellulose blend in diclofenac sodium tablet formulations were evaluated. Tablets were prepared by direct compression and the crushing strength and detachment force were found to increase from 74.49 ± 1.22 to 147.25 ± 2.57 N and 0.302 ± 0.36 to 1.141 ± 0.05 N from low to high level of polymers, respectively. The release kinetics followed Korsmeyer-Peppas release and the n varied between 0.834 and 1.273, indicating that the release mechanism shifts from Fickian to super case I (anomalous release). The drug release profile fits a pulsatile-release pattern characterized by a lag time followed by a more or less rapid and complete drug release. The Cedrela gum-hydroxypropylmethylcelluse blend tablets delayed diclofenac release for 2 h and sustained the release for 12 h. The polymer blend delayed drug release in the 0.1 M HCl simulating gastric environment and subsequent release pH 6.8 phosphate buffer.

  17. Validation and Application of a New Reversed Phase HPLC Method for In Vitro Dissolution Studies of Rabeprazole Sodium in Delayed-Release Tablets

    Directory of Open Access Journals (Sweden)

    Md. Saddam Nawaz

    2013-01-01

    Full Text Available The purpose of this study was to develop and validate a new reversed phase high performance liquid chromatographic (RP-HPLC method to quantify in vitro dissolution assay of rabeprazole sodium in pharmaceutical tablet dosage form. Method development was performed on C 18, 100×4.6 mm ID, and 10 μm particle size column, and injection volume was 20 μL using a diode array detector (DAD to monitor the detection at 280 nm. The mobile phase consisted of buffer: acetonitrile at a ratio of 60 : 40 (v/v, and the flow rate was maintained at 1.0 mL/min. The method was validated in terms of suitability, linearity, specificity, accuracy, precision, stability, and sensitivity. Linearity was observed over the range of concentration 0.05–12.0 μg/mL, and the correlation coefficient was found excellent >0.999. The method was specific with respect to rabeprazole sodium, and the peak purity was found 99.99%. The method was precise and had relative standard deviations (RSD less than 2%. Accuracy was found in the range of 99.9 to 101.9%. The method was robust in different variable conditions and reproducible. This proposed fast, reliable, cost-effective method can be used as quality control tool for the estimation of rabeprazole sodium in routine dissolution test analysis.

  18. Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

    Science.gov (United States)

    Tolia, Gaurav; Li, S Kevin

    2012-11-01

    Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. ... therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ..... is simple to adopt and cost-effective. In this ...

  20. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

    Science.gov (United States)

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of

  1. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    1Vels College of Pharmacy, Pallavaram, Chennai, India, 2Jeffrey Cheah School of Medicine and Health Sciences, Monash University, ... Keywords: Ispaghula husk, Extended release tablet, Diclofenac sodium, Release kinetics. .... release, i.e., Qt vs t, log (Q0-Qt) vs t and Qt vs .... Wallis TE, Textbook of Pharmacognosy, CBS.

  2. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Crushed tablets: does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

    Science.gov (United States)

    Manrique, Yady J; Lee, Danielle J; Islam, Faiza; Nissen, Lisa M; Cichero, Julie A Y; Stokes, Jason R; Steadman, Kathryn J

    2014-01-01

    To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their

  4. Design and evaluation of nicorandil extended-release tablet

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  5. Application of a Biodegradable Polyesteramide Derived from L-Alanine as Novel Excipient for Controlled Release Matrix Tablets.

    Science.gov (United States)

    Bonillo Martínez, Ana Dora; Galán, Inés Carmen Rodríguez; Bellver, María Victoria Margarit

    2017-11-01

    This pre-formulation study assays the capacity of the polyesteramide PADAS, poly (L-alanine-dodecanediol-L-alanine-sebacic), as an insoluble tablet excipient matrix for prolonged drug release. The flow properties of PADAS were suitable for tableting, and the compressibility of tablets containing exclusively PADAS was evaluated by ESEM observation of the microstructure. The tablets were resistant to crushing and non-friable and they did not undergo disintegration (typical features of an inert matrix). Tablets containing 33.33% sodium diclofenac (DF), ketoprofen (K) or dexketoprofen trometamol (DK-T) as a model drug, in addition with 66.67% of polymer, were formulated, and the absence of interactions between the components was confirmed by differential scanning calorimetry. Dissolution tests showed that PADAS retained DF and K and prolonged drug release, following a Higuchi kinetic. The tablets containing DK-T did not retain the drug sufficiently for prolonged release to be established. Tablets containing DK-T and 66.67, 83.33 or 91.67% PADAS, compressed at 44.48 or 88.96 kN, were elaborated to determine the influence of the polymer amount and of the compression force on DK-T release. Both parameters significantly delayed drug release, except when the proportion of polymer was 91.67%.

  6. Mechanochemical effect on swelling and drug release of natural polymer matrix tablets by X-ray computed tomography.

    Science.gov (United States)

    Hattori, Yusuke; Takaku, Tomomi; Otsuka, Makoto

    2018-03-25

    The relationships between the physicochemical properties of milled starch and drug release from tablets were investigated quantitatively using a drug release kinetic method and X-ray computed tomography (XCT). The samples were prepared from raw β-starch by milling in a planetary ball mill. The tablets, containing 5% theophylline (TH), 94% milled starch, and 1% magnesium stearate, were compressed at 6 kN. The drug-release and gel-forming processes were measured simultaneously using an original dissolution tester with an XCT instrument. Drug release from the tablet was delayed with increasing milling time, because the TH tablet formed a typical gel-layer on the outside of the tablet. The relationship between the crystallinity of milled starch and mean drug release time (MDT) for the TH tablets showed almost a straight inverse proportional relationship. The plots of MDT against area under the curve of the swelling ratio profiles of the TH tablets had a good straight line. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

    African Journals Online (AJOL)

    Microcrystalline cellulose (Avicel PH 101), starch (Sta-Rx 1500) and lactose monohydrate were used as diluents in the formulations while the effect of sodium lauryl sulphate (wetting agent) was studied for some of the formulations. The tablets were characterized for carvedilol phosphate release in both simulated gastric and ...

  8. Printing Tablets with Fully Customizable Release Profiles for Personalized Medicine.

    Science.gov (United States)

    Sun, Yajuan; Soh, Siowling

    2015-12-16

    Personalizing the release profiles of drugs is important for different people with different medical and biological conditions. A technically simple and low-cost method to fabricate fully customizable tablets that can deliver drugs with any type of release profile is described. The customization is intuitively straightforward: the desired profile can simply be "drawn" and printed by a 3D printer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  10. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  11. 78 FR 66009 - Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not...

    Science.gov (United States)

    2013-11-04

    ...] Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that INVEGA (paliperidone) extended-release tablet...-release tablet, 12 mg, if all other legal and regulatory requirements are met. FOR FURTHER INFORMATION...

  12. Impairment of the in vitro Release of Carbamazepine from Tablets

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

    Full Text Available Carbamazepine belongs to the class II biopharmaceutical classification system (BCS which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. The present study deals with the formulations of immediate release tablets of poorly soluble carbamazepine. As model tablets for this investigation, two formulations (named “A” and “B” formulations of carbamazepine tablets labeled to contain 200 mg were evaluated. The aim of this study was to establish possible differences in dissolution profile of these two formulations purchased from the local market.The increased crystallinity together with enlarged particle size, enhanced aggregation and decreased wettability of the drug, resulted in insufficient dissolution rate for formulation “B’.’ From the dissolution point of view, this formulation was inferior to the formulation “A, due to the solubilization effect.

  13. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    Science.gov (United States)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  14. Investigation of delayed fission gas release

    International Nuclear Information System (INIS)

    Cayet, Nicolas

    1996-05-01

    The study of the fission gas release process in the high burnup rig IFA-562 has revealed a particular fuel behaviour: a delay in the fission gas release process. It appeared that an important release of gas was measured by the pressure transducers once the power had decreased, whereas, during steady-state operation, the pressure did not increase very much. After examinations, the gap size has been concluded to be the main parameter involving this delay. However the burnup could have been a potential factor, its role is mainly to close the gap by swelling. The observations of low burnup rods have shown the same delayed fission gas release, the gap being small by design and closed essentially by thermal expansion. The study of the kinetics has demonstrated the time-independency of the phenomenon. Thus the proposed mechanism driving this delayed fission gas release would involve three consecutives stages. During steady-state, the gas is released into the interlinkage network of grain boundary bubbles and cracks. Due to the closed gap, the gas is trapped in some void volumes, unable to escape the pellet. During power reduction, the gap and some old/new cracks open, immediately providing a path for the gas to the pressure transducers and explaining this delay in the fission gas release. (author)

  15. Plasticisation of amylodextrin by moisture : Consequences for drug release from tablets

    NARCIS (Netherlands)

    Steendam, Rob; Eissens, Anco C.E.; Frijlink, Henderik W.; Lerk, Coenraad F.

    2000-01-01

    Moisture influences the consolidation behaviour of amylodextrin powders and the porosity and mechanical strength of compacts thereof. The aim of this study is to relate moisture content and compact properties to drug release characteristics of amylodextrin tablets. Therefore, amylodextrin tablets

  16. Design and characterization of controlled release tablet of metoprolol

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2012-01-01

    Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

  17. Formulation of Dipyridamole Sustained Release Tablet Using Floating System

    Directory of Open Access Journals (Sweden)

    Lenny Mauilida Valentina

    2011-06-01

    Full Text Available Dipyridamole is a drug for prevention of postoperative thromboembolic complication of heart valve replacement and long term therapy of angina pectoris will be well absorbed in stomach. To maintain therapeutic plasma concentration in long time and to increase bioavalaibility is needed a sustained release dosage form having the long residence time in the stomach. The objective of this research was to make floating sustained release tablet of dipyridamole conforming to the requirement that was set up by dipyridamol therapeutic concentration. Tablets were made by wet granulation method using aquadest as a liquid binder, HPMC K4M, Ac-di-sol, Avicel PH 102, talk, and Mg stearat. Dissolution assay was carried out using type 2 release tester at rotation speed of 50 rpm in medium 900 mL HCl 0.1 N at 37 ± 0.5 °C for 8 hours. The formulation containing of 50 mg dipirydamole, HPMC K4M (30%, Ac-di-sol (20%, Avicel PH 102 (37%, talk (2%, and Mg stearat (1% released 59.61 ± 6.73% and 89.34 ± 5.87% of dipyridamole respectively after 4 and 8 hours that conformed to the requirement.

  18. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    Directory of Open Access Journals (Sweden)

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  19. In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

    Science.gov (United States)

    Pignatello, R; Consoli, P; Puglisi, G

    2000-01-01

    In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

  20. Design and evaluation of lornoxicam bilayered tablets for biphasic release

    Directory of Open Access Journals (Sweden)

    Songa Ambedkar Sunil

    2012-12-01

    Full Text Available The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC and polyethylene oxide (PEO to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p O objetivo do presente trabalho foi desenvolver comprimidos bicamada de lornoxicam para atingir padrão de liberação bifásica. Preparou-se, por compressão direta, comprimido bicamada, consistindo de uma camada de liberação imediata e uma de liberação controlada. A liberação controlada foi obtida pelo uso de vários polímeros naturais hidrofílicos, semi-sintéticos e sintéticos, tais como goma xantana, hidroxipropilmetil celulose (HPMC e óxido de polietileno (PEO para modular a liberação do fármaco. Os perfis de liberação in vitro mostraram comportamento bifásico em que a camada de liberação imediata (IR contendo lornoxicam foi liberada em 15 minutos, enquanto a camada de liberação controlada (CR liberou o fármaco em mais de 24 horas, Todos os comprimidos bicamada

  1. Compressional, mechanical and release properties of a novel gum in paracetamol tablet formulations

    Directory of Open Access Journals (Sweden)

    Adedokun Musiliu O.

    2014-09-01

    Full Text Available The binding properties of Eucalyptus gum obtained from the incised trunk of Eucalyptus tereticornis, were evaluated in paracetamol tablet formulations, in comparison with that of Gelatin B.P. In so doing, the compression properties were analyzed using density measurements and the compression equations of Heckel, Kawakita and Gurham. In our work, the mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets, while the drug release properties of the tablets were assessed using disintegration and dissolution times. The results of the study reveal that tablet formulations incorporating Eucalyptus gum as binder, exhibited faster onset and higher amount of plastic deformation during compression than those containing gelatin. What is more, the Gurnham equation could be used as a substitute for the Kawakita equation in describing the compression properties of pharmaceutical tablets. Furthermore, the crushing strength, disintegration and dissolution times of the tablets increased with binder concentration, while friability values decreased. We noted that no significant differences in properties exist between formulations derived from the two binders (p > 0.05 exist. While tablets incorporating gelatin exhibited higher values for mechanical properties, Eucalyptus gum tablets had better balance between mechanical and release properties - as seen from the CSFR/Dt values. Tablets of good mechanical and release properties were prepared using Eucalyptus gum as a binder, and, therefore, it could serve as an alternative binder in producing tablets with good mechanical strength and fast drug release.

  2. Influence of Natural, Synthetic Polymers and Fillers on sustained release matrix tablets of Pregabalin

    OpenAIRE

    Vijaya Durga. K; Ashok Kumar. P; Suresh V Kulkarni

    2013-01-01

    The objective of the present study was to develop sustained release matrix tablets of Pregabalin for the treatment of neuropathic pain and epilepsy. The tablets were prepared by wet granulation and formulated using drug with Hydrophilic, hydrophobic, synthetic, natural polymers and 4 different fillers were used. The effect of Polymer concentration, combination and fillers on drug release rate was analyzed for the formulations F-1 to F-17. The tablets were subjected to physicochemical studies,...

  3. Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

    Science.gov (United States)

    Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B

    2010-12-01

    Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

  4. 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.

  5. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  6. Fabrication of ketoprofen controlled-release tablets using biopolymeric hydrophilic matrices: in-vitro studies

    International Nuclear Information System (INIS)

    Rashid, S.; Khan, B.A.; Khan, G.M.

    2017-01-01

    Ketoprofen is propionic acid derivative and belongs to the Non-Steroidal anti-inflammatory group of drugs. Due to the short half-life, dosage frequency, patient non-compliance and side effects such as gastrointestinal disturbance, peptic ulceration and gastro intest inal bleeding, it is considered to be good candidate for formulation into controlled release dosage forms. Directly compressed controlled released ( CR) tablets using Acrylic acid derivatives were prepared and evaluated. In-Vitro Physicochemical assessment of the formulated tablets were performed using different physicochemical, dimensional and quality control tests such as weight variation, thickness and diameter, hardness test, friability test, content uniformity, disintegration and dissolution testing. Results of all these tests were formed within acceptable range. The effect of carbomer polymers on the tablet characteristics, drug release rates, release patterns and release kinetics were investigated. The F2-metric technique was applied to compare dissolution profiles of ketoprofen and carbopol tablets with ketoprofen SR - tablets taken as standard preparation. Acrylic acid derivatives when used as polymers resulted in an extended release profile of about 12 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the tablets was found to be an anomalous type involving diffusion and erosion. Controlled- release Ketoprofen tablets appear to be a good choice for the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Convenient once-daily administration may help improve patient's compliance. (author)

  7. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

    Science.gov (United States)

    Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

    2012-05-30

    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent

  9. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  10. Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

    Science.gov (United States)

    Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

    2011-10-09

    Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Hui Ming Chua

    2016-01-01

    Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

  12. Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

    Science.gov (United States)

    Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

    2012-01-01

    We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

  13. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets.

    Science.gov (United States)

    Zhang, Jiaxiang; Feng, Xin; Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2017-03-15

    The main objective of this work was to explore the potential of coupling fused deposition modeling in three-dimensional (3D) printing with hot-melt extrusion (HME) technology to facilitate additive manufacturing, in order to fabricate tablets with enhanced extended release properties. Acetaminophen was used as the model drug and different grades and ratios of polymers were used to formulate tablets. Three-point bending and hardness tests were performed to determine the mechanical properties of the filaments and tablets. 3D-printed tablets, directly compressed mill-extruded tablets, and tablets prepared from a physical mixture were evaluated for drug release rates using a USP-II dissolution apparatus. The surface and cross-sectional morphology of the 3D-printed tablets were assessed by scanning electron microscopy. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the crystal states and thermal properties of materials, respectively. The 3D-printed tablets had smooth surfaces and tight structures; therefore, they showed better extended drug release rates than the directly compressed tablets did. Further, this study clearly demonstrated the feasibility of coupling HME with 3D printing technology, which allows for the formulation of drug delivery systems using different grades and ratios of pharmaceutical polymers. In addition, formulations can be made based on the personal needs of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    Science.gov (United States)

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-05

    Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

  15. Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

    Science.gov (United States)

    Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

    2017-03-01

    Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

  16. The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets

    NARCIS (Netherlands)

    Van Veen, B.; Pajander, J.; Zuurman, K.; Lappalainen, R.; Poso, A.; Frijlink, H.W.; Ketolainen, J.

    2005-01-01

    This study investigates the release mechanism of a hydrophilic drug (caffeine) from hydrophobic matrix tablets composed of starch acetate. Different particle size fractions of starch acetate were mixed with caffeine (22% V/V) to obtain various mixture organisations in the powder, as 14 well as in

  17. The application of povidone in the preparation of modified release tablets

    Directory of Open Access Journals (Sweden)

    Kasperek Regina

    2016-06-01

    Full Text Available The aim of the study was to investigate the modified release of a model substance, of tablets containing different types of Kollidon and particular additives. Additionally, the release kinetics and mechanism of prolonged release of certain tablet preparations were investigated. In this work, tablets containing different types of povidone (Kollidon CL, Kollidon 30, Kollidon SR and other excipients were prepared by the direct compression technique. The results showed that tablets with fast disintegration and release should contain in their composition, Kollidon CL, lactose and Avicel, however, the use of β-CD instead of lactose or Avicel brings about a slight prolongation in the disintegration time of tablets and the release of an active substance. Furthermore, while other tablet compositions generated within this study must be considered as being prolonged release types, only two of these showed the best fitted mathematical models. The in vitro dissolution data reveal that the dissolution profiles of the two formulations, one containing Kollidon SR with the addition of Kollidon 30, and the second with HPMC K15M, Kollidon 30, Kollidon CL and lactose, best fitted the Higuchi model. Moreover, the release mechanism of these two formulations plotted well into Korsmeyer-Peppas, indicating a coupling of drug diffusion in the hydrated matrix, as well as polymer relaxation – the so-called anomalous transport (non-Fickian.

  18. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing.

    Science.gov (United States)

    Goyanes, Alvaro; Fina, Fabrizio; Martorana, Annalisa; Sedough, Daniel; Gaisford, Simon; Basit, Abdul W

    2017-07-15

    The aim of this study was to manufacture 3D printed tablets (printlets) from enteric polymers by single filament fused deposition modeling (FDM) 3D printing (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from three different grades of the pharmaceutical excipient hypromellose acetate succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these filaments into enteric printlets incorporating up to 50% drug loading with two different infill percentages (20 and 100%). X-ray Micro Computed Tomography (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the core compared to 100% infill, and that the density of the 50% drug loading printlets was higher than the equivalent formulations loaded with 5% drug. In biorelevant bicarbonate dissolution media, drug release from the printlets was dependent on the polymer composition, drug loading and the internal structure of the formulations. All HPMCAS-based printlets showed delayed drug release properties, and in the intestinal conditions, drug release was faster from the printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not only to manufacture delayed release printlets without the need for an outer enteric coating, but it is also feasible to adapt the release profile in response to the personal characteristics of the patient, realizing the full potential of additive manufacturing in the development of personalised dose medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Formulation and in vivo evaluation of diclofenac sodium sustained release matrix tablet: effect of compression force.

    Science.gov (United States)

    Taha, Ehab Ibrahim; Shazly, Gamal Abdel-Ghany; Harisa, Gamaleldin Ibrahim; Barakat, Nahla Sedik; Al-Enazi, Fouza Kayem; Elbagory, Ibrahim Mostafa

    2015-03-01

    In the present study, Diclofenac Sodium (DS) matrix tablets were prepared by direct compression method under different compression forces (5, 10, 15 and 20 KN), using ethylcellulose as matrix forming material. The produced tablets were characterized on the foundation of satisfactory tablet properties such as hardness, friability, drug content, weight variations and in vitro drug release rate. Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray diffraction have been used to investigate any incompatibilities of the tablet's ingredients. Additionally, in vivo bioavailability has been investigated on beagle dogs. Data obtained revealed that, upon increasing compression force the in vitro drug release was sustained and the T(max) value was four hours (for formulations compressed at 15 and 20 kN) compared to the conventional voltarine(®) 50 tablets (T(max) value of 2 hours).

  20. Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

    Science.gov (United States)

    Emeje, Martins; Olaleye, Olajide; Isimi, Christiana; Fortunak, Joseph; Byrn, Stephen; Kunle, Olobayo; Ofoefule, Sabinus

    2010-01-01

    Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

  1. STUDIES ON NATURAL AND SYNTHETIC POLYMERS FOR CONTROLLED RELEASE MATRIX TABLET OF ACECLOFENAC

    OpenAIRE

    Abhishek S. Joshi *, Deepak A. Joshi , Avinash V. Dhobale , Sandhya S. Bundel , Vijay R. Chakote, Gunesh N. Dhembre

    2018-01-01

    The present study was aimed to design new oral controlled release matrix tablets of new NSAID Aceclofenac for once a day by using 10, 15, 20 and 25% of GG:HPMC and XG:HPMC mixture in the ratio 1:1 by wet granulation method. The prepared tablets subjected to in vitro drug release studies in pH 7.4 buffer solution. All the formulation meets the pre-compression and compression characteristics. All the tablets prepared with 10, 15, 20 and 25% of HPMC: XG mixture in the ratio 1:1 fails to meet the...

  2. CONTROLLED-RELEASE OF PARACETAMOL FROM AMYLODEXTRIN TABLETS - IN-VITRO AND IN-VIVO RESULTS

    NARCIS (Netherlands)

    VANDERVEEN, J; EISSENS, AC; LERK, CF

    Amylodextrin is a suitable excipient for the design of solid controlled-release systems. The release of paracetamol from tablets containing 30% drug and 70% amylodextrin was studied in vitro and in vivo. In vitro dissolution profiles showed almost-constant drug release rates during 8 hr, when

  3. Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

    Science.gov (United States)

    Yanfei, Miao; Guoguang, Chen; Lili, Ren; Pingkai, Ouyang

    2017-03-01

    The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged T max and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

  4. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

    Science.gov (United States)

    Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

    2011-01-01

    The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

  5. Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

    Science.gov (United States)

    Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

    2016-01-01

    The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

  6. Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets.

    Science.gov (United States)

    Huanbutta, Kampanart; Cheewatanakornkool, Kamonrak; Terada, Katsuhide; Nunthanid, Jurairat; Sriamornsak, Pornsak

    2013-08-14

    Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

    Science.gov (United States)

    Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

    2013-01-01

    A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

  8. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  9. [The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

    Science.gov (United States)

    Tomassini, L; Michailova, D; Naplatanova, D; Slavtschev, P

    1979-12-01

    The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

  10. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    MK and the formulations were also characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean dissolution time (MDT) and lower dissolution efficiency than those prepared with karaya gum.

  11. 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...

  12. 3D extrusion printing of high drug loading immediate release paracetamol tablets.

    Science.gov (United States)

    Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

    2018-03-01

    The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

    Science.gov (United States)

    Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

    2015-06-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

  14. Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets.

    Science.gov (United States)

    Zaheer, Kamran; Langguth, Peter

    2018-03-01

    Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force - time curves revealed a direct relation of maximum disintegration force (F max ) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

  15. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  16. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

    Science.gov (United States)

    Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

    2017-07-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p

  17. Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design.

    Science.gov (United States)

    Tak, Jin Wook; Gupta, Biki; Thapa, Raj Kumar; Woo, Kyu Bong; Kim, Sung Yub; Go, Toe Gyeong; Choi, Yongjoo; Choi, Ju Yeon; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-05-01

    The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1 ), ratio of HPMC to drug in the SR layer (X 2 ), and ratio of Eudragit RL PO to drug in the SR layer (X 3 ). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1 ), % drug released in pH 1.2 at 2 h (Y 2 ), and % drug released in pH 6.8 at 12 h (Y 3 ). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations.

  18. [Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

    Science.gov (United States)

    Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

    2015-01-01

    In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

  19. Polymeric materials and formulation technologies for modified-release tablet development.

    Science.gov (United States)

    Zarate, J; Igartua, M; Hernández, R M; Pedraz, J L

    2009-11-01

    Over the last years significant advances have been made in the area of drug delivery with the development of modified-release (MR) dosage forms. The present review is divided into two parts, one dealing with technologies for the design of modified-release drug delivery tablets and the other with the use of synthetic and natural polymers that are capable of controlling drug release.

  20. 3D printing of tablets containing multiple drugs with defined release profiles.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. Copyright © 2015. Published by Elsevier B.V.

  1. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  2. The effect of excipients on the release kinetics of diclofenac sodium and papaverine hydrochloride from composed tablets.

    Science.gov (United States)

    Kasperek, Regina; Trebacz, Hanna; Zimmer, Łukasz; Poleszak, Ewa

    2014-01-01

    For increased analgesic effect, new composed tablets containing diclofenac sodium (DIC) with an addition of papaverine hydrochloride (PAP) were prepared to investigate the mechanism of release of the active substances from tablets with different excipients in eight different formulations. To detect the possible interactions between active substances and excipients differential scanning calorimetry (DSC) was used. A shift of the melting point and enthalpy values of the physical mixtures of tablets components suggested a kind of interaction between components in certain formulations, however, the tabletting process was not disturbed in any of them. Kinetics of drug release from formulations was estimated by zero order, first order and Higuchi and Korsmeyer-Peppas models using results of dissolution of DIC and PAP from tablets. The study revealed that the mechanism of release of active substances was dependent on the excipients contained in tablets and the best fitted kinetics models were obtained for formulations with potentially prolonged release of DIC and PAP.

  3. In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

    African Journals Online (AJOL)

    decreased while Starch 1500 and lactose monohydrate increased drug release. Drug release mechanism ... case of antihypertensive agents to maintain constant blood levels ... systems because of their low toxicity, pH- independent swelling ...

  4. Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

    Science.gov (United States)

    Karkossa, Frank; Klein, Sandra

    2017-10-01

    The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

  5. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    Directory of Open Access Journals (Sweden)

    Fatemeh Pourhashem

    2016-06-01

    Full Text Available The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M as release retardant, polyvinyl pyrrolidone (PVP k30 as binder and Magnesium Stearate using Factorial design. In vitro release study of matrix tablets was carried out in 0.01N HCl for 2 hours. All prepared matrix tablets were evaluated for physicochemical evaluation and drug content. The formulation that had release profile according to United State Pharmacopoeia selected for stability study according to ICH guidelines.

  6. Release mechanisms of acetaminophen from polyethylene oxide/polyethylene glycol matrix tablets utilizing magnetic resonance imaging.

    Science.gov (United States)

    Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Suzuki, Masazumi; Yamanashi, Shigeyuki; Ozaki, Yukihiro; Kitamura, Satoshi

    2010-08-16

    Release mechanism of acetaminophen (AAP) from extended-release tablets of hydrogel polymer matrices containing polyethylene oxide (PEO) and polyethylene glycol (PEG) were achieved using flow-through cell with magnetic resonance imaging (MRI). The hydrogel forming abilities are observed characteristically and the layer thickness which is corresponding to the diffusion length of AAP has a good correlation with the drug release profiles. In addition, polymeric erosion contribution to AAP releasing from hydrogel matrix tablets was directly quantified using size-exclusion chromatography (SEC). The matrix erosion profile indicates that the PEG erosion kinetic depends primarily on the composition ratio of PEG to PEO. The present study has confirmed that the combination of in situ MRI and SEC should be well suited to investigate the drug release mechanisms of hydrogel matrix such as PEO/PEG. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release.

    Science.gov (United States)

    Hamed, Rania; Al Baraghthi, Tamadur; Sunoqrot, Suhair

    2016-11-21

    Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70 mg/tablet) and high (170 mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.

  8. Effect of molecular weight and glass transition on relaxation and release behaviour of poly(DL-lactic acid) tablets

    NARCIS (Netherlands)

    Steendam, R.; Van Steenbergen, M.J.; Hennink, W.E.; Frijlink, H.W.; Lerk, C.F.

    2001-01-01

    Different molecular weight grades of poly(DL-lactic acid) were applied as release controlling excipients in tablets for oral drug administration. The role of molecular weight and glass transition in the mechanism of water-induced volume expansion and drug release of PDLA tablets was investigated.

  9. Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

    Directory of Open Access Journals (Sweden)

    Shahid Sarwar

    2012-12-01

    Full Text Available The present study was undertaken to develop sustained release (SR matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R² values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (PO presente estudo foi realizado para desenvolver (SR matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e

  10. Swelling kinetics of spray-dried chitosan acetate assessed by magnetic resonance imaging and their relation to drug release kinetics of chitosan matrix tablets.

    Science.gov (United States)

    Huanbutta, Kampanart; Sriamornsak, Pornsak; Limmatvapirat, Sontaya; Luangtana-anan, Manee; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Nunthanid, Jurairat

    2011-02-01

    Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1N HCl, pH 6.8 and pH 5.0 Tris-HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris-HCl, was also studied. In 0.1N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris-HCl buffers are Fickian diffusion according to their best fit to Higuchi's model as well as the drug release kinetics in all the media. The high swelling rate (k(s)(')) was found to delay the drug release rate (k'). The linear relationship between the swelling and fractions of drug release in Tris-HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris-HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

    Directory of Open Access Journals (Sweden)

    Gurpreet Arora

    2011-01-01

    Full Text Available The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w. The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm 2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4. Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4 with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

  12. 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.

  13. The effect of hydrophilic and hydrophobic polymers on release profiles of diclofenac sodium from matrix tablets

    Directory of Open Access Journals (Sweden)

    Md Imamul Islam

    2013-01-01

    Conclusion: The present study demonstrated that Diclofenac could be successfully prepared using an appropriate amount of Methocel K15 MCR® and CA in the form of matrix tablets with similar dissolution profile of patent product Voltaren SR® . The type of polymers used was found to induce a profound effect on release rate and mechanism.

  14. Clonidine Extended-Release Tablets for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Jain, Rakesh; Segal, Scott; Kollins, Scott H.; Khayrallah, Moise

    2011-01-01

    Objective: This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the…

  15. IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

    Science.gov (United States)

    Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

    2016-01-01

    In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

  16. A flexible-dose dispenser for immediate and extended release 3D printed tablets.

    Science.gov (United States)

    Pietrzak, Katarzyna; Isreb, Abdullah; Alhnan, Mohamed A

    2015-10-01

    The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91-95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment. Copyright © 2015. Published by Elsevier B.V.

  17. Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

    Science.gov (United States)

    Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

    2008-01-01

    The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

  18. Linking dissolution to disintegration in immediate release tablets using image analysis and a population balance modelling approach.

    Science.gov (United States)

    Wilson, David; Wren, Stephen; Reynolds, Gavin

    2012-01-01

    In order to achieve an improved understanding of disintegration and dissolution phenomena for an immediate release tablet formulation, a technique to monitor the number and size of particles entrained within the dissolution media was developed in combination with a population balancing model. Tablets were first characterized for crushing force, disintegration time and dissolution performance using standard USP methodologies. The performance of the tablets was then assessed using a new measurement system which links a "QicPic" particle imaging device to a USP dissolution vessel. This system enables us to measure the number and size of particles generated during tablet dissolution. The population balance mathematical model allowed a tablet erosion rate to be manipulated to fit the experimental data. Results showed that tablets with differing crushing forces showed different dissolution behaviors that could be explained by differing rates of particle release into the dissolution media. These behaviors were then successfully modeled to provide a description of the dissolution and disintegration behavior of the tablets in terms of a tablet erosion rate. A new approach was developed that allowed the description of the dissolution behaviors of the tablets in terms of the rate that they release particles into solution. This was then successfully modeled in terms of a tablet erosion rate.

  19. Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

    Directory of Open Access Journals (Sweden)

    Emami J.

    2008-05-01

    Full Text Available Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration. Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP, hydroxypropylmethyl cellulose (HPMC and sodium carboxymethyl cellulose (NaCMC in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients. Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics. Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K0 zero order release = 4.11 mg/h, MDT = 5.66 h and adhesive properties and did not show any interaction between polymers and drug based on

  20. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Erah

    surface, their drug release behavior appears simple, but ... matrix material for the formulation of ..... formulation F5 (,) and reference formulations. ( , □). 0. 50. 100. 150. 200. 250. 300. 0. 3. 6 .... Coviello T, Matricardi P, Marianecci C, Alhaique F.

  1. Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

    Science.gov (United States)

    Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

    2008-08-01

    A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

  2. A tandem queue with delayed server release

    OpenAIRE

    Nawijn, W.M.

    1997-01-01

    We consider a tandem queue with two stations. The rst station is an s-server queue with Poisson arrivals and exponential service times. After terminating his service in the rst station, a customer enters the second station to require service at an exponential single server, while in the meantime he is blocking his server in station 1 until he completes service in station 2, whereupon the server in station 1 is released. An analysis of the generating function of the simultaneous probability di...

  3. Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

    Science.gov (United States)

    Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

    2013-08-01

    The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

  4. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    International Nuclear Information System (INIS)

    Tan, Donna; Zhao Bin; Moochhala, Shabbir; Yang Yiyan

    2006-01-01

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved

  5. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  6. A study on programmed drug release from tablets

    NARCIS (Netherlands)

    Veen, Jacoba van der

    1993-01-01

    This thesis shows the extension of the applicability of the megaloporous system for drugs with different physico-chemical properties, like solubility and pK.. Procaine HC1, a highly soluble drug, can successfully be formulated in the programmed release megaloporous system, by using Carnauba wax,

  7. Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-01-01

    The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

  8. Intermediate release formulations of diclofenac potassium tablets for IVIVC.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Bushra, Rabia; Yasmin, Riffat; Siddiqui, Shehla; Alam, Zafar M

    2016-07-01

    In recent days response surface methodology (RSM) has widely been applied for development and optimization of cost effective formulations with required quality. Study comprised of three steps including micromeritic comparison of different powder blends of placebo and diclofenac potassium (DP), formulation designing with CCRD (Design Expert, version 7.0.0), and stability testing of selected formulations by using R Gui. Ten formulations (F11-F20) were developed using microcrystalline cellulose (Avicel PH-102) (X1) (13-72%), methocel K15M (X2) (6.59-23.4%) and magnesium stearate (X3) (1.32-4.68%), while responses were % friability and % drug release. Blending rate constant was determined at 3, 6, 9 and 12 minutes. The results of physicochemical parameters were found within acceptable limits. After in vitro testing at pH 1.2, pH 4.5 and pH 6.8, mechanism of drug release, kinetic analysis and statistical evaluation were carried out by model - independent, model-dependent and one-way ANOVA methods. Most formulations followed zero order kinetics at higher pH. Fickian release (0.326 ≤ n ≤0.449) was observed with β greater than 0.5 and less than 1. ANOVA indicated no significant variation within and between formulations as p-values were found to be > 0.05.

  9. Formulation And Evaluation Of Bilayer Tablet for Bimodal Release of Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Munira eMomin

    2015-07-01

    Full Text Available The aim of the present research was to develop a bilayer tablet of venlafexine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore Fenugreek Mucilage (FNM for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioahesive polymers like Hydroxy Propyl Methyl Cellulose, Carbopol and Xanthan Gum. The formulations were evaluated for swelling Index, ex-vivo bioadhesion, water uptake studies, in-vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4±0.023 gms and tablet adhesion retention time (24±2 hrs was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 =0.9913 via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1 and percent polymer replaced with FNM (X2 were taken as independent formulations variables. The selected responses, bioadhesion force (0.11-0.25±0.023gm, amount of drug released in 10 h, Y10 (78.20–95.78±1.24 % and bioadhesive strength, (19-24±2hrs presented good correlation with the selected independent variables. Statistical analysis (ANOVA of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05 in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release.

  10. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    Directory of Open Access Journals (Sweden)

    Kim JY

    2015-01-01

    Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

  11. Development of Modified-Release Tablets of Zolpidem Tartrate by Biphasic Quick/Slow Delivery System

    OpenAIRE

    Mahapatra, Anjan Kumar; Sameeraja, N. H.; Murthy, P. N.

    2014-01-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium s...

  12. Direct and indirect effects of paliperidone extended-release tablets on negative symptoms of schizophrenia

    OpenAIRE

    Bossie, Cynthia

    2008-01-01

    Ibrahim Turkoz, Cynthia A Bossie, Bryan Dirks, Carla M CanusoOrtho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ, USAAbstract: Direct and indirect effects of the new psychotropic paliperidone extended-release (paliperidone ER) tablets on negative symptom improvement in schizophrenia were investigated using path analysis. A post hoc analysis of pooled data from three 6-week, double-blind, placebo-controlled studies of paliperidone ER in patients experiencing acute exacerbation was con...

  13. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    OpenAIRE

    Kaleemullah, M.; Jiyauddin, K.; Thiban, E.; Rasha, S.; Al-Dhalli, S.; Budiasih, S.; Gamal, O.E.; Fadli, A.; Eddy, Y.

    2016-01-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop susta...

  14. WATER HYACINTH: A POSSIBLE ALTERNATIVE RATE RETARDING NATURAL POLYMER USED IN SUSTAINED RELEASE TABLET DESIGN

    Directory of Open Access Journals (Sweden)

    Sabera eKhatun

    2014-06-01

    Full Text Available In recent years natural polymers have been widely used, because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5%, 10%, 15%, 20%, 25% and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr’s Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR, Differential Scanning Calorimetry (DSC and Scanning Electron Microscopy (SEM studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37oC ± 0.5 temperature, for 8 hours. All the formulations comply with both BP and USP requirements, but among all the formulations F-1 (5% of Water hyacinth was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  15. Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

    Science.gov (United States)

    Gohel, M C; Patel, M M; Amin, A F

    2003-05-01

    This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

  16. Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design.

    Science.gov (United States)

    Khatun, Sabera; Sutradhar, Kumar B

    2014-01-01

    In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  17. Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

    Science.gov (United States)

    Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

    2011-04-01

    The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

  18. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    Science.gov (United States)

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

  19. A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

    Science.gov (United States)

    Vemula, Sateesh Kumar

    2015-12-01

    A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

  20. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  1. Drug kinetics release from Eudragit – Tenofovir@SiOC tablets

    Energy Technology Data Exchange (ETDEWEB)

    Tamayo, A., E-mail: aitanath@icv.csic.es [Ceramics and Glass Institute, CSIC, Madrid (Spain); Mazo, M.A. [Ceramics and Glass Institute, CSIC, Madrid (Spain); Veiga, M.D.; Ruiz-Caro, R.; Notario-Pérez, F. [Dpt. Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid (Spain); Rubio, J. [Ceramics and Glass Institute, CSIC, Madrid (Spain)

    2017-06-01

    A novel drug release system has been obtained in form of tablets from Eudragit® RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative purposes. The porous silicon oxycarbide presents a bimodal mesopore size distribution that is maintained after functionalization with amino groups. We have studied the adsorption kinetics and adsorption equilibrium when the materials are loaded with tenofovir and, in all cases, pseudo-second order kinetics and Langmuir isotherm have been revealed as the most representative models describing the kinetic and thermodynamic parameters. Besides, the tenofovir adsorption on these materials turns out to be a favorable process. In vitro release of tenofovir has been studied in simulated vaginal medium by applying different release models. Continuous tenofovir release for > 20 days has been obtained for the SiOC material functionalized with amine groups. We concluded that the drug release occurs in two steps that involve a drug diffusion step through the material pores and diffusion through the swollen polymer. The interactions between the tenofovir drug and de amine groups of the functionalized silicon oxycarbide also play an important role in the release process. - Highlights: • Kinetic and thermodinamic parameters of the adsorption of tenofovir on porous substrates have been obtained. • Sustained release of TFV for > 20 days in SVF when it is supported on SiOC and manufactured as Eudragit®RS-containing tablets. • Release described by a two-step process involving diffusion through SiOC matrix and subsequent diffusion through the polymer.

  2. Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

    Science.gov (United States)

    Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

    2012-07-01

    The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

  3. Layered lipid microcapsules for mesalazine delayed-release in children.

    Science.gov (United States)

    Balducci, Anna Giulia; Colombo, Gaia; Corace, Giuseppe; Cavallari, Cristina; Rodriguez, Lorenzo; Buttini, Francesca; Colombo, Paolo; Rossi, Alessandra

    2011-12-15

    The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4-5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

    Science.gov (United States)

    Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

    2007-07-18

    Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

  5. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

    Science.gov (United States)

    Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

    2004-03-01

    This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

  6. A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

    2016-11-01

    The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

  7. Preparation and In-Vitro Evaluation of Sustained Release Matrix Diclofenac Sodium Tablets Using HPMC KM 100 and Gums

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal, Raza Khan, Fazli Nasir, Jamshaid Ali Khan, Lateef Ahmad, Abad Khan, Yaser Shah

    2010-12-01

    Full Text Available Objectives: The impact of hydroxypropylmethyl cellulose(HPMC K 100M alone and in combination with the guar gum,xanthan gum and gum tragacanth on the release of the diclofenac sodium matrix tablets were evaluated.Materials and Methods: The granules were prepared using wet granulation method and compressed into tablets using different ratio of drug and gum ratio. The physical properties of the tablets were within acceptable pharmacopeial limits.The release profiles of the matrix tablets were evaluated in vitro,using USP dissolution apparatus II (paddle method.Results: The formulations containing HPMC K 100M drug ratio1:1.3 and 1:1.6 and formulations containing HPMC, gum and drug with different ratio also sustained the release of diclofenac sodium for 12 hours. The mechanism of drug release from the matrix tablets was studied using Zero order, First order, Higuchi and Korsmeyer’s models using regression coefficient method. The stability of the selected formulations was evaluated at 40˚C and 70% RH for 6 months.Conclusions: HPMC K100M alone and in combination with natural gums as the retarding material retarded the release upto 12 hours and showed little deviation from the theoretical release pattern.

  8. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

    Directory of Open Access Journals (Sweden)

    Tariq Ali

    2014-12-01

    Full Text Available The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2 results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

  9. Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

    Science.gov (United States)

    Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

    2013-04-01

    The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

  10. Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets.

    Science.gov (United States)

    Arafat, Basel; Wojsz, Magdalena; Isreb, Abdullah; Forbes, Robert T; Isreb, Mohammad; Ahmed, Waqar; Arafat, Tawfiq; Alhnan, Mohamed A

    2018-06-15

    Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  12. PREPARATION, CHARACTERIZATION AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRINS .4. DRUG-RELEASE FROM CAPSULES AND TABLETS CONTAINING AMYLODEXTRIN

    NARCIS (Netherlands)

    WIERIK, GHPT; EISSENS, AC; LERK, CF

    1993-01-01

    Linear dextrin (amylodextrin) and its soluble fraction were investigated for their suitability to enhance diazepam release from capsules and tablets. Drug release was analyzed in the USP XXI paddle apparatus and performed in phosphate buffer pH 6.8, with and without alpha-amylase, and in 0.1 N HCl

  13. A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole.

    Science.gov (United States)

    Ferrari, Priscileila Colerato; dos Santos Grossklauss, Dany Bruno Borella; Alvarez, Matheus; Paixão, Fabiano Carlos; Andreis, Uilian; Crispim, Alexandre Giordano; de Castro, Ana Dóris; Evangelista, Raul Cesar; de Arruda Miranda, José Ricardo

    2014-08-01

    Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets. The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery. Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release. The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%. The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

  14. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets.

    Science.gov (United States)

    Jayasree, J; Sivaneswari, S; Hemalatha, G; Preethi, N; Mounika, B; Murthy, S Vasudeva

    2014-10-01

    The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer - Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability.

  15. Kinetic Modelling of Drug Release from Pentoxifylline Matrix Tablets based on Hydrophilic, Lipophilic and Inert Polymers

    Directory of Open Access Journals (Sweden)

    Mircia Eleonora

    2015-12-01

    Full Text Available Pentoxifylline is a xanthine derivative used in the treatment of peripheral vascular disease, which because of its pharmacokinetic and pharmacologic profile is an ideal candidate for the development of extended release formulations. The aim of this study is to present a kinetic analysis of the pentoxifylline release from different extended release tablets formulations, using mechanistic and empirical kinetic models. A number of 28 formulations were prepared and analysed; the analysed formulations differed in the nature of the matrix forming polymers (hydrophilic, lipophilic, inert and in their concentrations. Measurements were conducted in comparison with the reference product Trental 400 mg (Aventis Pharma. The conditions for the dissolution study were according to official regulations of USP 36: apparatus no. 2, dissolution medium water, volume of dissolution medium is 1,000 mL, rotation speed is 50 rpm, spectrophotometric assay at 274 nm. Six mathematical models, five mechanistic (0 orders, 1st-order release, Higuchi, Hopfenberg, Hixson-Crowell and one empirical (Peppas, were fitted to pentoxifylline dissolution profile from each pharmaceutical formulation. The representative model describing the kinetics of pentoxifylline release was the 1st-order release, and its characteristic parameters were calculated and analysed.

  16. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

    Science.gov (United States)

    Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

    2016-01-01

    The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  17. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

    Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

    2018-04-12

    A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant.

    Science.gov (United States)

    Gaur, K Pawan; Soam, Kulwant; Gupta, S K; Dabral, Prashant

    2012-03-01

    The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  19. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

    Full Text Available The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  20. Modulation of the wettability of excipients by surfactant and its impacts on the disintegration and release of tablets.

    Science.gov (United States)

    Yang, Baixue; Xu, Lu; Wang, Qiuxiao; Li, Sanming

    2016-12-01

    To investigate the modulation of the wettability of excipients by different types of surfactants and its impacts on the disintegration of tablets and drug release. The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP. The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C 12 , including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate. The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent.

  1. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

    Science.gov (United States)

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

    The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

  2. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  3. Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

    Science.gov (United States)

    Kong, Hua; Yu, Fanglin; Liu, Yan; Yang, Yang; Li, Mingyuan; Cheng, Xiaohui; Hu, Xiaoqin; Tang, Xuemei; Li, Zhiping; Mei, Xingguo

    2018-01-01

    Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release. The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology. The expandable monolithic osmotic pump tablets containing nimodipine combined with poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic agent in semipermeable film were optimized. The release behavior was investigated both in vitro and in beagle dogs. It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained and complete release of nimodipine was also realized in beagles because the mean residence time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic pump tablets and the sustained release tablets in market. It was reasonable to believe that the sustained and complete release of poorly watersoluble nimodipine could be realized by using simple expandable monolithic osmotic pump technology combined with surfactant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Formulation, release characteristics, and bioavailability study of gastroretentive floating matrix tablet and floating raft system of Mebeverine HCl.

    Science.gov (United States)

    El Nabarawi, Mohamed A; Teaima, Mahmoud H; Abd El-Monem, Rehab A; El Nabarawy, Nagla A; Gaber, Dalia A

    2017-01-01

    To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin ® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the C max of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The t max was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action.

  5. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    Full Text Available Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD, pharmacokinetic (PK, and tolerability profiles of gemigliptin and extended-release metformin (metformin XR between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1 and metformin XR (500 mg ×2 were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4 activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs of FDC to separate tablet formulations and their 90% confidence intervals (CIs were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity

  6. Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler.

    Science.gov (United States)

    Tagami, Tatsuaki; Nagata, Noriko; Hayashi, Naomi; Ogawa, Emi; Fukushige, Kaori; Sakai, Norihito; Ozeki, Tetsuya

    2018-05-30

    3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

    International Nuclear Information System (INIS)

    Borin, M.T.; Khare, S.; Beihn, R.M.; Jay, M.

    1990-01-01

    The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-release tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study

  8. Pectin/anhydrous dibasic calcium phosphate matrix tablets for in vitro controlled release of water-soluble drug.

    Science.gov (United States)

    Mamani, Pseidy Luz; Ruiz-Caro, Roberto; Veiga, María Dolores

    2015-10-15

    Different pectin/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed in order to obtain controlled release of a water-soluble drug (theophylline). Swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralized water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid), to characterize the matrix tablets. When the pectin/ADCP ratio was ≥0.26 (P1, P2, P3 and P4 tablets) a continuous swelling and low theophylline dissolution rate from the matrices were observed. So, pectin gel forming feature predominated over the ADCP properties, yielding pH-independent drug release behavior from these matrices. On the contrary, pectin/ADCP ratios ≤0.11 (P5 and P6 tablets) allowed to achieve drug dissolution pH dependent. Consequently, the suitable selection of the pectin/ADCP ratio will allow to tailor matrix tablets for controlled release of water-soluble drugs in a specific manner in the gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

    Science.gov (United States)

    Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

    2011-06-01

    The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

  10. Development and validation of dissolution study of sustained release dextromethorphan hydrobromide tablets.

    Science.gov (United States)

    Rajan, Sekar; Colaco, Socorrina; Ramesh, N; Meyyanathan, Subramania Nainar; Elango, K

    2014-02-01

    This study describes the development and validation of dissolution tests for sustained release Dextromethorphan hydrobromide tablets using an HPLC method. Chromatographic separation was achieved on a C18 column utilizing 0.5% triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection wavelength was 280 nm. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The suitable conditions were clearly decided after testing sink conditions, dissolution medium and agitation intensity. The most excellent dissolution conditions tested, for the Dextromethorphan hydrobromide was applied to appraise the dissolution profiles. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by different operators. Mean Recovery was 101.82%. Intra precisions for three different concentrations were 1.23, 1.10 0.72 and 1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%, respectively. The method was successfully applied for dissolution study of the developed Dextromethorphan hydrobromide tablets.

  11. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

    Science.gov (United States)

    Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

    2015-07-15

    To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. An oral modified-release nifedipine tablet (Adalat LA) and its appearance on double contrast barium enema

    International Nuclear Information System (INIS)

    Bleehen, Robert E.

    2000-01-01

    Adalat LA 30 mg and 60 mg tablets are widely prescribed oral modified release nifedipine preparations with a porous, non-digestible plastic tablet coating which is required in order to effect the osmotically driven slow release mechanism. These tablets may therefore be seen anywhere along the gastrointestinal tract and are passed apparently whole in the faeces. An example of the appearance within the rectum of Adalat LA 30 (Bayer) on double contrast barium enema is shown and the main features described. A review of the literature is given. Recognition of the appearances during the barium enema examination will prompt those performing the procedure to question the drug history where relevant and will reduce the incidence of false-positive reporting. Bleehen, R.E. (2000)

  13. New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength.

    Science.gov (United States)

    Strübing, Sandra; Abboud, Tâmara; Contri, Renata Vidor; Metz, Hendrik; Mäder, Karsten

    2008-06-01

    The purpose of this study was to investigate the mechanism of floating and drug release behaviour of poly(vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon SR as an excipient for direct compression and different Kollicoat SR 30 D/Kollicoat IR coats varying from 10 to 20mg polymer/cm2 were investigated regarding drug release in 0.1N HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10mg polymer/cm2 SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics. Poly(vinyl acetate) proved to be an appropriate excipient to ensure safe and reliable drug release. Floating strength measurements offered the possibility to quantify the floating ability of the developed systems and thus to compare different formulations more efficiently. Benchtop MRI studies allowed a deeper insight into drug release and floating mechanisms noninvasively and continuously.

  14. Release mechanism of doxazosin from carrageenan matrix tablets: Effect of ionic strength and addition of sodium dodecyl sulphate.

    Science.gov (United States)

    Kos, Petra; Pavli, Matej; Baumgartner, Saša; Kogej, Ksenija

    2017-08-30

    The polyelectrolyte matrix tablets loaded with an oppositely charged drug exhibit complex drug-release mechanisms. In this study, the release mechanism of a cationic drug doxazosin mesylate (DM) from matrix tablets based on an anionic polyelectrolyte λ-carrageenan (λ-CARR) is investigated. The drug release rates from λ-CARR matrices are correlated with binding results based on potentiometric measurements using the DM ion-sensitive membrane electrode and with molecular characteristics of the DM-λ-CARR-complex particles through hydrodynamic size measurements. Experiments are performed in solutions with different ionic strength and with the addition of an anionic surfactant sodium dodecyl sulphate (SDS). It is demonstrated that in addition to swelling and erosion of tablets, the release rates depend strongly on cooperative interactions between DM and λ-CARR. Addition of SDS at concentrations below its critical micelle concentration (CMC) slows down the DM release through hydrophobic binding of SDS to the DM-λ-CARR complex. On the contrary, at concentrations above the CMC SDS pulls DM from the complex by forming mixed micelles with it and thus accelerates the release. Results involving SDS show that the concentration of surfactants that are naturally present in gastrointestinal environment may have a great impact on the drug release process. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 76 FR 53908 - Determination That OPANA ER (Oxymorphone Hydrochloride) Extended-Release Tablets, 7.5 Milligrams...

    Science.gov (United States)

    2011-08-30

    ... proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug. OPANA... relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for... withdrawal of OPANA ER (oxymorphone HCl) extended-release tablets, 7.5 mg and 15 mg, from sale. We have also...

  16. Modeling of drug release from multi-unit dosage tablets of theophylline

    African Journals Online (AJOL)

    To form the multi-unit dose tablets, granules of A and B were mixed together in various proportions in the ratios (A: B) 2:1, 1:1 and 1:2. The disintegration times of the tablets and their dissolution profiles were measured to investigate consistence with the model. The results showed that the tablets generally disintegrated ...

  17. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er-labeled sustained-release tablets

    International Nuclear Information System (INIS)

    Parr, A.F.; Beihn, R.M.; Franz, R.M.; Szpunar, G.J.; Jay, M.

    1987-01-01

    External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of 170 Er2O3 (enriched to greater than 96% 170 Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable 170 Er to radioactive 171 Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of 171 Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance

  18. Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

    Full Text Available The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9 reaching super case II transport, as the value of the release rate exponent (n varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05. The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.

  19. Film coated tablets (ColoPulse technology) for targeted delivery in the lower intestinal tract : influence of the core composition on release characteristics

    NARCIS (Netherlands)

    Schellekens, Reinout C. A.; Baltink, Jan H.; Woesthuis, Ellen M.; Stellaard, Frans; Kosterink, Jos G. W.; Woerdenbag, Herman J.; Frijlink, Henderik W.

    2010-01-01

    The design of a film coating technology which allows a tablet to deliver the drug in the ileocolonic segment would offer new treatment possibilities. The objective is to develop a platform technology that is suitable for a broad range of drug compounds. We developed a coated tablet with a delayed,

  20. Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

    Science.gov (United States)

    Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

    2017-05-01

    This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.

  2. 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.

  3. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers.

    Science.gov (United States)

    Wadher, K J; Kakde, R B; Umekar, M J

    2011-03-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  4. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    OpenAIRE

    Pallavi Yerramsetty; J. Vijaya Ratna; Venkata Ramana Reddy; Praveen Kumar

    2012-01-01

    Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by usin...

  5. Development of novel diclofenac potassium controlled release tablets by wet granulation technique and the effect of co-excipients on in vitro drug release rates.

    Science.gov (United States)

    Shah, Shefaatullah; Khan, Gul Majid; Jan, Syed Umer; Shah, Kifayatullah; Hussain, Abid; Khan, Haroon; Khan, Haroon; Khan, Haroon; Khan, Kamran Ahmad

    2012-01-01

    The aim of the present study was the formulation and evaluation of controlled release polymeric tablets of Diclofenac Potassium by wet granulation method for the release rate, release pattern and the mechanism involved in drug release. Formulations having three grades of polymer Ethocel (7P; 7FP, 10P, 10FP, 100P, 100FP) in several drugs to polymer ratios (10:3 and 10:1) were compressed into tablets using wet granulation method. Co-excipients were added to some selected formulations to investigate their enhancement effect on in vitro drug release patterns. In vitro drug release studies were performed using USP Method-1 (Rotating Basket method) and Phosphate buffer (pH 7.4) was used as a dissolution medium. The similarities and dissimilarities of release profiles of test formulations with reference standard were checked using f2 similarity factor and f1 dissimilarity factor. Mathematical/Kinetic models were employed to determine the release mechanism and drug release kinetics.

  6. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  7. Modulation of active pharmaceutical material release from a novel 'tablet in capsule system' containing an effervescent blend.

    Science.gov (United States)

    Gohel, Mukesh C; Sumitra G, Manhapra

    2002-02-19

    The objective of the present study was to obtain programmed drug delivery from hard gelatin capsules containing a hydrophilic plug (HPMC or guar gum). The significance of factors such as type of plug (powder or tablet), plug thickness and the formulation of fill material on the release pattern of diltiazem HCl, a model drug, was investigated. The body portion of the hard gelatin capsules was cross-linked by the combined effect of formaldehyde and heat treatment. A linear relationship was observed between weight of HPMC K15M and log % drug released at 4 h from the capsules containing the plug in powder form. In order to accelerate the drug release after a lag time of 4 h, addition of an effervescent blend, NaHCO(3) and citric acid, in the capsules was found to be essential. The plugs of HPMC in tablet form, with or without a water soluble adjuvant (NaCl or lactose) were used for obtaining immediate drug release after the lag time. Sodium chloride did not cause significant influence on drug release whereas lactose favourably affected the drug release. The capsules containing HPMC K15M tablet plug (200 mg) and 35 mg effervescent blend in body portion of the capsule met the selection criteria of less than 10% drug release in 4 h and immediate drug release thereafter. It is further shown that the drug release was also dependant on the type of swellable hydrophilic agent (HPMC or guar gum) and molecular weight of HPMC (K15M or 20 cPs). The results reveal that programmed drug delivery can be obtained from hard gelatin capsules by systemic formulation approach.

  8. Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

    Science.gov (United States)

    Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

    2017-11-01

    The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Preparation and in-vitro in-vivo evaluation of sustained release matrix diclofenac sodium tablets using PVP-K90 and natural gums.

    Science.gov (United States)

    Iqbal, Zafar; Khan, Raza; Nasir, Fazli; Khan, Jamshaid Ali; Rashid, Abdur; Khan, Abbas; Khan, Abad

    2011-10-01

    Conventional dosage form is nowadays mostly replaced by sustained release formulation in order to increase drug efficacy and patient compliance. The sustained release properties of the PVP K90 alone and in combination with guar gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium (100 mg/tablet) as a model drug. Tablets were processed using wet granulation method and evaluated for sustained drug release properties. The drug release from the formulations was studied in relationship with Commercially available Diclofenac Sodium SR, used as a reference tablets and results were expressed as similarity (f1) and differential factor (f2). The tablets prepared using PVP K90 160 mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations where the PVP K90 was partially replaced with different gums also sustained the release of drug for 12 hours. The release of the drug from these formulations mainly followed Higuchi model and super case-II and Non-Fickian diffusion. The in-vivo drug release was studied in healthy human volunteers using non-blinded cross over, two period design using Diclofenac Sodium SR Tablets as a reference drug. The relative bioavailability of the formulation containing PVP K90 and gum tragacanth was 0.91. The studies showed that the use of the PVP K90 in combination with gum tragacanth both in-vitro and in-vivo sustained the release of the drug.

  10. Differential pharmacokinetics of diclofenac potassium for oral solution vs immediate-release tablets from a randomized trial: effect of fed and fasting conditions.

    Science.gov (United States)

    Chen, Cuiping; Bujanover, Shay; Kareht, Stephanie; Rapoport, Alan M

    2015-02-01

    To compare the pharmacokinetics of, and food effect on, diclofenac potassium delivered as an oral solution vs an immediate-release tablet. Diclofenac potassium for oral solution is the only nonsteroidal anti-inflammatory drug approved as monotherapy for the acute treatment of migraine attacks with or without aura in adults 18 years of age or older. It is formulated with potassium bicarbonate as a buffering agent to raise the pH and consequently increase the aqueous solubility of diclofenac in the acidic environment of the stomach following oral administration. The dosage is 50 mg of powdered diclofenac potassium dissolved in 1 to 2 ounces (30 to 60 mL) of water prior to administration, with dosing time in relation to food intake not specified - this was the case for the pivotal efficacy and safety trials in subjects with acute migraine attacks in which the primary endpoints were achieved. For acute treatment of migraine attacks, rapid onset of pain relief is desirable and is likely related to a rapid appearance of an effective concentration of the drug in the systemic circulation. The rate at which an orally administered drug reaches the blood is affected by both its formulation and the presence of food in the stomach. The present study was designed to investigate the pharmacokinetics of 2 formulations of diclofenac potassium, an immediate-release tablet and an oral solution, and to ascertain the effect of food. This was an open-label, randomized, single-center, crossover trial in healthy volunteers. Subjects were randomized using computer-generated list to 1:1:1:1 ratio. They received a single 50-mg dose of diclofenac potassium in 4 sequences (ABCD, BADC, CDBA, and DCAB) during each of the 4 treatment periods. The 4 treatments were: A, oral solution fasting; B, tablet fasting; C, oral solution fed; and D, tablet fed. There was a ≥7-day washout period between dosing. Blood samples for pharmacokinetic analysis were taken for up to 12 hours post-dose and

  11. Food-dependent disintegration of immediate release fosamprenavir tablets: In vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system

    NARCIS (Netherlands)

    Brouwers, J.; Anneveld, B.; Goudappel, G.J.; Duchateau, G.; Annaert, P.; Augustijns, P.; Zeijdner, E.

    2011-01-01

    In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with

  12. Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

    Science.gov (United States)

    Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

    2011-03-01

    A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

  13. A new approach combining different MRI methods to provide detailed view on swelling dynamics of xanthan tablets influencing drug release at different pH and ionic strength.

    Science.gov (United States)

    Mikac, Ursa; Sepe, Ana; Kristl, Julijana; Baumgartner, Sasa

    2010-08-03

    The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. We have selected magnetic resonance imaging (MRI) as the method of choice for visualizing the dynamic processes occurring during the swelling of xanthan tablets in a variety of media. The aims were (i) to develop a new method using MRI for accurate determination of penetration, swelling and erosion fronts, (ii) to investigate the effects of pH and ionic strength on swelling, and (iii) to study the influence of structural changes in xanthan gel on drug release. Two dimensional (2D) MRI and one dimensional single point imaging (SPI) of swollen xanthan tablets were recorded, together with T(2) mapping. The border between dry and hydrated glassy xanthan-the penetration front-was determined from 1D SPI signal intensity profiles. The erosion front was obtained from signal intensity profiles of 2D MR images. The swelling front, where xanthan is transformed from a glassy to a rubbery state (gel formation), was determined from T(2) profiles. Further, the new combination of MRI methods for swelling front determination enables to explain the appearance of the unusual "bright front" observed on 2D MR images in tablets swollen in HCl pH 1.2 media, which represents the position of swelling front. All six media studied, differing in pH and ionic strength, penetrate through the whole tablet in 4h+/-0.3h, but formation of the gel layer is significantly delayed. Unexpectedly, the position of the swelling front was the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers. The latter are seen to be the consequence of the different hydrodynamic radii of the xanthan molecules, which affect the drug

  14. Interaction between fed and gastric media (ensure Plus) and different hypromellose based caffeine controlled release tablets; comparison and mechanistic study of caffeine release in fed and fasted media versus water using USP dissolution apparatus 3

    DEFF Research Database (Denmark)

    Franek, Frans; Holm, Per; Larsen, Frank

    2014-01-01

    , which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus® and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease...... using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus®, a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates...... the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration....

  15. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets

  16. Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

    Science.gov (United States)

    Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

    2017-01-01

    Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.

    Science.gov (United States)

    Hawi, Amale; Alcorn, Harry; Berg, Jolene; Hines, Carey; Hait, Howard; Sciascia, Thomas

    2015-04-08

    Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus.

  18. Interchangeability and comparative effectiveness between generic and brand montelukast immediate release tablets after a single oral administration in healthy volunteers.

    Science.gov (United States)

    Zaid, Abdel Naser; Mousa, Ayman; Ghazal, Nadia; Bustami, Rana

    2015-01-01

    Montelukast is a leukotriene receptor antagonist. The release of leukotrienes causes narrowing and constricting in the respiratory airways. Blocking the action of these leukotrienes, montelukast can be used for the prophylaxis and treatment of chronic asthma. The aim of this study was to evaluate the interchangeability and comparative effectiveness between a generic and a brand montelukast 10 mg immediate release tablets (Broncast(®) and Singulair(®), respectively) after a single oral dose among Arab Mediterranean volunteers. An open-label, randomized two-period crossover bioequivalence design was conducted in 31 healthy male volunteers with a 1 week washout between each study period and under fasting conditions. The plasma drug concentration was assessed by using a previously validated LC MS/MS method. The ratio between the generic and brand of geometric least squares means was reported for both generic and brand products. Moreover, an in vitro dissolution study was conducted on generic and brand tablets using three different pH media, and similarity and non-similarity factors (f2 and f1) were calculated. The used bioanalytical method was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient was close to 0.999 during the course of the study validation. Statistical comparison of the main pharmacokinetic parameters showed the inexistence of any significant difference between generic and the brand. The point estimates (ratios of geometric means) were 111.939, 111.711, and 112.169 % for AUC0-24, AUC0-∞, and Cmax, respectively. The 90 % confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00 % as specified by the FDA and EMA for bioequivalence studies. F2 and f1 were higher than 50 and lower than 15, respectively in all selected pH media. Broncast(®) immediate release film coated tablets (10 mg/tablet) are bioequivalent to Singulair(®) immediate release film coated tablets (10 mg/tablet), with a

  19. Effect Of Ether Derivative Cellulose Polymers On Hydration, Erosion And Release Kinetics Of Diclofenac Sodium Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Muhammad Akhlaq*1,2, Gul Majid Khan1 , Abdul Wahab1, Waqas Rabbani1, Abid Hussain1, Asif Nawaz1, & Alam Zeb1

    2011-09-01

    Full Text Available Objectives: The work aims to investigate the effect ofhydrophilic and hydrophobic polymers swelling and erosionon the release behaviour of DCL-Na from controlled matrixtablets prepared by direct compression and wet-granulationtechniques.Materials and Methods: Powder preformulation studies wereconducted. Tablets were prepared by direct compressiontechnique and their physicochemical properties wereevaluated. Drug-polymer interaction was analyzed by FTIRspectroscopy. The in-vitro drug release study was conductedusing phosphte buffer pH 7.4 as dissolution medium anddifferent kinetic parameters were applied.Results and Discussion: F-1 and F-5 containing ethycelluloseprepared by direct compression and wet granulationtechniques released 94 % and 84 % drug after 24hrs, while F-2and F-6 containing hydroxypropylmethylcellulose polymerprepared by direct compression and wet granulation released98.46 % and 91.25 % drug after within 24 hrs respectively.Ethylcellulose and hydroxypropylmethylcellulose based matrixtablets showed the best anomalous drug release behaviour,with the release exponents “ n ” ranging from 0.685 to 0.809.Conclusion: It has been concluded that ethylcellulose etherderivative polymer is used to prepare oral controlled releasematrix tablet of diclofenac sodium. Fickian drug diffusion,polymer hydration and erosion mechanisms occurredsimultaneously and were considered as the main drug releasecontrolling factors.

  20. Influence of water-soluble channeling agents on the release of diclofenac sodium from Irvingia malayana wax matrix tablets.

    Science.gov (United States)

    Yotsawimonwat, Songwut; Charumanee, Suporn; Kaewvichit, Sayam; Sirithunyalug, Jakkapan; Sirisa-Ard, Panee; Piyamongkol, Sirivipa; Siangwong, Kulthawat

    2017-05-01

    Irvingia malayana wax (IW) is majorly composed of esters of medium chain fatty acids. Its melting point is low and closed to the body temperature. This study aimed at investigating the potential of IW as a matrix-forming agent and evaluate the effect of soluble channeling agents on the release of diclofenac sodium (DS) from IW matrix tablets. The preformulation study by infrared spectroscopy and differential scanning calorimetry showed no incompatibility between IW and DS or soluble channeling agents, namely PEG 4000, PEG 6000 and lactose. IW retarded the release of DS from the matrix tablets more efficiently than carnauba wax due to its greater hydrophobicity and its ability to become partial molten wax at 37° C. Factors affecting the release of DS from IW matrix were drug concentrations, and types and concentrations of channeling agents. The release of DS significantly improved when DS concentration reached approximately 33%. The fast dissolving channeling agent, lactose, could enhance the drug release rate more effectively than PEG 4000 and PEG 6000, respectively. The linear relationship between the DS release rate and the concentration of the chosen channeling agent, PEG 6000, was found (r 2 =0.9866).

  1. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

    Directory of Open Access Journals (Sweden)

    Mariam Vbamiunomhene Lawal

    2015-07-01

    Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  2. Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

    Science.gov (United States)

    Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

    2017-07-01

    This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

  3. Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy.

    Science.gov (United States)

    Arvidsson, J; Nilsson, H L; Sandstedt, P; Steinwall, G; Tonnby, B; Flesch, G

    1995-03-01

    A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.

  4. Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

    Science.gov (United States)

    Solanki, Nayan G; Tahsin, Md; Shah, Ankita V; Serajuddin, Abu T M

    2018-01-01

    The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon ® VA64, Kollicoat ® IR, Affinsiol ™ 15 cP, and HPMCAS either individually or as binary blends (Kollidon ® VA64 + Affinisol ™ 15 cP, 1:1; Kollidon ® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon ® VA64-Affinisol ™ 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon ® VA64 and Affinisol ™ 15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

    Directory of Open Access Journals (Sweden)

    Volnei Jose Tondo Filho

    2014-09-01

    Full Text Available The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain of polymer was similar to that ofthe reference drug.

  6. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Science.gov (United States)

    2010-04-01

    ... response within 2 to 3 days, reevaluate therapy. Do not crush tablets. Treated animals must not be... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520...

  7. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

    Directory of Open Access Journals (Sweden)

    Ahmed SM

    2016-12-01

    Full Text Available Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol. Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031.The pharmacokinetic results indicated that the area under the curve (AUC0–∞ of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton® and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022. Conclusion: The prepared floating tablets of ITO HCl (F10 could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailability

  8. Dalfampridine extended release tablets: 1 year of postmarketing safety experience in the US

    Directory of Open Access Journals (Sweden)

    Jara M

    2013-03-01

    Full Text Available Michele Jara,1 Graham Barker,2 Herbert R Henney 3rd1 1Acorda Therapeutics, Inc, Ardsley, NY, USA; 2Biogen Idec, Inc, Maidenhead, Berkshire, UK Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine in some countries were approved in the US to improve walking in patients with multiple sclerosis, as demonstrated by improvement in walking speed. Postmarketing safety experience is available from exposure of approximately 46,000 patients in the US from product approval through March 2011. Objective: To provide a descriptive analysis of all spontaneously reported postmarketing adverse events (AEs for dalfampridine-ER since product launch. Methods: AE data were extracted from the safety database from product launch through March 31, 2011; AEs were classified using the Medical Dictionary for Regulatory Activities. Seizure cases were reviewed for patient demographics, time to event from treatment onset, and presence of additional risk factors. Results: The most frequently reported postmarketing AEs were similar to those reported during clinical development: dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, asthenia, and back pain (all included in US product labeling. New clinically significant findings are related to lack of efficacy and inappropriate dosing. Of the approximately 46,000 patients exposed, 85 seizures were reported (~5.4/1000 patient-years, of which 82 were reported or confirmed by a health care practitioner (~5.2/1000 patient-years. Beyond the intrinsic multiple sclerosis-related seizure risk, more than half of the 85 cases (62% had an additional potential risk factor for seizure including a previous history of convulsions, renal impairment, incorrect dosing, or use of concurrent medications with a labeled seizure risk. Duration of treatment prior to the seizure ranged from one dose to 365 days; 26/85 (31% patients suffered a seizure

  9. THE PROCESS OF MASS TRANSFER ON THE SOLID-LIQUID BOUNDARY LAYER DURING THE RELEASE OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE FROM TABLETS IN A PADDLE APPARATUS.

    Science.gov (United States)

    Kasperek, Regina; Zimmer, Lukasz; Poleszak, Ewa

    2016-01-01

    The release study of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) from two formulations of the tablets in the paddle apparatus using different rotation speeds to characterize the process of mass transfer on the solid-liquid boundary layer was carried out. The dissolution process of active substances was described by values of mass transfer coefficients, the diffusion boundary layer thickness and dimensionless numbers (Sh and Re). The values of calculated parameters showed that the release of DIC and PAP from tablets comprising potato starch proceeded faster than from tablets containing HPMC and microcrystalline cellulose. They were obtained by direct dependencies between Sh and Re in the range from 75 rpm to 125 rpm for both substances from all tablets. The description of the dissolution process with the dimensionless numbers make it possible to plan the drug with the required release profile under given in vitro conditions.

  10. Investigation of an artificial intelligence technology--Model trees. Novel applications for an immediate release tablet formulation database.

    Science.gov (United States)

    Shao, Q; Rowe, R C; York, P

    2007-06-01

    This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

  11. Formulation and Study of Some Controlled Release Tablets with Pentoxifylline Based on Hydroxypropylcellulose Matrix Obtained by Wet Granulation Method with PEG 6000

    Directory of Open Access Journals (Sweden)

    Gabriel Hancu

    2011-01-01

    Full Text Available In this work three formulations of modified release tablets
    containing pentoxifylline 400 mg/tablet were obtained. Hydroxypropylcellulose (HPC in di®erent ratios was used as hydrophilic matrix agent. The pentoxifylline inclusion in the matrix has been carried out by water granulation, using PEG 6000 as binder. Tablets were obtained with a single station
    tablet machine (Korsch, using standard pressure, and obtaining tablets with 13 mm diameter, 800 mg weight and 400 mg pentoxifylline per tablet. The weight uniformity, friability, hardness, thickness and disintegration of tablets were determined according to the stipulations of the 2001 Supplement of the Romanian Pharmacopoeia Xth edition. The experimental formulations with 400 mg pentoxifylline/tablet were studied by comparing them to the industrial reference product, Trental 400 mg (Aventis Pharma and in according
    to the stipulations of Romanian Pharmacopoeia Xth edition, USP 27 and European Pharmacopoeia 5th edition. Every determination was performed using 20 tablets. We followed the comparison between dissolution profiles of slow release tablets containing pentoxifylline based on hydrophilic matrix. The dissolution studies were performed using the method from USP 24, using the paddle apparatus, and water as medium of dissolution at 37+/-0,5 Celsius degrees, at a rotation speed of 50 rpm. The determination was performed by spectrofotometric as say in UV at 274 nm. It was noticeable that regarding the weight uniformity, friability, hardness, thickness and disintegration the proposed formulations are comparable with the industrial reference product (Trental, 400 mg and are in agreement with the stipulations of the Romanian Pharmacopoeia Xth edition and European Pharmacopoeia 5th edition. The analysis of dissolution profiles showed that all formulations exhibit slow release.

  12. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Shah

    2012-01-01

    Full Text Available The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4 using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including max, max and AUC0- were compared which showed an optimized max and max (<0.05. A good correlation was obtained between in vitro

  13. [The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

    Science.gov (United States)

    Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2012-01-01

    Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration

  14. Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

    Science.gov (United States)

    Shahiwala, Aliasgar; Zarar, Aisha

    2018-01-01

    In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Low molecular weight polylactic acid as a matrix for the delayed release of pesticides.

    Science.gov (United States)

    Zhao, Jing; Wilkins, Richard M

    2005-05-18

    Low molecular weight polylactic acid (LMW PLA) was used as a matrix to formulate biodegradable matrix granules and films with bromacil using a melt process. The compatibility of the PLA with bromacil was evaluated. The release characteristics of the formulations were investigated in vitro. The degradation and erosion of the formulations were monitored by pH and gravimetric analysis during the course of release. Various granules and films had similar biphasic release patterns, a delayed release followed by an explosive release. The release rates were independent of bromacil content in the matrix, but varied with the geometry of matrices. The mechanisms of diffusion and erosion were involved in the release. The delayed release of the formulations was dominantly governed by the degradation and erosion of PLA. LMW PLA underwent bulk erosion. LMW PLA-based matrix formulations could thus be useful for the application of pesticides to sensitive targets such as seed treatment.

  16. Research Article. Kinetics and Mechanism of Drug Release from Loratadine Orodispersible Tablets Developed without Lactose

    Directory of Open Access Journals (Sweden)

    Ciurba Adriana

    2017-03-01

    Full Text Available Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance. Materials and methods: Seven compositions (F1-F7 of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The tablets had been studied in terms of their pharmacotechnical characteristics, by determining: the weight uniformity of the tablets, their friability, breaking strength and disintegration time, drug content and the dissolution profile of loratadine. The statistical analyses were performed with GraphPad Prism Software Inc. As dependent variables, both the hardness of the tablets and their disintegration ability differ between batches due to their compositional differences (as independent variables. DDSolver were used for modeling the kinetic of the dissolution processes by fitting the dissolution profiles with time-dependent equations (Zero-order, First-order, Higuchi, Korsmeyer-Peppas, Peppas-Sahlin. Results: All proposed formulas shows rapid disintegration, in less than 15 seconds, and the dissolution loratadine spans a period of about 10 minutes. Akaike index as well as R2 adjusted parameter have demonstrated that the studied dissolution profiles are the best fitted by Zero-order kinetic. Conclusion: In conclusion, association of croscarmellose sodium (7.5% with pre-gelatinized starch (6% as superdisintegrants and mannitol as the binder agent (35%, positively influences the dissolution properties of loratadine from orally fast dispersible tablets.

  17. Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications.

    Science.gov (United States)

    Lima, Dione Marçal; dos Santos, Leandro Dias; Lima, Eliana Martins

    2008-08-05

    Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20 mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug.

  18. Optimization of tenofovir release from mucoadhesive vaginal tablets by polymer combination to prevent sexual transmission of HIV.

    Science.gov (United States)

    Notario-Pérez, Fernando; Cazorla-Luna, Raúl; Martín-Illana, Araceli; Ruiz-Caro, Roberto; Tamayo, Aitana; Rubio, Juan; Veiga, María-Dolores

    2018-01-01

    The use of sustained-release mucoadhesive vaginal tablets of antiretroviral drugs as microbicidal formulations can be an effective strategy for reducing the sexual transmission of HIV from men to women, which is a main problem particularly in low- and middle-income countries. Different polymers (hydroxypropylmethyl cellulose (HPMC), chitosan, guar gum and Eudragit ® RS) have proven some good features for this purpose. At this work, these polymers have been combined in pairs in different proportions to enhance the advantages offered by each one individually. The in vitro release of tenofovir from the matrices, ex vivo mucoadhesive capacity (evaluated on vaginal mucosa) and the degree of swelling in simulated vaginal fluid have been assessed. A multimodal pore size distribution is observed in porosimetry studies -carried out with swelling witnesses-, due to the contribution of polymers with different swelling behaviour to the pore formation, and it is corroborated by scanning electron microscopy. X-ray diffraction technique confirms the changes in crystallinity of the formulation after swelling. We can report that the combination of HPMC and chitosan in the same formulation may be useful for the prevention of sexual transmission of HIV, since tablets can be obtained that remain adhered to the vaginal mucosa for 96h, so the drug is released in a sustained manner for 72h. When the formulation contains more chitosan than HPMC the swelling is moderate, making it more comfortable for women to apply. Copyright © 2017. Published by Elsevier Ltd.

  19. Validated, Ultra Violet Spectroscopy method for the Dissolution study of Mycophenolate mofetil immediate release 500mg tablets

    OpenAIRE

    Surajpal P. Verma; Ozair Alam; Pooja Mullick; Nadeem Siddiqui; Suroor A. Khan

    2008-01-01

    A simple, selective and precise dissolution method was developed and validated for the Mycophenolate mofetil immediate release tablets. The method employed dissolution medium 0.1N HCl (pH1.2) and volume 900ml with USP-II apparatus (Paddle). Detection was made by measuring the absorbance on UV at the [lambda]~max~ 250nm. The method show the linearity in the range of conc. 5[micro]g/ml to 40[micro]g/ml with r^2^=0.999. The method is also validated as per International Conference of Harmonizatio...

  20. Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

    Science.gov (United States)

    Desai, Divyakant; Wong, Benjamin; Huang, Yande; Tang, Dan; Hemenway, Jeffrey; Paruchuri, Srinivasa; Guo, Hang; Hsieh, Daniel; Timmins, Peter

    2015-01-01

    To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

  1. Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

    Science.gov (United States)

    Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

    2018-04-01

    Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

  2. Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

    Science.gov (United States)

    Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

    2017-12-01

    Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically

  3. Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

    Science.gov (United States)

    Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

    2012-12-01

    The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

  4. Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

    Science.gov (United States)

    Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

    2018-02-01

    Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

  5. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

    Science.gov (United States)

    Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

    2016-11-20

    This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief

    Directory of Open Access Journals (Sweden)

    Inoue S

    2017-08-01

    Full Text Available Satoshi Inoue,1 Yoji Saito,2 Satoru Tsuneto,3 Etsuko Aruga,4 Azusa Ide,1 Yasuyuki Kakurai5 1Clinical Development Department, R&D Division, Daiichi Sankyo, Tokyo,2Department of Anesthesiology, Faculty of Medicine, Shimane University, Shimane, 3Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 4Department of Palliative Medicine, School of Medicine, Teikyo University, Tokyo, 5Biostatistics and Data Management Department, R&D Division, Daiichi Sankyo, Tokyo, Japan Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methods: This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88 or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93 orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone. The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS score from baseline to completion of treatment.Results: The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets

  7. Food-dependent disintegration of immediate release fosamprenavir tablets: in vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system.

    Science.gov (United States)

    Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn

    2011-02-01

    In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Formulation and evaluation of a bilayer tablet comprising of diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core

    OpenAIRE

    Abbas, Jabbar; Bashir, Sajid; Samie, Muhammad; Laghari, Sadaf

    2017-01-01

    Diclofenac a phenylacetic acid derivative has long been used as an anti-inflammatory and analgesic drug to treat certain conditions however its sustained release formulation with immediate release loading dose is desirable. The rationale of the current work was to develop and evaluate bilayer tablets with diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core. The diclofenac sodium core was prepared by wet granulation method while the...

  9. Formulation design of an HPMC-based sustained release tablet for pyridostigmine bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution properties.

    Science.gov (United States)

    Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

    2007-11-01

    Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 2(3) full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/- 0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to 1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

  10. Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

    Directory of Open Access Journals (Sweden)

    Ruggero Bettini

    2014-01-01

    Full Text Available In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

  11. The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

    2016-06-01

    In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

  12. Measurement uncertainty of dissolution test of acetaminophen immediate release tablets using Monte Carlo simulations

    Directory of Open Access Journals (Sweden)

    Daniel Cancelli Romero

    2017-10-01

    Full Text Available ABSTRACT Analytical results are widely used to assess batch-by-batch conformity, pharmaceutical equivalence, as well as in the development of drug products. Despite this, few papers describing the measurement uncertainty estimation associated with these results were found in the literature. Here, we described a simple procedure used for estimating measurement uncertainty associated with the dissolution test of acetaminophen tablets. A fractionate factorial design was used to define a mathematical model that explains the amount of acetaminophen dissolved (% as a function of time of dissolution (from 20 to 40 minutes, volume of dissolution media (from 800 to 1000 mL, pH of dissolution media (from 2.0 to 6.8, and rotation speed (from 40 to 60 rpm. Using Monte Carlo simulations, we estimated measurement uncertainty for dissolution test of acetaminophen tablets (95.2 ± 1.0%, with a 95% confidence level. Rotation speed was the most important source of uncertainty, contributing about 96.2% of overall uncertainty. Finally, it is important to note that the uncertainty calculated in this paper reflects the expected uncertainty to the dissolution test, and does not consider variations in the content of acetaminophen.

  13. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  14. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    OpenAIRE

    Fatemeh Pourhashem; Mohammad Reza Avadi

    2016-01-01

    The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M) as release retardant, polyvinyl pyrrolidone (PVP k30) as binder and Magnesium S...

  15. Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Kim, Yo Han; Kim, Mi Jo; Lee, Shi Hyang; Kim, Jeong-Ae; Kim, Bogyeong; Lim, Hyeong-Seok; Bae, Kyun-Seop

    2014-05-01

    For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study. Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component. The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

  16. A double-blind comparison of slow-release and standard tablet formulations of fentiazac in the treatment of patients with tendinitis and bursitis.

    Science.gov (United States)

    Ginsberg, F; Famaey, J P

    1985-01-01

    Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac, given once daily, with the standard tablet formulations of 100 mg, given 4-times daily, or 200 mg, given twice daily. A total of 60 patients suffering from acute bicipital tendinitis and/or subdeltoid bursitis was studied, 15 patients on the slow-release and 15 on one of the two standard tablets in each of the two trials. Patients were assessed on entry and at Days 7 and 14 of treatment. The results in both studies showed that there was significant improvement in tenderness, pain on movement, overall pain and in the range of movement after treatment, there being no significant difference between those receiving the slow-release form or the standard tablets. Tolerance was good in all groups and only a few minor or moderate side-effects, mainly of a gastro-intestinal type, were reported.

  17. Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets.

    Science.gov (United States)

    Markl, Daniel; Yassin, Samy; Wilson, D Ian; Goodwin, Daniel J; Anderson, Andrew; Zeitler, J Axel

    2017-06-30

    Oral dosage forms are an integral part of modern health care and account for the majority of drug delivery systems. Traditionally the analysis of the dissolution behaviour of a dosage form is used as the key parameter to assess the performance of a drug product. However, understanding the mechanisms of disintegration is of critical importance to improve the quality of drug delivery systems. The disintegration performance is primarily impacted by the hydration and subsequent swelling of the powder compact. Here we compare liquid ingress and swelling data obtained using terahertz pulsed imaging (TPI) to a set of mathematical models. The interlink between hydration kinetics and swelling is described by a model based on Darcy's law and a modified swelling model based on that of Schott. Our new model includes the evolution of porosity, pore size and permeability as a function of hydration time. Results obtained from two sets of samples prepared from pure micro-crystalline cellulose (MCC) indicate a clear difference in hydration and swelling for samples of different porosities and particle sizes, which are captured by the model. Coupling a novel imaging technique, such as TPI, and mathematical models allows better understanding of hydration and swelling and eventually tablet disintegration. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  18. A new generation of starch products as excipient in pharmaceutical tablets .2. High surface area retrograded pregelatinized potato starch products in sustained-release tablets

    NARCIS (Netherlands)

    TeWierik, GHP; Eissens, AC; ArendsScholte, AW; Lerk, CF

    1997-01-01

    A new linear short-chain starch product was prepared by gelatinization of potato starch followed by enzymatic degradation, precipitation (retrogradation) and filtration. A high specific surface area was subsequently created by washing with ethanol or acetone or freeze-drying. Tablets compressed from

  19. Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Hanif, Muhammad; Bushra, Rabia; Naz, Asia; Khursheed, Raheela

    2016-09-01

    This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test (F4) tablet formulation with reference product (Caflam). Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 µg.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test (F4) and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using KineticaTM 4.4.1 (Thermo Electron Corp. USA). Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for Cmaxcalc, Tmaxcalc, AUC0-∞, AUCtot and AUClast using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC0-∞ (0.997-1.024), AUCtot (1.004-1.031), AUClast (0.997 -1.024), Cmaxcalc (0.994-1.007) and Tmaxcalc (0.996-1.013) for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated.

  20. Quality-by-design III: application of near-infrared spectroscopy to monitor roller compaction in-process and product quality attributes of immediate release tablets.

    Science.gov (United States)

    Kona, Ravikanth; Fahmy, Raafat M; Claycamp, Gregg; Polli, James E; Martinez, Marilyn; Hoag, Stephen W

    2015-02-01

    The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller compaction process parameters, compression force (CFt), and formulation variables identified from our earlier studies were evaluated in more detail. Multivariate principal component analysis (PCA) and partial least square (PLS) models were developed during the development stage and used as a control tool to predict the quality of granules and tablets. Validated models were used to monitor and control batches manufactured at different sites to assess their robustness to change. The results showed that roll pressure (RP) and CFt played a critical role in the quality of the granules and the finished product within the range tested. Replacing binder source did not statistically influence the quality attributes of the granules and tablets. However, lubricant type has significantly impacted the granule size. Blend uniformity, crushing force, disintegration time during the manufacturing was predicted using validated PLS regression models with acceptable standard error of prediction (SEP) values, whereas the models resulted in higher SEP for batches obtained from different manufacturing site. From this study, we were able to identify critical factors which could impact the quality attributes of the CIP IR tablets. In summary, we demonstrated the ability of near-infrared spectroscopy coupled with chemometrics as a powerful tool to monitor critical quality attributes (CQA) identified during formulation development.

  1. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    , its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting...

  2. Simultaneous release of diclofenac sodium and papaverine hydrochloride from tablets and pellets using the flow-through cell apparatus described by dimensionless equations.

    Science.gov (United States)

    Kasperek, Regina

    2011-01-01

    The release of diclofenac sodium and papaverine hydrochloride from tablets and pellets using the flow-through cell apparatus was studied. The influence of excipients and of a size of the solid dosage forms on the amount of the released substances at the intervals of time using the different rates of flow of the dissolution medium was investigated. Physical parameters corresponding to the dissolution process as the mass transfer coefficient, the thickness of the boundary diffusion layer and the concentration of the saturated solution at this layer were calculated. The results of release were described by dimensionless equations.

  3. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    OpenAIRE

    Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman

    2016-01-01

    Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...

  4. Development and in vitro evaluation of sustained release multiparticulate tablet of freely water soluble drug

    Directory of Open Access Journals (Sweden)

    Ashlesha Pravin Pandit

    2010-09-01

    Full Text Available Blends of aqueous dispersion of a hydrophobic and hydrophilic polymer, namely Surelease®: hydroxypropyl methylcellulose (Surelease®: HPMC E15 were used as coating materials to control the drug release from coated pellets of the highly water soluble drug metoprolol succinate. Varying the polymer blends, ranges of drug release patterns were obtained at pH 6.8. The present study dealt with diffusion of drug through plasticized Surelease®/ hydroxypropyl methylcellulose (HPMC E15 films prepared by coating of drug and polymers onto non-pareil seeds using the solution layering technique. The release of metoprolol succinate from coated pellets was decreased with increased coating load of polymer. The optimized formulation was obtained by 3² full factorial design. The release profile revealed that the optimized formulation follows zero order release kinetics. The stability data showed no interaction for storage at 25ºC and 60% relative humidity.Misturas das dispersões aquosas de polímero hidrofóbico e de polímero hidrofílico, a saber, Surelease®: hidroxipropil metilcelulose (Surelease®: HPMC E15, foram utilizadas como material de revestimento para controlar a liberação de fármacos de péletes revestidos de fármaco altamente solúvel, o succinato de metoprolol. Variando as misturas de polímeros, obtiveram-se faixas de padrão de liberação do fármaco em pH 6,8. O presente estudo tratou da difusão do fármaco através de filmes de Surelease®/hidroxipropil metilcelulose(HPMC E15, preparados pelo revestimento do fármaco e dos polímeros em sementes nonpareil, utilizando técnica de solução em camada. A liberação de succinato de metoprolol dos péletes revestidos diminuiu com o aumento da carga de polímero de revestimento. A formulação otimizada foi obtida por planejamento fatorial 3². O perfil de liberação revelou que a formulação otimizada segue a cinética de liberação de ordem zero. Os dados de estabilidade mostraram n

  5. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Science.gov (United States)

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  6. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets.

    Science.gov (United States)

    Devjak Novak, S; Šporar, E; Baumgartner, S; Vrečer, F

    2012-07-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by different manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of active pharmaceutical ingredients (API). This study investigates whether HPMC manufactured by two manufacturers using different chemical procedures differs in particle-size distribution, particle shape, particle morphology, chemical composition, and dissolution of diclofenac sodium as a model drug. NIR spectroscopy was introduced and calibration models were developed to detect physical differences among HPMC batches from two different origins. The physical differences between HPMC samples were additionally confirmed with scanning electron microscopy (SEM), gas chromatography (GC) measurements, and dissolution testing of hydrophilic matrix tablets. Our results prove that, even if HPMC polymers manufactured from two different sources comply with the pharmacopeial specification, they significantly differ in physicochemical properties and thus influence the properties of the formulated dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

    Science.gov (United States)

    Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

    2015-01-01

    The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p valsartan β cyclodextrin complex was significantly higher (p valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

  8. The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

    Science.gov (United States)

    Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

    2017-08-01

    The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

  9. Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.

    Science.gov (United States)

    Rajkumar, Arthi D; Reynolds, Gavin K; Wilson, David; Wren, Stephen; Hounslow, Michael J; Salman, Agba D

    2016-09-01

    tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

    Science.gov (United States)

    Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

    2017-01-01

    Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

  11. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  12. Studies on Gastroselective Famotidine Floating Tablets for Gastric Ulcers and Effect of Polymeric Excipients on Drug Release.

    OpenAIRE

    Putta Rajesh Kumar

    2012-01-01

    The present investigation was planned to formulate effervescent floating, gastroretentive guar gum tablets containing famotidine, which can be useful in the treatment of gastric ulcer. The investigations carried out on various formulations resulted in totally four formulations obeying zero order kinetics. The study on rheological characteristics of powder bed indicated that, all the granules were freely flowing and compressible; density of all the tablets was less than 1, thereby assisting in...

  13. Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

    Science.gov (United States)

    Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

    2017-10-01

    The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

  14. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  15. Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

    Science.gov (United States)

    Markl, Daniel; Sauerwein, Johanna; Goodwin, Daniel J; van den Ban, Sander; Zeitler, J Axel

    2017-05-01

    The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. The disintegration time (R 2  = 0.86) and API dissolved after 15 min (R 2  = 0.96) linearly correlates with the effective refractive index, n eff , measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff , we observed a better correlation with dissolution after 20 min (R 2  = 0.96) and a weaker correlation with disintegration (R 2  = 0.83) compared to n eff . The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to

  16. Formulation of a modified release metformin. HCl matrix tablet: influence of some hydrophilic polymers on release rate and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

    Full Text Available Metformin hydrochloride is an antidiabetic agent which improves glucose tolerance in patients with type 2 diabetes and reduces basal plasma levels of glucose. In this study, a simplex centroid experimental design with 69 runs was used to select the best combination of some hydrophilic polymers that rendered a 24 h in-vitro release profile of metformin.HCl. The Korsmeyer-Peppas model was used to model the dissolution profiles since it presented the best fit to the experimental data. Further, a cubic model predicted the best formulation of metformin.HCl containing polyvinyl pyrrolidone, ethyl cellulose, hydroxypropyl methyl cellulose, carrageenan, sodium alginate, and gum arabic at 6.26, 68.7, 6.26, 6.26, 6.26 and 6.26 % levels, respectively. The validation runs confirmed the accuracy of the cubic model with six components for predicting the best set of components which rendered a once-a-day modified release hydrophilic matrix tablet in compliance with the USP specifications.O cloridrato de metformina é um agente antidiabético que melhora a tolerância à glicose em pacientes com diabetes tipo 2 e reduz os níveis plasmáticos basais de glicose. Neste estudo, um projeto experimental do tipo "centróide simplex" com 69 tomadas foi usado para selecionar a melhor combinação de alguns polímeros hidrofílicos que gerou um perfil de liberação da metformina.HCl de 24 horas. O modelo Korsmeyer-Peppas foi usado para modelar os perfis de dissolução, uma vez que apresentou os melhores ajustes aos dados experimentais. Além disso, um modelo cúbico previu a melhor formulação de metformina.HCl sendo aquela contendo polivinilpirrolidona, etilcelulose, hidroxipropilmetil celulose, carragena, alginato de sódio e goma arábica nos níveis 6.26, 68.7, 6.26, 6.26, 6.26 e 6.26 %, respectivamente. As corridas de validação confirmaram a precisão do modelo cúbico com os seis componentes para prever o melhor conjunto de componentes que originou uma

  17. Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

    Science.gov (United States)

    Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

    2011-11-01

    The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

  18. Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

    Science.gov (United States)

    Barmpalexis, Panagiotis; Grypioti, Agni

    2018-06-01

    This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

  19. Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

    Science.gov (United States)

    Bende, Girish; Biswal, Shibadas; Bhad, Prafulla; Chen, Yuming; Salunke, Atish; Winter, Serge; Wagner, Robert; Sunkara, Gangadhar

    2016-01-01

    The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95-1.00) and 0.85 (0.76-0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00-1.08) and 1.67 (1.43-1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation. © 2015, The American College of Clinical Pharmacology.

  20. A new generation starch product as excipient in pharmaceutical tablets .3. Parameters affecting controlled drug release from tablets based on high surface area retrograded pregelatinized potato starch

    NARCIS (Netherlands)

    TeWierik, GHP; Eissens, AC; ArendsScholte, AW; Bolhuis, GK

    1997-01-01

    This paper describes the general applicability of a new pregelatinized starch product in directly compressible controlled-release matrix systems. It was prepared by enzymatic degradation of potato starch followed by precipitation (retrogradation), filtration and washing with ethanol. The advantages

  1. Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

    Directory of Open Access Journals (Sweden)

    Nnamani PO

    2016-11-01

    Full Text Available Petra Obioma Nnamani,1,2 Agatha Adaora Ugwu,1 Emmanuel Chinedu Ibezim,1 Franklin Chimaobi Kenechukwu,1 Paul Achile Akpa,1 John-Dike Nwabueze Ogbonna,1 Nicholas Chinedu Obitte,3 Amelia Ngozi Odo,4 Maike Windbergs,2 Claus-Michael Lehr,2,5,6 Anthony Amaechi Attama1 1Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria; 2Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS, Helmholtz Centre for Infection Research, Saarland University, Saarbrücken, Germany; 3Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, 4Department of Human Kinetics and Health Education, University of Nigeria, Nsukka, Nigeria; 5PharmBioTec GmbH, 6Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany Abstract: The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL from a nanostructured lipid carrier (NLC of lumefantrine (LUM and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65. Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage

  2. APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

    Science.gov (United States)

    Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

    2016-06-01

    APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

  3. Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit L 100-55.

    Science.gov (United States)

    Sauer, Dorothea; Watts, Alan B; Coots, Lonique B; Zheng, Weijia C; McGinity, James W

    2009-02-09

    The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder-coated with pre-plasticized Eudragit L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit E PO or Eudragit RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel K4M were incorporated in both Eudragit E PO and Eudragit RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel K4M in the film coating was correlated with their ability to function as pore forming agent.

  4. Development and Characterization of Chitosan Cross-Linked With Tripolyphosphate as a Sustained Release Agent in Tablets, Part I: Design of Experiments and Optimization.

    Science.gov (United States)

    Pinto, Colin A; Saripella, Kalyan K; Loka, Nikhil C; Neau, Steven H

    2018-04-01

    Certain issues with the use of particles of chitosan (Ch) cross-linked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages of drug addition extragranularly over drug addition made during cross-linking. The influences of Ch concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and 2-factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets. Statistical model equations directed production of a control batch that minimized span, maximized yield, and targeted a t 50 of 90 min (sample A); sample B that differed by targeting a t 50 of 240-300 min to provide sustained release; and sample C that differed from sample B by maximizing span. Sample B maximized yield and provided its targeted t 50 and the smallest average particle size, with the higher zeta potential and the lower span of samples B and C. Extragranular addition of a drug to Ch:TPP particles achieved 100% drug loading, eliminated a burst drug release, and can accomplish complete drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. A new approach combining different MRI methods to provide detailed view on 2 swelling dynamics of xanthan tablets influencing drug release at different pH and 3 ionic strength

    OpenAIRE

    Sepe, Ana; Mikac, Urška; Baumgartner, Saša; Kristl, Julijana

    2015-01-01

    The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. We have selected magnetic resonance imaging (MRI) as the method of choice for visualizing the dynamic processes occurring during the swelling of xanthan tablets in a variety of media. The aims were (i) to develop a new method using MRI for accurate determination of penetration, swelling and erosion fronts, (ii) to investigate the...

  6. Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

    Science.gov (United States)

    Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

    2015-01-01

    Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (Pmarketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

  7. The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

    Science.gov (United States)

    Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

    2016-03-01

    Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

  8. Evaluation of a Novel, Natural Locust Bean Gum as a Sustained Release and Mucoadhesive Component of Tizanidine Hcl Buccal Tablets

    OpenAIRE

    Harikrishnan.V

    2015-01-01

    Mucoadhesive polymers that bind to the gastric mucin or epithelial cell surface are useful in drug delivery for the purpose of increasing the intimacy and duration of contact of drug with the absorbing membrane. Mainly synthetic polymers are in use for this purpose. Probably the biodegradability of the synthetic polymers are questionable, In the present work mucoadhesive buccal tablets of Tizanidine hydrochloride (TZD HCl) were prepared by using locust bean gum that have better mucoadhesive p...

  9. Development and Evaluation of Mucoadhesive Chlorhexidine Tablet ...

    African Journals Online (AJOL)

    Purpose: To formulate mucoadhesive chlorhexidine tablets and evaluate their drug release characteristics and mechanism. Methods: Chlorhexidine buccal adhesive tablets were prepared by direct compression using a blend of hydroxypropyl methylcellulose (HPMC) and chitosan as the bioadhesive polymers.

  10. Assessing gastrointestinal motility and disintegration profiles of magnetic tablets by a novel magnetic imaging device and gamma scintigraphy.

    Science.gov (United States)

    Goodman, Kirsteen; Hodges, Lee Ann; Band, Janet; Stevens, Howard N E; Weitschies, Werner; Wilson, Clive G

    2010-01-01

    To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study with the following arms: (a) immediate-release tablets administered in fasted state; (b) immediate-release tablets administered after 400mL of Clinutren ISO; (c) enteric-coated tablets administered in the fasted state; and (d) non-disintegrating tablets studied in the lightly fed state (100mL of Clinutren ISO). In both the in vitro and in vivo studies, tablets were detected successfully by MMI and scintigraphy. There was a good correlation between gastric residence times and positional data (in the x, y and y, z-axes). In addition, MMI revealed early swelling behaviour of the tablet matrix. There was excellent agreement for the disintegration times of MT(A) in the fasted arm (scintigraphy 12.0+/-4.4min, MMI 11.8+/-4.4min). In the MT(A)-fed arm, onset times determined by scintigraphy were delayed in three subjects when compared to the corresponding MMI results. Delayed disintegration was observed with MT(A) administered after food (pdisintegration of a magnetic tablet through the gastrointestinal tract. Copyright 2009 Elsevier B.V. All rights reserved.

  11. Evaluating the effect of coating equipment on tablet film quality using terahertz pulsed imaging

    DEFF Research Database (Denmark)

    Haaser, Miriam; Naelapaa, Kaisa; Gordon, Keith C

    2013-01-01

    In this study, terahertz pulsed imaging (TPI) was employed to investigate the effect of the coating equipment (fluid bed and drum coater) on the structure of the applied film coating and subsequent dissolution behaviour. Six tablets from every batch coated with the same delayed release coating fo...

  12. The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release.

    Science.gov (United States)

    Mikac, Urša; Sepe, Ana; Baumgartner, Saša; Kristl, Julijana

    2016-03-07

    The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, μ ≥ 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful.

  13. Highly Sensitive Micellar Enhanced Spectrofluorimetric Method for Determination of Mirtazapine in Tablets and Human Urine: Application to In Vitro Drug Release and Content Uniformity Test

    Directory of Open Access Journals (Sweden)

    Hany W. Darwish

    2016-01-01

    Full Text Available A highly sensitive and simple micelle enhanced spectrofluorimetric method was developed for assaying mirtazapine (MRZ in REMERON® tablets and spiked human urine directly without the need of derivatizing agent. The basis of the current procedure is the examination of the relative fluorescence intensity (RFI of MRZ in sodium lauryl sulphate (SLS micellar medium. The RFI of MRZ in water was enhanced markedly on addition of SLS. The RFI was measured at 403 nm after excitation at 320 nm. The fluorescence-concentration relationship was linear over the range 1–500 ng/mL, with lower detection limit of 0.399 ng/mL. The proposed method was successfully applied to the determination of MRZ in dosage form and spiked human urine. Recovery percentages of MRZ utilizing the current method were 99.05±1.83, 98.37±1.96, and 100.41±2.61% for pure powder, pharmaceutical dosage form, and spiked human urine, respectively. The application of the proposed method was extended to test content uniformity and the in vitro drug release of REMERON tablets, according to USP guidelines.

  14. A Simple and Improved HPLC-PDA Method for Simultaneous Estimation of Fexofenadine and Pseudoephedrine in Extended Release Tablets by Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Ruhul Kayesh

    2017-01-01

    Full Text Available A simple RP-HPLC method has been developed for simultaneous estimation of fexofenadine and pseudoephedrine in their extended release tablet. The method was developed based on statistical design of experiments (DoE and Response Surface Methodology. Separation was achieved on double end-capped C18 column (250 mm × 4 mm, 5 μm. In this experiment, two components of mobile phase, namely, acetonitrile (% v/v and methanol (% v/v, were the factors whereas retention and resolution of the chromatographic peaks were the responses. The effects of different composition of factors on the corresponding responses were investigated. The optimum chromatographic condition for the current case was found as an isocratic mobile phase consisting of 20 mM phosphate buffer (pH 6.8 and acetonitrile and methanol in a ratio of 50 : 36 : 14 (% v/v at a flow rate of 1 mL/min for 7 minutes. The retention of pseudoephedrine and fexofenadine was found to be 2.6 min and 4.7 min, respectively. The method was validated according to the ICH and FDA guidelines and various validation parameters were determined. Also, forced degradation studies in acid, base, oxidation, and reduction media and in thermal condition were performed to establish specificity and stability-indicating property of this method. Practical applicability of this method was checked in extended release tablets available in Bangladeshi market.

  15. Effect of drug content and agglomerate size on tabletability and drug release characteristics of bromhexine hydrochloridetalc agglomerates prepared by crystallo-co-agglomeration.

    Science.gov (United States)

    Jadhav, Namdeo; Pawar, Atmaram; Paradkar, Anant

    2010-03-01

    The objective of the investigation was to study the effect of bromhexine hydrochloride (BXH) content and agglomerate size on mechanical, compressional and drug release properties of agglomerates prepared by crystallo-co-agglomeration (CCA). Studies on optimized batches of agglomerates (BXT1 and BXT2) prepared by CCA have showed adequate sphericity and strength required for efficient tabletting. Trend of strength reduction with a decrease in the size of agglomerates was noted for both batches, irrespective of drug loading. However, an increase in mean yield pressure (14.189 to 19.481) with an increase in size was observed for BXT2 having BXH-talc (1:15.7). Surprisingly, improvement in tensile strength was demonstrated by compacts prepared from BXT2, due to high BXH load, whereas BXT1, having a low amount of BXH (BXH-talc, 1:24), showed low tensile strength. Consequently, increased tensile strength was reflected in extended drug release from BXT2 compacts (Higuchi model, R(2) = 0.9506 to 0.9981). Thus, it can be concluded that interparticulate bridges formed by BXH and agglomerate size affect their mechanical, compressional and drug release properties.

  16. A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes.

    Science.gov (United States)

    Kushner, Joseph; Langdon, Beth A; Hicks, Ian; Song, Daniel; Li, Fasheng; Kathiria, Lalji; Kane, Anil; Ranade, Gautam; Agarwal, Kam

    2014-02-01

    The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity 1 MPa, friability ≤ 0.2% weight loss, and disintegration time impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    Wadher, K. J.; Kakde, R. B.; Umekar, M. J.

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  18. Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

    Science.gov (United States)

    Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

    2004-07-01

    The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

  19. Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

    Science.gov (United States)

    Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

    2015-09-01

    Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets

    OpenAIRE

    Devjak Novak, Sabina; Šporar, Elena; Vrečer, Franc; Baumgartner, Saša

    2015-01-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by differentb manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of act...

  1. Stabilization Mechanism of Roxithromycin Tablets under Gastric pH Conditions.

    Science.gov (United States)

    Inukai, Koki; Noguchi, Shuji; Kimura, Shin-Ichiro; Itai, Shigeru; Iwao, Yasunori

    2018-05-31

    Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of three widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A (EM), and azithromycin (AZM). The results indicated that not only CAM but also RXM gelated under acidic conditions. EM and AZM did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that two of the four macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides. Copyright © 2018. Published by Elsevier Inc.

  2. Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

    Directory of Open Access Journals (Sweden)

    Sylvester Okhuelegbe Eraga

    2015-09-01

    Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specifications. The t50% value of the 1:4 batch of tablets may find its usefulness in formulating drugs for which a fast onset of action is desired.

  3. Effect of gel formation on the dissolution behavior of clarithromycin tablets.

    Science.gov (United States)

    Inukai, Koki; Takiyama, Kei; Noguchi, Shuji; Iwao, Yasunori; Itai, Shigeru

    2017-04-15

    Clarithromycin (CAM) is a macrolide antibiotic that is widely used at clinical sites. We found that release of CAM is suppressed when tablets of CAM were exposed to an external solvent containing carboxylate buffers such as citrate. The suppressed release of CAM can be attributed to the formation of gels on the tablet surfaces, which inhibits penetration of the solvent into the tablet and thus disintegration of the tablets. Delayed disintegration of the tablets was also observed for commercial tablets. This suggests that taking CAM and carboxylates at the same time might be avoided. The crystal structure of CAM citrate reveals that molecular chains of CAM are cross-linked by hydrogen bond between citrate groups in the crystal. The crystal structure indicates that cross-linked CAM chains of the three-dimensional mesh structure might also be formed in high concentration CAM solutions in the presence of carboxylates, resulting in gel formation. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  5. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  6. The Formulation of Diclofenac Sodium Hydrogel Tablets | Onyechi ...

    African Journals Online (AJOL)

    The dissolution data fitted to Higuchi and Hixson-Crowell equations indicating the existence of diffusion mechanism controlling diclofenac release from the tablets. Keywords: Sustained release, diclofenac sodium hydrogel tablets, Voltarol retard tablets, film coating, dissolution profiles. Nigerian Journal of Pharmaceutical ...

  7. Effect of axial diffusional delays on the overall fission gas release

    International Nuclear Information System (INIS)

    Pedersen, N.K.

    1983-01-01

    In fission gas release modeling, it is normally assumed that any locally released gas mixes instantly and perfectly with other gases throughout the internal rod void volume. The present work investigates the consequences of the assumption that perfect mixing is dependent on diffusion, although the subassumption is maintained that pressure equilibrium is instantly achieved. In other words, when a burst of gas release occurs at any axial location, sufficient local accommodation takes place throughout the rod to eliminate any pressure gradients, but due to the narrowness of the passages through fuel cracks and fuel-cladding gap, concentration gradients may still prevail. Diffusion coefficients for the subsequent concentration equilibration are derived from classical theories. Application of one-dimensional diffusion theory is straightforward, but the lack of knowledge of the effective width of the axial passage introduces an uncertainty

  8. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  9. Quality of Life is Improved and Kidney Function Preserved in Patients with Nephropathic Cystinosis Treated for 2 Years with Delayed-Release Cysteamine Bitartrate

    NARCIS (Netherlands)

    Langman, C.B.; Greenbaum, L.A.; Grimm, P.; Sarwal, M.; Niaudet, P.; Deschenes, G.; Cornelissen, E.A.M.; Morin, D.; Cochat, P.; Elenberg, E.; Hanna, C.; Gaillard, S.; Bagger, M.J.; Rioux, P.

    2014-01-01

    OBJECTIVES: To determine the long-term effects of delayed-release cysteamine bitartrate (DR-CYS) based on our previous work that established the short-term noninferiority of DR-CYS every 12 hours compared with immediate-release cysteamine bitartrate every 6 hours. STUDY DESIGN: We conducted a

  10. Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests.

    Science.gov (United States)

    Mamani, Pseidy L; Ruiz-Caro, Roberto; Veiga, María D

    2012-12-01

    Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7 h) and a total drug delivery in 17 h in simulated colonic fluid.

  11. Efeito da concentração do amido de milho na liberação de paracetamol de comprimidos Effect of maize starch concentration on in vitro acetaminophen release from tablets

    Directory of Open Access Journals (Sweden)

    Ana Dóris de Castro

    2003-09-01

    Full Text Available Este trabalho avaliou a influência da concentração de amido de milho nas características físicas e na liberação in vitro de paracetamol a partir de comprimidos. Os granulados foram analisados quanto à granulometria e densidades aparentes bruta e compactada e os comprimidos quanto ao peso médio, espessura, dureza, friabilidade, tempo de desintegração. Os comprimidos foram preparados a partir de granulados obtidos por granulação a úmido, utilizando cozimento de amido a 10% como agente granulante, segundo três formulações. Embora os comprimidos obtidos tenham apresentado características dentro dos limites farmacopéicos, os resultados indicam que variações da concentração de amido provocam diferenças nos diversos parâmetros físicos estudados. Concentração mais alta de amido em pó dá origem, provavelmente, à interação entre os componentes da fórmula, interferindo na liberação in vitro do fármaco. Isto demonstra a importância de se otimizar a concentração dos adjuvantes numa formulação de comprimidos, pois, embora uma pequena variação nesta concentração não exerça efeito significativo no tempo de desintegração, a quantidade de fármaco liberado pode ser substancialmente alterada.This paper describes the influence of maize starch concentration on the physical characteristics and on in vitro release of acetaminophen from compressed tablets. The granulates were analyzed in relation to size distribution and bulk and compacted densities, and the tablets in relation to mean weight, thickness, hardness, friability and disintegration time. The tablets were prepared from granulates made by wet granulation with 10% starch paste in three formulations. Although the tablets obtained have presented characteristics in accordance with pharmacopeial limits, the results indicate that variations on starch concentration cause differences on the several physical parameters studied. Higher starch concentration probably

  12. Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Eric T Wittbrodt

    2009-11-01

    Full Text Available Eric T Wittbrodt1, Charles Baum2, David A Peura31Takeda Pharmaceuticals North America, Inc., 2Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA; 3University of Virginia, School of Medicine, Charlottesville, VA, USAAbstract: Although proton pump inhibitors (PPI have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD, several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional singlerelease PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods vs placebo (14% for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.Keywords: dexlansoprazole MR, gastroesophageal reflux disease, GERD, erosive esophagitis, TAK-390MR

  13. Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

    Science.gov (United States)

    Hognert, Helena; Kopp Kallner, Helena; Cameron, Sharon; Nyrelli, Christina; Jawad, Izabella; Heller, Rebecca; Aronsson, Annette; Lindh, Ingela; Benson, Lina; Gemzell-Danielsson, Kristina

    2016-11-01

    Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion

  14. Double-layer Tablets of Lornoxicam: Validation of Quantification ...

    African Journals Online (AJOL)

    Double-layer Tablets of Lornoxicam: Validation of Quantification Method, In vitro Dissolution and Kinetic Modelling. ... Satisfactory results were obtained from all the tablet formulations met compendial requirements. The slowest drug release rate was obtained with tablet cores based on PVP K90 (1.21 mg%.h-1).

  15. Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

    Science.gov (United States)

    Sun, Changquan Calvin

    2017-05-01

    To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

  16. Tablet telerounding.

    Science.gov (United States)

    Kaczmarek, Bartosz F; Trinh, Quoc-Dien; Menon, Mani; Rogers, Craig G

    2012-12-01

    To evaluate the feasibility of remote rounding using commercially available standard tablets with videoconferencing system and assess patient satisfaction. Thirty-two patients with at least 2 postoperative days of hospital stay after robotic urologic procedures were included in the study. On the first postoperative day, the physician-patient encounter was performed as telerounding with videoconferencing due to the physician's duties scheduled in another affiliated hospital. On the second day, the personal bedside encounter took place. The tablet we used was an iPad2 (Apple, iOS 5.1; Apple, Cupertino, CA) with a videoconferencing application. A telerounding satisfaction survey was fulfilled by all patients on the touchscreen of the tablet. Average time of telerounding encounter was 4.5 minutes (range, 1.0-13.5 minutes), average age of the patient was 57.7 years (range, 19-80 years), and 19 were men (59%). Patients expressed a high level of satisfaction with 91% of patients stating that their care was better using telerounding and 97% of patients stating that telerounding should be a regular part of patient care in the hospital. Additionally, 94% of patients stated that they could easily communicate with their doctor over the telerounding system, 84% of patients agreed that they would feel comfortable with telerounding daily if they were hospitalized again and 81% of patients would prefer telerounding communication with their doctor than be directly seen by another doctor. Tablet telerounding using videoconferencing can be a strong supplementing tool in doctor-patient communication. It is convenient for the physician and increases the patient's hospital stay satisfaction. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Pharmacokinetic Studies on Metoprolol - Eudragit Matrix Tablets ...

    African Journals Online (AJOL)

    HP

    Zero order release of drug was observed from all the tablets. ... Conclusion: It can be concluded from this single-dose study that the reference and test ... effect [2]. The mean time to reach maximum plasma concentration and mean elimination.

  18. Effect of food on the pharmacokinetic properties of the oral sarpogrelate hydrochloride controlled-release tablet in healthy male Korean subjects.

    Science.gov (United States)

    Jung, Jin Ah; Kim, Jung-Ryul; Kim, Tae-Eun; Lee, Soo-Youn; Huh, Wooseong; Lee, Jae Won; Jun, Hun; Ko, Jae-Wook

    2013-07-01

    A new controlled-release formulation of sarpogrelate, a 5-hydroxytryptamine receptor subtype 2 antagonist that blocks serotonin-induced platelet aggregation, has been developed for once-daily administration. This study evaluated the effect of food on the pharmacokinetic properties of controlled-release sarpogrelate (sarpogrelate CR) in healthy volunteers. A randomized, open-label, two-period, two-treatment crossover study was performed in healthy male Korean subjects. Following an overnight fast, a single dose of sarpogrelate CR 300 mg was administered either in the fasted condition or immediately after a high-fat breakfast. Pharmacokinetic parameters were calculated using a noncompartmental analysis. Tolerability was determined using clinical laboratory testing and physical examination, including vital sign measurements, electrocardiography, and interviews with the volunteers regarding adverse events (AEs). A total of 24 healthy subjects were enrolled, 23 of whom completed the study (mean [range] age, 26 years [21-45]; weight, 68.1 kg [56.0-79.9]; body mass index, 22.1 kg/m(2) [18.8-25.0]). Sarpogrelate C(max) and AUC(last) were decreased In the fed condition compared with those in the fasted condition, with geometric mean ratios (90% CI) of 0.4868 (0.4041-0.5864) and 0.7394 (0.6809-0.8028), respectively. T(max) was delayed from 0.75 to 4.0 hours after a high-fat meal, but the fed condition exhibited a similar elimination profile to that of the fasted condition. The most commonly reported AE was headache (n = 2), and other AEs were reported in 1 subject each. All of the AEs were considered mild in intensity, and the participants recovered without treatment. Compared with the administration of sarpogrelate CR 300 mg in the fasted condition, administration with food was associated with a decreased rate and extent of absorption, as assessed by C(max) and AUC(last), respectively. The drug was well-tolerated by the healthy subjects in this study. Copyright © 2013

  19. Desarrollo tecnológico y estudio de estabilidad de tabletas de liberación inmediata de meprobamato Technological development and stability study of meprobamate immediate released tablets

    Directory of Open Access Journals (Sweden)

    Mirna Fernández Cervera

    2010-12-01

    Full Text Available Se estudió el comportamiento de diferentes variantes tecnológicas de tabletas de liberación inmediata de meprobamato (400 mg, obtenidas por granulación húmeda. El tiempo de desintegración y el porcentaje de fármaco disuelto mostraron dependencia significativa con las proporciones del lauril sulfato de sodio/croscarmelosa sódica en las formulaciones. Se evaluaron las propiedades físicas y químicas de las tabletas durante 6 meses (estabilidad acelerada y 24 meses (de vida útil, respectivamente. Se obtuvieron a partir de las formulaciones seleccionadas granulados y tabletas con propiedades organolépticas, físico-mecánicas y tecnológicas satisfactorias, lo que indicó la factibilidad del proceso de fabricación de este producto. Los resultados demostraron la buena estabilidad de las formulaciones de tabletas de liberación inmediata de meprobamato seleccionadas. La disolución in vitro no mostró diferencias significativas, por lo que ni el tiempo transcurrido ni la composición de la formulación influyeron sobre los porcentajes del fármaco disuelto. La valoración mostró diferencias significativas, sin embargo, las formulaciones evaluadas cumplieron con las especificaciones farmacéuticas oficiales durante 24 meses.The behavior of different technological variants of fast release tablets of Meprobamato (400 mg obtained by wet granulation. The desintegration time and the percentage of the dissolved drug showed a significant dependence of the sodium lauryl sulfate /sodium croscarmelose ratios present in formulae. The physical and chemical properties of tablets were assessed during 6 months (accelerated stability and dring 24 months (useful life, respectively. From the formulae selected it was possible to obtain granulates and tablets with organoleptic, physicomechanical and technological properties, demonstrating the feasibility of the process of fabrication of this product. Results showed the good stability in the immediate release

  20. 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.

  1. The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

    Science.gov (United States)

    Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

    2015-01-01

    Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

  2. Optimization and Formulation of Orodispersible Tablets of Meloxicam

    African Journals Online (AJOL)

    ... 98.5% and fast drug release rate of 99.5% within 30 min, as compared with the conventional tablet (49.5%) . Conclusion: It is feasible to formulate orodispersible tablets of meloxican with acceptable disintegration time, rapid drug release and good hardness, which could be amenable to replication on an industrial scale.

  3. Tablet Use within Medicine

    Science.gov (United States)

    Hogue, Rebecca J.

    2013-01-01

    This paper discusses the scholarly literature related to tablet computer use in medicine. Forty-four research-based articles were examined for emerging categories and themes. The most studied uses for tablet computers include: patients using tablets to complete diagnostic survey instruments, medical professionals using tablet computers to view…

  4. An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

    2015-04-30

    Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Stress degradation studies of Telmisartan and Metoprolol extended release tablets by a validated stability indicating reverse phase-high performance liquid chromatography method

    Directory of Open Access Journals (Sweden)

    Kabeer Ahmed Shaikh

    2014-01-01

    Full Text Available Background and Aim: A sensitive reverse phase high-performance liquid chromatographic method has been developed for the simultaneous determination of Telimisartan and Metoprolol in tablet dosage form. Materials and Method: The chromatographic separation was achieved on Inertsil ODS 3V, 150 x 4.6 mm, 5μ analytical column. Mobile phase consisting of mobile phase A- 0.05M sodium dihydrogen phosphate buffer pH 3.0 and mobile phase B-Acetonitrile, with gradient program time in min /Mobile phase B% 0/22, 4/45, 6/45,18/22, 20/22. Detector was set at 222nm. Results and Conclusion: The described method shows excellent linearity over a range of 80-2 μg mL−1 for Telmisartan and 100-4 μg mL−1 for Metoprolol. The correlation coefficient for Telmisartan is 0.9998 and Metoprolol is 0.9999. The proposed method was found to be suitable for determination of Telmisartan and Metoprolol in tablet dosage form. Forced degradation of the drug product was conducted in accordance with the ICH guideline. Acidic, basic, hydrolytic, oxidative, thermal and photolytic degradation was used to assess the stability indicating power of the method. The drug product was found to be stable in acid, oxidation, thermal and photolytic stress condition and found degradation in base hydrolysis stress condition.

  6. Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

    Science.gov (United States)

    Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

    2018-06-14

    Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

  7. 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

  8. Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial

    Directory of Open Access Journals (Sweden)

    Isbel Nicole M

    2009-07-01

    Full Text Available Abstract Background The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin® ES administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA-treated peritoneal dialysis (PD patients than conventional oral iron supplementation (Ferrogradumet®. Methods Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp®, Amgen for ≥ 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control or HIP (1 tablet twice daily for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA. Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration, and occurrence of adverse events (especially gastrointestinal adverse events. Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. Trial Registration Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

  9. Effect of Coating Solvent Ratio on the Drug Release Lag Time of ...

    African Journals Online (AJOL)

    Erah

    Research Article ... Lag Time of Coated Theophylline Osmotic Tablets ... Key words: Coating solvent, Drug release, Lag time, Osmotic tablet, HPMC, .... following composition (w/w): theophylline ... tablets was measured by UV absorption.

  10. [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.

  11. 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.

  12. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, Oli Jacob; Hansen, Niels-Christian Gerner; Søes-Petersen, Ulrik

    2004-01-01

    Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...

  13. Compressibility of tableting materials and properties of tablets with glyceryl behenate

    Directory of Open Access Journals (Sweden)

    Mužíková Jitka

    2015-03-01

    Full Text Available The paper studies the compressibility of directly compressible tableting materials with dry binders, spray-dried lactose and microcrystalline cellulose, and glyceryl dibehenate at various concentrations. Compressibility was evaluated by means of the energy profile of compression and tensile strength of tablets. Release rate of the active ingredient, salicylic acid, from the tablets was also examined. In the case of microcrystalline cellulose, a higher concentration of glyceryl dibehenate increased the strength of tablets, while this did not occur in the case of spray-dried lactose. Increasing concentration of glyceryl dibehenate prolonged the release of salicylic acid; however, no statistically significant difference was found compared to the type of the dry binder used

  14. Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets

    Directory of Open Access Journals (Sweden)

    Rawan A. Fitaihi

    2018-02-01

    Full Text Available Vaginal fluconazole (FLZ prolonged release tablets containing chitosan in physical blends with other bioadhesive polymers were designed. Chitosan was mixed with hydroxypropyl methylcellulose (HPMC, guar gum or sodium carboxymethyl cellulose (NaCMC at different ratios and directly compressed into tablets. In-vitro release profiles of FLZ were monitored at pH 4.8. Compressing chitosan with HPMC at different ratios slowed FLZ release, however, time for 80% drug release (T80 did not exceed 4.3 h for the slowest formulation (F11. Adding of chitosan to guar gum at 1:2 ratio (F3 showed delayed release with T80 17.4 h while, in presence of PVP at 1:2:1 ratio (F5, T80 was 8.8 h. A blend of chitosan and NaCMC at 1:2 ratio (F15 showed prolonged drug release with T80 11.16 h. Formulations F5 and F15 showed fair physical characteristics for the powder and tablets and were subjected to further studies. Fast swelling was observed for F15 that reached 1160.53 ± 13.02% in 4 h with 2 h bioadhesion time to mouse peritoneum membrane compared with 458.83 ± 7.09% swelling with bioadhesion time exceeding 24 h for F5. Extensive swelling of F15 could indicate possible dehydration effect on vaginal mucosa. Meanwhile, antifungal activity against C. albicans was significantly high for F5.

  15. Contamination delays the release of Laricobius osakensis for biological control of hemlock woolly adelgid: cryptic diversity in Japanese Laricobius spp

    Science.gov (United States)

    Melissa J. Fischer; Nathan P. Havill; Carrie S. Jubb; Sean W. Prosser; Brent D. Opell; Scott M. Salom; Loke T. Kok

    2014-01-01

    Laricobius osakensis (Coleoptera: Derodontidae) was imported from Japan to the United States in 2006 for study in quarantine facilities as a potential biological control of Hemlock Woolly Adelgid. Laricobius osakensis was released from quarantine in 2010, but it was soon discovered that the colony also contained a cryptic species...

  16. Delayed Release from Proactive Interference with Meaningful Material: How Much Do We Remember After Reading Brief Prose Passages?

    Science.gov (United States)

    Blumenthal, Gary B.; Robbins, Donald

    1977-01-01

    Three experiments were conducted, investigating the buildup of and the release from proactive interference, in which the stimulus materials were brief prose passages about specific topics. Each passage was followed by a multiple-choice test, and then a final test on all the passages read was given. Implications of the data for standardized tests…

  17. Delayed Effects of Remote Limb Ischemic Preconditioning on Maximum Oxygen Consumption, Lactate Release and Pulmonary Function Tests in Athletes and non-Athletes

    Directory of Open Access Journals (Sweden)

    Mahnaz Momeni

    2016-11-01

    Full Text Available Background: Remote Ischemic Preconditioning (RIPC improves exercise performance, and since this phenomenon has two phases, the aim of the current study was to investigate the delayed effects of remote ischemic preconditioning on cardiopulmonary function in athletes and non-athletes. Materials and Methods: 25 male and female students were studied in two main athletes and non-athletes groups. RIPC was induced by using 3 cycles of alternative 5 minutes ischemia and 5 minutes reperfusion at arms of participants. Cardiopulmonary tests were measured before, after and 24 hours after inducing remote ischemic preconditioning. Maximum oxygen consumption (VO2max estimated by using queen steps test. Results: Analysis of data demonstrated that delayed RIPC in non-athletes group caused significant improvement in Forced Expiratory Volume in one second (FEV1 and Maximum Voluntary Ventilation (MVV and noticeable improvement in some other parameters of pulmonary function tests. Moreover, it decreased systolic blood pressure and heart rate and decreased lactate release in both groups especially athletes group but it had no significant effect on VO2max of both groups. Conclusion: Delayed RIPC improves cardiovascular function of athletes and pulmonary function of non-athletes subjects. Thus, it can be considered as a good replacement for doping to improve sports performance of subjects in sports tournaments.

  18. Evaluation of zero-order controlled release preparations of nifedipine tablet on dissolution test, together with cost benefit point of view.

    Science.gov (United States)

    Sakurai, Miyuki; Naruto, Ikue; Matsuyama, Kenji

    2008-05-01

    Many generic drugs have been released to decrease medical expenses, but some problems have been reported with regard to bioavailability and safety. In this study, we compared three once-a-day controlled-release preparations of nifedipine by the dissolution test (one branded and two generic preparations). Although the two generic drugs were equivalent to the branded drug according to the criteria listed in the Japanese "Guideline for Bioequivalence Studies of Generic Products", there was still a possibility of problems arising. For example, side effects could be caused by a rapid increase in the blood level of nifedipine with one generic drug, while bioavailability might be inadequate with the other due to its small area under the concentration vs. time curve. When each drug was prescribed at a dosage of 20 mg once daily for two weeks, the difference in the copayment for the patient was only 10 yen. Accordingly, it is important for doctors and pharmacists to carefully consider whether such a slight difference in price is really a benefit for the patient.

  19. Evaluation of olibanum and its resin as rate controlling matrix for controlled release of diclofenac

    OpenAIRE

    Chowdary KPR; Mohapatra P; Murali Krishna M

    2006-01-01

    Olibanum and its resin and carbohydrate fractions were evaluated as rate controlling matrix materials in tablets for controlled release of diclofenac. Diclofenac matrix tablets were formulated employing olibanum and its resin and carbohydrate fractions in different concentrations and the tablets were evaluated for various tablet characters including drug release kinetics and mechanism. Olibanum and its resin component exhibited excellent retarding effect on drug release from the matrix tablet...

  20. Assessment of Albizia zygia gum as binding agent in tablet formulations

    OpenAIRE

    ODEKU, OLUWATOYIN A.

    2005-01-01

    Albizia gum has been evaluated as a binding agent in tablet formulations in comparison with gelatin BP. Compressional properties were analyzed using density measurements and the compression equations of Heckel and Kawakita as assessment parameters, while the mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets. Drug release properties of the tablets were assessed using disintegration time and dissolution time as assessment parameters. Fo...

  1. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, O.J.; Gerner Hansen, Niels-Christian; Soes-Petersen, U.

    2004-01-01

    (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking......Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...... more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark....

  2. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2012-01-01

    Full Text Available In this study, we determined the molecular mechanism of γ-tocotrienol (GTT in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs. Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal and promoted G0/G1 cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P<0.05. GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P<0.05. Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05 in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.

  3. Vaccination improves survival of Baltic salmon ( Salmo salar ) smolts in delayed release sea ranching (net-pen period)

    DEFF Research Database (Denmark)

    Buchmann, Kurt; Dalsgaard, Inger; Nielsen, Michael Engelbrecht

    1997-01-01

    Baltic salmon (Salmo salar) of the Finnish Iijoki stock were hatched and reared in freshwater in a salmon hatchery on the Danish island of Bornholm in the Baltic sea. Salmon parr were divided in three groups each comprising 22 000 fish. One group was vaccinated by intraperitoneal injection....... In contrast, no increase of titres was seen in the bath vaccinated and untreated groups. Marked cellular reactions in the abdominal cavity of injected fish were registered. A total of 3000 fish have been tagged and released to evaluate the effect of vaccination on the recapture rate. The implications...

  4. 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 ...

  5. BIOWAIVER STUDY OF ORAL TABLETTED ETHYLCELLULOSE ...

    African Journals Online (AJOL)

    Preferred Customer

    classification of drugs on the basis of their solubility and permeability. ..... velocity of drug release was slower from tablets with low polymer ... when the drug solubility is high, (b) loading dose in the polymeric matrix is large and (c) lack of.

  6. Dissolution and permeation characteristics of artemether tablets ...

    African Journals Online (AJOL)

    characterized by delayed drug release but enhanced permeation of the released drug. Keywords: ... and prosopis gum as binders and to consider the relationship between ..... higher tensile strength and higher brittle fracture index compared ...

  7. Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect.

    Science.gov (United States)

    Sonvico, Fabio; Conti, Chiara; Colombo, Gaia; Buttini, Francesca; Colombo, Paolo; Bettini, Ruggero; Barchielli, Marco; Leoni, Barbara; Loprete, Luca; Rossi, Alessandra

    2017-09-28

    In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effects of telmisartan combined with nifedipine controlled release tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension

    Directory of Open Access Journals (Sweden)

    Feng Guo

    2017-10-01

    Full Text Available Objective: To investigate the effect of telmisartan combined with Nifedipine Controlled Release Tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension. Methods: A total of 92 cases of patients with coronary heart disease with mild to moderate hypertension were selected as the object of observation, according to the random data table, they were divided into the control group (n=46 and observation group (n=46, and patients in the control group were treated with Nifedipine Controlled Release Table therapy, on this basis, the observation group patients were given telmisartan treatment, two groups were treated for 6 months. The levels of the blood pressure, inflammatory factors, vascular endothelial function and left ventricular function compared between the two groups before and after treatment. Results: There were no significant differences in the levels of SBP, DBP, hs-CRP, TNF-α, NO, ET-1, LVEF, LVEDD and LVESD in the two groups before treatment. After treatment, two groups of SBP, DBP, hs-CRP, TNF-α, ET-1, LVEDD and LVESD levels were significantly lower than those in the same group before treatment, and after treatment, the levels of SBP, DBP, hs-CRP, TNF-α, ET-1 and LVESD in the observation group were significantly lower than those in the control group, while there were no significant difference in the level of LVEDD between the two groups after treatment; Compared with level in the group before treatment, the levels of NO and LVEF in the two groups were significantly increased, and the observation group [(82.13±19.01 µmol/L, (52.83±7.45%] was significantly higher than the control group [(67.37±13.08 µmol/L, (49.47±6.96%]. Conclusion: Telmisartan combined with Nifedipine Controlled Release Table in treating coronary heart disease with mild to moderate hypertension, can effectively control blood pressure, reduce the

  9. A TABLET SCREEN CAST RECEIVER FOR CLASSROOM WITH LOW END ANDROID DEVICES

    Directory of Open Access Journals (Sweden)

    Moh. Hasbi Assidiqi

    2016-07-01

    Full Text Available Salah satu aktivitas menggunakan tablet adalah presentasi. Saat ini, kebanyakan aktivitas presentasi dilakukan menggunakan adapter VGA untuk bisa tersambung dengan LCD Proyektor. Konfigurasi ini memungkin presentasi berbasis kabel. Dan ini adalah hal yang menyulitkan penggunaannya untuk perangkat tablet yang memiliki sifat mobilitas tinggi. Beruntung, sudah ada banyak vendor yang menyediakan sistem presentasi yang bersahabat dengan membuatnya menjadi nirkabel. Tapi sistem tersebut hanya mendukung perangkat tablet high end. Pada makalah ini, kami mengajukan sebuah penerima tablet screen cast untuk perangkat tablet android low end. Yang memiliki potensi untuk diimplementasikan di kelas. Dari eksperimen, kami memperoleh hasil 9 FPS dengan delay sebesar 2 detik.

  10. Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

    Science.gov (United States)

    Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

    2018-04-20

    Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

  11. Effect Of Neutron Activation Factor On The Physico-Chemical Properties Of Hydrophilic And Hydrophobic Polymer Formulation Of Matrix Tablets

    International Nuclear Information System (INIS)

    Ibrahim Ijang; Bohari Yaacob; Nordiana, N.R.

    2011-01-01

    This study was to investigate effect of neutron activation on the physicochemical properties and in vitro dissolution of sustained-release matrix tablets. The tablets incorporation of Samarium oxide (Sm 2 O 3 ) and were compared before and after irradiation with thermal neutron for 5 minutes at 1.2 x 10 12 neutron cm -2 s -1 . The neutron activation factor did not influence the compression properties of the tablets. The dissolution tests showed that irradiation increased the release of the model drug ketoprofen from the tablets. This effect might be explained by polymer degradation. Incorporation of Sm 2 O 3 in the matrix tablets did not influence the release. (author)

  12. Using Tablet on Education

    Science.gov (United States)

    Algoufi, Rateeba

    2016-01-01

    Technological advancements in digital devices have made educational methodology to adopt new strategies and procedures to suit the Mobile learning era. Mobile devices such as tablets are growing to be the focus of research studies and educational use around the globe in the present day. With the influence of handy computing tablets in the hands of…

  13. Ghost tablet in feces.

    Science.gov (United States)

    Iwamuro, Masaya; Morishita, Yosuke; Urata, Haruo; Okada, Hiroyuki

    2017-12-01

    Recently, we encountered a female patient who identified the presence of a ghost tablet in her fecal matter. Interestingly, although the patient was prescribed potassium chloride capsules, elemental composition analysis by energy-dispersive X-ray spectroscopy was unable to detect the presence of either potassium or chloride in the fecal tablet remnant.

  14. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

    Science.gov (United States)

    Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

    2018-05-01

    Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

  15. Absorption from iron tablets given with different types of meals.

    Science.gov (United States)

    Hallberg, L; Björn-Rasmussen, E; Ekenved, G; Garby, L; Rossander, L; Pleehachinda, R; Suwanik, R; Arvidsson, B

    1978-09-01

    The absorption of iron from tablets given with 5 types of meals was studied in 153 subjects. The meals were: a hamburger meal with beans and potatoes, a simple breakfast meal, a Latin American meal composed of black beans, rice and maize and two Southeast Asian meals composed of rice, vegetables and spices served with and without fish. The groups were directly compared by relating the absorption from the iron tablets to the absorption from a standardized reference dose of iron given on an empty stomach. The composition of meals with respect to content of meat or fish or the presence of large amounts of phytates seemed to have no influence on the absorption of iron from tablets. The absorption from iron tablets was about 40% higher when they were given with rice meals than when they were given with the other meals studied. The average decrease in absorption by meals was about 50-60% based on a comparison when tablets were given on an empty stomach. When tablets from which the iron was released more slowly were used, the absorption increased by about 30% except when they were given with rice meals, where the absorption was unchanged. The differences among the meals in their effect on the absorption of iron from tablets thus disappeared when the slow-release tablets were given.

  16. Absorption from iron tablets given with different types of meals

    Energy Technology Data Exchange (ETDEWEB)

    Hallberg, L; Bjoern-Rasmussen, E; Ekenved, G; Garby, L; Rossander, L; Pleehachinda, R; Suwanik, R; Arvidsson, B

    1978-01-01

    The absorption from iron tablets given with 5 types of meals was studied in 153 subjects. The meals were: a hamburger meal with beans and potatoes, a simple breakfast meal, a Latin American meal composed of black beans, rice and maize and two Southeast Asian meals composed of rice, vegetables, and spices served with and without fish. The groups were directly compared by relating the absorption from the iron tablets to the absorption from a standardized reference dose of iron given on an empty stomach. The composition of meals with respect to content of meat or fish or the presence of large amounts of phytates seemed to have no influence on the absorption of iron from tablets. The absorption from iron tablets was about 40% higher when they were given with rice meals than when they were given with the other meals studied. The average decrease in absorption by meals was about 50-60% based on a comparison when tablets were given on an empty stomach. When tablets from which the iron was released more slowly were used, the absorption increased by about 30% except when they were given with rice meals, where the absorption was unchanged. The differences among the meals in their effect on the absorption of iron from tablets thus disappeared when the slow-release tablets were given.

  17. Absorption from iron tablets given with different types of meals

    International Nuclear Information System (INIS)

    Hallberg, L.; Bjoern-Rasmussen, E.; Ekenved, G.; Garby, L.; Rossander, L.; Pleehachinda, R.; Suwanik, R.; Arvidsson, B.

    1978-01-01

    The absorption from iron tablets given with 5 types of meals was studied in 153 subjects. The meals were: a hamburger meal with beans and potatoes, a simple breakfast meal, a Latin American meal composed of black beans, rice and maize and two Southeast Asian meals composed of rice, vegetables, and spices served with and without fish. The groups were directly compared by relating the absorption from the iron tablets to the absorption from a standardized reference dose of iron given on an empty stomach. The composition of meals with respect to content of meat or fish or the presence of large amounts of phytates seemed to have no influence on the absorption of iron from tablets. The absorption from iron tablets was about 40% higher when they were given with rice meals than when they were given with the other meals studied. The average decrease in absorption by meals was about 50-60% based on a comparison when tablets were given on an empty stomach. When tablets from which the iron was released more slowly were used, the absorption increased by about 30% except when they were given with rice meals, where the absorption was unchanged. The differences among the meals in their effect on the absorption of iron from tablets thus disappeared when the slow-release tablets were given. (author)

  18. Optical and terahertz measurement techniques for flat-faced pharmaceutical tablets: a case study of gloss, surface roughness and bulk properties of starch acetate tablets

    International Nuclear Information System (INIS)

    Juuti, M; Tuononen, H; Kontturi, V; Peiponen, K-E; Prykäri, T; Alarousu, E; Myllylä, R; Kuosmanen, M; Ketolainen, J

    2009-01-01

    Surface and bulk properties of flat-faced starch acetate tablets were studied. For surface quality inspection optical coherence tomography and recently developed diffractive glossmeter were utilized. Both these optical devices together provide local information on surface roughness and gloss of a tablet over a measured area. The concepts of mean topography and mean gloss profile for surface quality of a tablet are introduced. It was observed that the surface quality of the tablet varies, and compression at high pressure may not guarantee a good surface quality of the tablet. Using novel statistical parameters for gloss and relevant surface roughness parameter, it is possible to get more comprehensive quantitative data on the surface condition of a tablet. THz spectrometer was utilized for detection of THz pulse delay in transmission measurement mode from the tablets. The delay time and thickness ratio of the tablet are consistent with the porosity of the tablet as a function of compression pressure. We suggest that the multimeasurement scheme using three different devices helps tablet makers to better assess bulk and surface quality of their products

  19. Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study.

    Science.gov (United States)

    Vicariotto, Franco; Mogna, Luca; Del Piano, Mario

    2014-01-01

    Bacterial vaginosis (BV) is the most common reason for abnormal vaginal discharge in reproductive-age women and one of its most important causative agents is the gram-variable bacterium Gardnerella vaginalis. BV is not accompanied by significant local inflammation, whereas the "fishy odor" test is always positive. In contrast, aerobic vaginitis (AV) is predominantly associated with Escherichia coli, but Streptococcus agalactiae and Staphylococcus aureus are also involved. Standard treatment of BV consists of oral or intravaginal antibiotics, although these are unable to spontaneously restore normal flora characterized by a high concentration of lactobacilli. The main limitation is the inability to offer a long-term defensive barrier, thus facilitating relapses and recurrences. This study was undertaken firstly to assess the ability of selected lactobacilli to in vitro antagonize G. vaginalis to determine an association with a strain able to inhibit E. coli, thus identifying a possible use in AV. The second step of the study was to conduct a human pilot trial in women affected by BV using an association of the most promising and active bacteria. For this purpose, neutralized supernatants of individual lactobacilli were tested at percentages ranging from 0.5% to 4% to determine their ability to hinder the growth of G. vaginalis American Type Culture Collection 10231. The bacterium that was able to exert the strongest inhibition was subsequently tested with Lactobacillus plantarum LP01 in a human intervention, placebo-controlled, pilot trial involving 34 female subjects (aged between 18 and 50, mean 34.7±8.9, no menopausal women) diagnosed with BV. The 2 microorganisms Lactobacillus fermentum LF15 (DSM 26955) and L. plantarum LP01 (LMG P-21021) were delivered to the vagina by means of slow-release vaginal tablets, also containing 50 mg of tara gum. The amount of each strain was 400 million live cells per dose. The women were instructed to apply a vaginal tablet once

  20. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2015-09-01

    Full Text Available Martin E Hale,1 Charles Laudadio,2 Ronghua Yang,2 Arvind Narayana,2 Richard Malamut2 1Gold Coast Research, LLC, Plantation, FL, 2Teva Branded Pharmaceutical Products R & D, Inc., Frazer, PA, USA Abstract: This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable. Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148 or hydrocodone ER (n=146. Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134; although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, –0.20 vs 0.40; P=0.032. Significantly more patients had .33% and .50% increase in weekly API with placebo (P<0.05, and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026. Supplemental medication usage was higher with placebo (86% than hydrocodone ER (79%. Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or

  1. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain.

    Science.gov (United States)

    Lee, Jae Hyup; Lee, Chong-Suh

    2013-11-01

    Chronic low back pain is a common condition that is often difficult to treat. The combination of tramadol hydrochloride and acetaminophen in an extended-release formulation has been shown to provide rapid and long-lasting analgesic effects resulting from the synergistic activity of these 2 active ingredients. The goal of this study was to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain. This Phase III, double-blind, placebo-controlled, parallel-group study enrolled 245 patients with moderate to severe (≥4 cm on a 10-cm visual analog scale) chronic (≥3 months') low back pain insufficiently controlled by previous NSAIDs or cyclooxygenase-2-selective inhibitors and randomly assigned them to receive 4 weeks of either TA-ER or placebo. The primary efficacy end point was the percentage of patients with a pain intensity change rate ≥30% from baseline to final evaluation. Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events. The percentage of patients with a pain intensity change rate ≥30% was significantly higher (P Pain relief success rate from baseline was significantly higher with TA-ER versus placebo at days 8 and 15 but not at the final visit. Patients in the TA-ER group had significant improvements versus placebo in role-physical, general health, and reported health transition domains of the Korean Short Form-36 and significantly higher functional improvements in the personal care section of the Korean Oswestry Disability Index. Patient assessment of overall pain control as "very good" was also significantly higher with TA-ER than with placebo. Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting. TA-ER was significantly more

  2. Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption - pH-dependent absorption of metoprolol from bioadhesive tablets.

    Science.gov (United States)

    Meng-Lund, Emil; Jacobsen, Jette; Andersen, Morten B; Jespersen, Mads L; Karlsson, Jens-Jacob; Garmer, Mats; Jørgensen, Erling B; Holm, René

    2014-05-01

    The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.

  3. Iodine tablets and a nuclear accident

    International Nuclear Information System (INIS)

    Paile, W.

    1992-01-01

    Radioactive iodine is one of the major substances released during severe nuclear accidents. Radioactive iodine is easily gasified, and if present in fallout it can enter the lungs, and thereby the circulatory system, with the inhalation of air. Once in a body, radioactive iodine accumulates in the thyroid and may result in tumours in the thyroid and, in extreme cases, impaired thyroid function. Accumulation of radioactive iodine can be prevented by taking non-radioactive, 'cold' iodine as tablets. Iodine tablets dilute the radioactive iodine that has entered the body. A dose of iodine also paralyses the thyroid temporarily by saturating its iodine-carrying capacity. To be useful iodine tablets should be taken immediately when a radioactive emission has occurred. If the tablets are taken too early or too late, they give little protection. Iodine tablets should not be taken just to be on the safe side, since their use may involve harmful side effects. Dosing instructions should also be followed with care. (orig.)

  4. Demonstration of pharmaceutical tablet coating process by injection molding technology.

    Science.gov (United States)

    Puri, Vibha; Brancazio, David; Harinath, Eranda; Martinez, Alexander R; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Braatz, Richard D; Myerson, Allan S; Trout, Bernhardt L

    2018-01-15

    We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Formulation and evaluation of glipizide floating-bioadhesive tablets

    Directory of Open Access Journals (Sweden)

    Jayvadan K. Patel

    2010-10-01

    Full Text Available The purpose of this study was formulation and in vitro evaluation of floating-bioadhesive tablets to lengthen the stay of glipizide in its absorption area. Effervescent tablets were made using chitosan (CH, hydroxypropyl methylcellulose (HPMC, carbopolP934 (CP, polymethacrylic acid (PMA, citric acid, and sodium bicarbonate. Tablets with 5% effervescent base had longer lag time than 10%. The type of polymer had no significant effect on the floating lag time. All tablets floated atop the medium for 23-24 hr. Increasing carbopolP934 caused higher bioadhesion than chitosan (p < 0.05. All formulations showed a Higuchi, non-Fickian release mechanism. Tablets with 10% effervescent base, 80% CH/20% HPMC, or 80% CP/20% PMA seemed desirable.

  6. Amorphization within the tablet

    DEFF Research Database (Denmark)

    Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A.

    2017-01-01

    , the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization......, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90 kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements...

  7. Android tablets for dummies

    CERN Document Server

    Gookin, Dan

    2015-01-01

    Learn all you need to know about your Android tablet in one quick and easy reference! It's not a computer and it's not a smartphone-so what in the world is it? Whether you're new to Android or new to tablets altogether, you're about to experience mobile computing like never before with this fun, full-color guide! Inside, longtime and bestselling author Dan Gookin walks you through setting up your Android tablet, navigating the interface, browsing the web, setting up email, connecting to social media, finding plenty of apps, music, books, and movies to indulge your interests-and so much more.

  8. Based Indomethacin Sustained-Release Tablets

    African Journals Online (AJOL)

    Owing to the short biological half-life of this drug, a sustained ... tendency. This work is aimed at formulating sustained ... Chemie GmbH, Germany), Phospholipon® 90H. (Phospholipid ... weighed out in an analytical balance and dispersed in ...

  9. Grasp interaction with tablets

    CERN Document Server

    Wolf, Katrin

    2015-01-01

    This book presents guidelines for a future device type: a tablet that allows ergonomic front- and back-of-device interaction. These guidelines help designers and developers of user interfaces to build ergonomic applications for tablet devices, in particular for devices that enable back-of-device interaction. In addition, manufacturers of tablet devices obtain arguments that back-of-device interaction is a promising extension of the interaction design space and results in increased input capabilities, enriched design possibilities, and proven usability. The guidelines are derived from empirical studies and developed to fit the users’ skills to the way the novel device type is held. Three particular research areas that are relevant to develop design guidelines for tablet interaction are investigated: ergonomic gestures, interaction areas, and pointing techniques.

  10. Two-step irradiance schedule versus single-dose tramadol sustained-release tablets for pain control during topical 5-aminolevulinic acid-photodynamic therapy of condyloma acuminatum in Chinese patients: a randomized comparative study.

    Science.gov (United States)

    Mchepange, Uwesu O; Huang, Chun-Yan; Sun, Yi; Tu, Ya-Ting; Tao, Juan

    2014-07-01

    Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients. Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation. The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial. The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes). The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056). Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain. © 2014 Wiley Periodicals

  11. Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP.

    Science.gov (United States)

    Krashes, Michael J; Shah, Bhavik P; Koda, Shuichi; Lowell, Bradford B

    2013-10-01

    Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (neuropeptide Y [NPY] and Agouti-related peptide [AgRP]). This raises questions as to their respective functions. The acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY, or GABA agonist results in the marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. After the acute stimulation of AgRP neurons with DREADD technology, we found that either GABA or NPY is required for the rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

    Science.gov (United States)

    Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

    2017-11-01

    Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  13. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  14. Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Etminan, Nima; Macdonald, R Loch; Davis, Cara; Burton, Kevin; Steiger, Hans-Jakob; Hänggi, Daniel

    2015-01-01

    The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.

  15. A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

    Science.gov (United States)

    Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

    2018-02-01

    Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

  16. Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

    Science.gov (United States)

    Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

    2018-01-01

    Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully

  17. Quality by design I: Application of failure mode effect analysis (FMEA) and Plackett-Burman design of experiments in the identification of "main factors" in the formulation and process design space for roller-compacted ciprofloxacin hydrochloride immediate-release tablets.

    Science.gov (United States)

    Fahmy, Raafat; Kona, Ravikanth; Dandu, Ramesh; Xie, Walter; Claycamp, Gregg; Hoag, Stephen W

    2012-12-01

    As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system. Granules were manufactured using an Alexanderwerk WP120 roller compactor and tablets were compressed on a Stokes B2 tablet press. In the early stages of development, prior knowledge was systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA). The factors identified using FMEA were then followed by a quantitative assessed using a Plackett-Burman screening design. Results show that by using prior experience, literature data, and preformulation data the number of experiments could be reduced to an acceptable level, and the use of FMEA and screening designs such as the Plackett Burman can rationally guide the process of reducing the number experiments to a manageable level.

  18. Formulation and Evaluation of Tramadol HCl Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation and Evaluation of Tramadol HCl Matrix Tablets Using Carbopol ... to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous ...

  19. Development and evaluation of microporous osmotic tablets of diltiazem hydrochloride

    Directory of Open Access Journals (Sweden)

    Afifa Bathool

    2012-01-01

    Full Text Available Microporous osmotic tablet of diltiazem hydrochloride was developed for colon targeting. These prepared microporous osmotic pump tablet did not require laser drilling to deliver the drug to the specific site of action. The tablets were prepared by wet granulation method. The prepared tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan coating process. The incorporation of sodium lauryl sulfate (SLS, a leachable pore-forming agent, could form in situ delivery pores while coming in contact with gastrointestinal medium. The effect of formulation variables was studied by changing the amounts of sodium alginate and NaCMC in the tablet core, osmogen, and that of pore-forming agent (SLS used in the semipermeable coating. As the amount of hydrophilic polymers increased, drug release rate prolonged. It was found that drug release was increased as the concentration of osmogen and pore-former was increased. Fourier transform infrared spectroscopy and Differential scanning calorimetry results showed that there was no interaction between drug and polymers. Scanning electron microscopic studies showed the formation of pores after predetermined time of coming in contact with dissolution medium. The formation of pores was dependent on the amount of pore former used in the semipermeable membrane. in vitro results showed acid-resistant, timed release at an almost zero order up to 24 hours. The developed osmotic tablets could be effectively used for prolonged delivery of Diltiazem HCl.

  20. Evaluation of an enteric coated naproxen tablet using gamma scintigraphy and pH monitoring

    International Nuclear Information System (INIS)

    Hardy, J.G.; Evans, D.F.; Zaki, I.; Clark, A.G.; Toennesen, H.H.

    1987-01-01

    Enteric coated naproxen tablets and pH-sensitive radiotelemetry capsules were both radiolabelled and administered to 6 healthy volunteers following breakfast. The median gastric emptying times for the tablets and capsules were 3.3 h and 4.2 h, respectively. In general, the intragastric pH remained below 2 with only transient increases following food comsumption. Five of the naproxen tablets disintegrated in the small intestine and one in the stomach. In the ileum the pH was greater than 6 resulting in a mean time for tablet disintegration of 1.2 h after gastric emptying. There was a close correlation between tablet disintegration and the first detection of naproxen in the blood. Peak plasma concentrations of the drug occurred 4 h after tablet disintegration. This study has demonstrated that gastric emptying is the main factor influencing the onset of drug release from enteric coated tablets. 8 refs.; 3 figs.; 3 tabs

  1. Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine

    DEFF Research Database (Denmark)

    Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev

    2015-01-01

    –arginine in a larger production scale. In this work, a tablet formulation was developed for a co-amorphous salt, namely spray dried indomethacin–arginine (SD IND–ARG). The effects of compaction pressure on tablet properties, physical stability and dissolution profiles under non-sink conditions were examined....... Dissolution profiles of tablets with SD IND–ARG (TAB SD IND–ARG) were compared to those of tablets containing a physical mixture of crystalline IND and ARG (TAB PM IND–ARG) and to the dissolution of pure spray dried powder. Concerning tableting, the developed formulation allowed for the preparation of tablets...... with a broad range of compaction pressures resulting in different porosities and tensile strengths. XRPD results showed that, overall, no crystallization occurred neither during tableting nor during long-term storage. Dissolution profiles of TAB SD IND–ARG showed an immediate release of IND by erosion...

  2. A new tablet brittleness index.

    Science.gov (United States)

    Gong, Xingchu; Sun, Changquan Calvin

    2015-06-01

    Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Dissolution test for glibenclamide tablets

    Directory of Open Access Journals (Sweden)

    Elisabeth Aparecida dos Santos Gianotto

    2007-10-01

    Full Text Available The aim of this work is to develop and validate a dissolution test for glibenclamide tablets. Optimal conditions to carry out the dissolution test are 500 mL of phosphate buffer at pH 8.0, paddles at 75 rpm stirring speed, time test set to 60 min and using equipment with six vessels. The derivative UV spectrophotometric method for determination of glibenclamide released was developed, validated and compared with the HPLC method. The UVDS method presents linearity (r² = 0.9999 in the concentration range of 5-14 µg/mL. Precision and recoveries were 0.42% and 100.25%, respectively. The method was applied to three products commercially available on the Brazilian market.

  4. Viability of lactobacillus acidophilus in various vaginal tablet formulations

    Directory of Open Access Journals (Sweden)

    Fazeli M.R.

    2006-07-01

    Full Text Available The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-release vaginal tablets prepared by using six different retarding polymers and from two effervescent tablets prepared by using citric or adipic acid. The Carbomer–based formulations showed high initial viablility compared to those based on HPMC-LV, HPMC-HV, Polycarbophil and SCMC polymers which showed one log decrease in viable cells. All retarding polymers in slow release formulations presented a strong bacterial release at about 2 h except Carbomer polymers which showed to be poor bacterial releasers. Although effervescent formulations produced a quick bacterial release in comparison with polymer based slow-release tablets, they were less stable in cold storage. Due to the strong chelating characteristic of citric acid, the viability was quickly lost for aqueous medium of citric acid in comparison with adipic acid based effervescent tablets.

  5. The Impact of Amorphisation and Spheronization Techniques on the Improved in Vitro & in Vivo Performance of Glimepiride Tablets

    Directory of Open Access Journals (Sweden)

    Rana Refaat Makar

    2017-12-01

    Full Text Available Purpose: Triple solid dispersion adsorbates (TSDads and spherical agglomerates (SA present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively. Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo.

  6. Feasibility of mini-tablets as a flexible drug delivery tool.

    Science.gov (United States)

    Mitra, Biplob; Chang, Jessica; Wu, Sy-Juen; Wolfe, Chad N; Ternik, Robert L; Gunter, Thomas Z; Victor, Michael C

    2017-06-15

    Mini-tablets have potential applications as a flexible drug delivery tool in addition to their generally perceived use as multi-particulates. That is, mini-tablets could provide flexibility in dose finding studies and/or allow for combination therapies in the clinic. Moreover, mini-tablets with well controlled quality attributes could be a prudent choice for administering solid dosage forms as a single unit or composite of multiple mini-tablets in patient populations with swallowing difficulties (e.g., pediatric and geriatric populations). This work demonstrated drug substance particle size and concentration ranges that achieve acceptable mini-tablet quality attributes for use as a single or composite dosage unit. Immediate release and orally disintegrating mini-tablet formulations with 30μm to 350μm (particle size d 90 ) acetaminophen and Compap™ L (90% acetaminophen) at concentrations equivalent to 6.7% and 26.7% acetaminophen were evaluated. Mini-tablets achieved acceptable weight variability, tensile strength, friability, and disintegration time at a reasonable solid fraction for each formulation. The content uniformity was acceptable for mini-tablets of 6.7% formulations with ≤170μm drug substance, mini-tablets of all 26.7% formulations, and composite dosage units containing five or more mini-tablets of any formulation. Results supported the manufacturing feasibility of quality mini-tablets, and their applicability as a flexible drug delivery tool. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Tablets and tablet production - with special reference to Icelandic conditions].

    Science.gov (United States)

    Skaftason, Jóhannes F; Jóhannesson, Thorkell

    2013-04-01

    Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades.

  8. Teach yourself visually Fire tablets

    CERN Document Server

    Marmel, Elaine

    2014-01-01

    Expert visual guidance to getting the most out of your Fire tablet Teach Yourself VISUALLY Fire Tablets is the comprehensive guide to getting the most out of your new Fire tablet. Learn to find and read new bestsellers through the Kindle app, browse the app store to find top games, surf the web, send e-mail, shop online, and much more! With expert guidance laid out in a highly visual style, this book is perfect for those new to the Fire tablet, providing all the information you need to get the most out of your device. Abundant screenshots of the Fire tablet graphically rich, touch-based Androi

  9. The Nebusarsekim Tablet

    NARCIS (Netherlands)

    Stadhouders, H.A.I.

    2008-01-01

    During the summer of 2007 an internet hype was unleashed by the breaking news that an Old Testament name of some importance, figuring in the Book of Jeremiah Ch. 39, had been positively identified on a cuneiform clay tablet, viz. a bill of receipt from the time of this prophet's floruit. Many a

  10. Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

    Science.gov (United States)

    Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

    2015-09-01

    Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

  11. Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Sateesh Kumar Vemula

    2013-01-01

    Full Text Available The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4 showed almost complete drug release in the colon (99.86% within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period. The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The Cmax of colon targeted tablets was 11956.15 ng/mL at Tmax of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.

  12. Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics

    Science.gov (United States)

    Bontha, Vijaya Kumar

    2013-01-01

    The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C max of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen. PMID:24260738

  13. Developing a mapping tool for tablets

    Science.gov (United States)

    Vaughan, Alan; Collins, Nathan; Krus, Mike

    2014-05-01

    Digital field mapping offers significant benefits when compared with traditional paper mapping techniques in that it provides closer integration with downstream geological modelling and analysis. It also provides the mapper with the ability to rapidly integrate new data with existing databases without the potential degradation caused by repeated manual transcription of numeric, graphical and meta-data. In order to achieve these benefits, a number of PC-based digital mapping tools are available which have been developed for specific communities, eg the BGS•SIGMA project, Midland Valley's FieldMove®, and a range of solutions based on ArcGIS® software, which can be combined with either traditional or digital orientation and data collection tools. However, with the now widespread availability of inexpensive tablets and smart phones, a user led demand for a fully integrated tablet mapping tool has arisen. This poster describes the development of a tablet-based mapping environment specifically designed for geologists. The challenge was to deliver a system that would feel sufficiently close to the flexibility of paper-based geological mapping while being implemented on a consumer communication and entertainment device. The first release of a tablet-based geological mapping system from this project is illustrated and will be shown as implemented on an iPad during the poster session. Midland Valley is pioneering tablet-based mapping and, along with its industrial and academic partners, will be using the application in field based projects throughout this year and will be integrating feedback in further developments of this technology.

  14. Magnetic resonance imaging of tablet dissolution.

    Science.gov (United States)

    Nott, Kevin P

    2010-01-01

    Magnetic resonance imaging (MRI) is the technique of choice for measuring hydration, and its effects, during dissolution of tablets since it non-invasively maps (1)H nuclei associated with 'mobile' water. Although most studies have used MRI systems with high-field superconducting magnets, low-field laboratory-based instruments based on permanent magnet technology are being developed that provide key data for the formulation scientist. Incorporation of dissolution hardware, in particular the United States Pharmacopeia (USP) apparatus 4 flow-through cell, allows measurements under controlled conditions for comparison against other dissolution methods. Furthermore, simultaneous image acquisition and measurement of drug concentration allow direct comparison of the drug release throughout the hydration process. The combination of low-field MRI with USP-4 apparatus provides another tool to aid tablet formulation. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

    Science.gov (United States)

    Ducharme, M P; Edwards, D J; McNamara, P J; Stoeckel, K

    1993-12-01

    Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food.

  16. Buccals tablets - literature search

    OpenAIRE

    Horáček, Jan

    2007-01-01

    BUCCAL TABLETS Jan Horáček ABSTRACT My diploma thesis was aimed at summarising information about phenomena of bioadhesion in connection with administration of drugs. The work describes anatomy and physiology of oral mucosa and differencies in various parts of oral cavity. It refers about advantages and limits of administrating drugs through the oral mucosa. The part called Bioadhesion / mucoadhesion includes definition, theories, influencing factors and description of methods to determinate b...

  17. Modified geometry three-layered tablet as a platform for class II ...

    African Journals Online (AJOL)

    Modified geometry three-layered tablet as a platform for class II drugs zero-order release system. Abdullah Monahi Albogami, Mustafa E. Omer, Abdulkareem M. Al Bekairy, Abdulmalik Alkatheri, Alaa Eldeen B. Yassin ...

  18. Plasticisation of amylodextrin by moisture. Consequences for compaction behaviour and tablet properties

    NARCIS (Netherlands)

    Steendam, R; Frijlink, H W; Lerk, C F

    2001-01-01

    Purpose: Amylodextrin, a starch-based controlled release excipient, spontaneously absorbs moisture during storage. The aim of this study was to investigate plasticisation of amylodextrin by moisture and its effect on compaction and tablet characteristics. Methods: The glass transition temperature

  19. Fused-filament 3D printing (3DP) for fabrication of tablets.

    Science.gov (United States)

    Goyanes, Alvaro; Buanz, Asma B M; Basit, Abdul W; Gaisford, Simon

    2014-12-10

    The use of fused-filament 3D printing (FF 3DP) to fabricate individual tablets is demonstrated. The technology permits the manufacture of tablets containing drug doses tailored to individual patients, or to fabrication of tablets with specific drug-release profiles. Commercially produced polyvinyl alcohol (PVA) filament was loaded with a model drug (fluorescein) by swelling of the polymer in ethanolic drug solution. A final drug-loading of 0.29% w/w was achieved. Tablets of PVA/fluorescein (10 mm diameter) were printed using a 3D printer. It was found that changing the degree of infill percentage in the printer software varied the weight and volume of the printed tablets. The tablets were mechanically strong and no significant thermal degradation of the active occurred during printing. Dissolution tests were conducted in modified Hank's buffer. The results showed release profiles were dependent on the infill percentage used to print the tablet. The study indicates that FF 3DP has the potential to offer a new solution for fabricating personalized-dose medicines or unit dosage forms with controlled-release profiles. In addition, the low cost of FDM printers means the paradigm of extemporaneous or point-of-use manufacture of personalized-dose tablets is both feasible and attainable. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

    Directory of Open Access Journals (Sweden)

    Labib GS

    2015-09-01

    Full Text Available Gihan S Labib1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Objectives: Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will.Materials and methods: Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability.Results: All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets.Conclusion: Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these

  1. DESIGN AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS WITH NATURAL AND SYNTHETIC POLYMERS

    OpenAIRE

    R. L. C. Sasidhar et al.

    2012-01-01

    The objective of the study was to formulate controlled release matrix tablets of losartan Potassium by using a combination of hydrophilic synthetic polymer like poly (ethylene oxides) and natural gums like xanthan gum, karaya gum and guar gum. A combination of synthetic hydrophobic polymers like methacrylates with synthetic hydrophilic polymer like poly (ethylene oxide) was also used in the preparation of matrix tablets and evaluated for their influence on controlled drug release. The matrix ...

  2. Do the characteristics of xanthan single molecule reflect the behavior of matrix tablets?

    OpenAIRE

    Sepe, Ana; Mikac, Urška; Zupančič-Valant, Andreja; Srčič, Stanko; Govedarica, Biljana; Baumgartner, Saša; Kristl, Julijana

    2015-01-01

    Introduction: Xanthan (XAN) is a well known negatively charged biopolymer thatadopts different conformations in media, which are still poorly understood. XAN tablets in contact with water hydrate, forming a gel layer that regulates the drug release rate [1]. The hypothesis was that XAN molecular structure influences the drug release from matrix tablets. Thus, detailed studies on molecular as well as on macro-scale level were performed. Experimental: To determine XAN molecular conformations, i...

  3. Double-layer Tablets of Lornoxicam: Validation of Quantification ...

    African Journals Online (AJOL)

    Purpose: To formulate double-layer tablets of lornoxicam (LRX) prepared by direct compression method and ... including direct compression method which is ..... Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J Pharm Sci 1983; 72(10): 1189-1191. 17.

  4. Formulation and Evaluation of Tramadol HCl Matrix Tablets Using ...

    African Journals Online (AJOL)

    Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. ... analysis indicates that drug release mechanism was anomalous non-Fickian diffusion. Conclusion: Both .... and other the reference standard, Food and Drug .... Compliance Regulatory Information/Gui dances/.

  5. Formulation and Evaluation of Mouth Dissolving Tablets of Tramadol ...

    African Journals Online (AJOL)

    Results: The tablet formulation prepared with Pharmaburst (F13) showed good flow properties, low disintegration time (15 s) and improved drug release (99 % at 30 min) compared with those of the reference product (88 % at 30 min) and passed 6 months accelerated stability test. Bioequivalence of the test product with that ...

  6. 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.

  7. Modulatory effect of polymer type and composition on drug release ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of polymer type and composition on drug release from the matrix of diclofenac sodium sustained release tablets formulated using three different granulation methods. Ten (10) batches of diclofenac sodium tablets (F01 - F10) were prepared by melt granulation, ...

  8. Sustained Release of a Watermgoluble tiring from Directly ...

    African Journals Online (AJOL)

    Sustained Release of a Watermgoluble tiring from Directly Compressed Okra Gum Matrix. Tablets. Val). Mill, MA. Gilllllbll'ifl'l' AND KT. ... in near noromorder release of aspirin from the matrix tablets. The results indicate that okra gum is .... porous structure including alteration of the shape and size distribution of the pores.

  9. Teste de dissolução para avaliação de liberação de glibenclamida em comprimidos Glibenclamide dissolution test for drug release evaluation in tablets

    Directory of Open Access Journals (Sweden)

    Christiane Gino Colu Nery

    2007-09-01

    Full Text Available A glibenclamida (GLIB ou gliburida, é um hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, usado sob a forma de comprimidos para tratamento do diabetes mellitus. Variações no tratamento podem ocorrer, devido à baixa solubilidade do fármaco em comprimidos. A comparação de várias formulações de comprimidos piloto com comprimidos do medicamento referência (Daonil®, glibenclamida 5 mg comprimidos, Aventis Pharma Ltda. foi avaliada por meio do desenvolvimento de um teste de dissolução sem adição de solventes orgânicos ou tensoativos no meio, que mostrou ser discriminativo para as diferentes formulações farmacêuticas propostas. A quantificação de GLIB foi realizada por meio de cromatografia líquida de alta eficiência em fase reversa (CLAE-FR, método previamente validado. A partir de vários ensaios de perfil de dissolução testados comparativamente àquele de comprimidos do medicamento referência, verificou-se o potencial de determinada formulação proposta (f1 4,04 and f2 69,35 como candidata a medicamento genérico no mercado brasileiro.Glibenclamide (GLIB or glyburide, a second-generation hypoglycemic agent is used per oral as tablets for the treatment of diabetes mellitus. Much variabilility in the treatment may occur because of the low drug aqueous solubility in tablets dosage forms. This work reports the comparison of several pilot formulation batches with the commercial reference drug dosage form (Daonil®, glibenclamide 5 mg per tablet, Aventis Pharma Ltda.. A feasible dissolution test, developed with no use of organic solvents or surfactants in the medium, showed to be discriminative regarding to different formulations tested. GLIB quantitation was performed by a previously validated reverse-phase high performance liquid chromatography (RP-HPLC. Among several dissolution profiles compared with that of a commercial reference, a potential for a generic candidate was evident (f1 4.04 and f2 69

  10. Formulation and evaluation of aceclofenac mouth-dissolving tablet

    Directory of Open Access Journals (Sweden)

    Shailendra Singh Solanki

    2011-01-01

    Full Text Available Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities similar to indomethacin and diclofenac, and due to its preferential Cox-2 blockade, it has a better safety than conventional Non steroidal anti-inflammatory drug (NSAIDs with respect to adverse effect on gastrointestinal and cardiovascular systems. Aceclofenac is superior from other NSAIDs as it has selectivity for Cox-2, a beneficial Cox inhibitor is well tolerated, has better Gastrointestinal (GI tolerability and improved cardiovascular safety when compared with other selective Cox-2 inhibitor. To provide the patient with the most convenient mode of administration, there is need to develop a fast-disintegrating dosage form, particularly one that disintegrates and dissolves/disperses in saliva and can be administered without water, anywhere, any time. Such tablets are also called as "melt in mouth tablet." Direct compression, freeze drying, sublimation, spray drying, tablet molding, disintegrant addition, and use of sugar-based excipients are technologies available for mouth-dissolving tablet. Mouth-dissolving tablets of aceclofenac were prepared with two different techniques, wet granulation and direct compression, in which different formulations were prepared with varying concentration of excipients. These tablets were evaluated for their friability, hardness, wetting time, and disintegration time; the drug release profile was studied in buffer Phosphate buffered Saline (PBS pH 7.4. Direct compression batch C3 gave far better dissolution than the wet granulation Batch F2, which released only 75.37% drug, and C3, which released 89.69% drug in 90 minutes.

  11. Tablets i skolen

    DEFF Research Database (Denmark)

    Lorentzen, Rasmus Fink

    2012-01-01

    Denne rapport afslutter CELMS undersøgelse af Odder Kommunes projekt med indførelse af iPads på alle kommunens skoler. Undersøgelsen har til formål at belyse om der er pædagogiske og læringsmæssige fordele forbundet med brugen af tablets i undervisningen i grundskolen og i givet fald hvilke...... designer og tablet’ens egenskaber i et generelt perspektiv. Rapporten afsluttes med en række anbefalinger til henholdsvis lærere og skoleledere med henblik på videre udvikling af indsatsen....

  12. A new experimental design method to optimize formulations focusing on a lubricant for hydrophilic matrix tablets.

    Science.gov (United States)

    Choi, Du Hyung; Shin, Sangmun; Khoa Viet Truong, Nguyen; Jeong, Seong Hoon

    2012-09-01

    A robust experimental design method was developed with the well-established response surface methodology and time series modeling to facilitate the formulation development process with magnesium stearate incorporated into hydrophilic matrix tablets. Two directional analyses and a time-oriented model were utilized to optimize the experimental responses. Evaluations of tablet gelation and drug release were conducted with two factors x₁ and x₂: one was a formulation factor (the amount of magnesium stearate) and the other was a processing factor (mixing time), respectively. Moreover, different batch sizes (100 and 500 tablet batches) were also evaluated to investigate an effect of batch size. The selected input control factors were arranged in a mixture simplex lattice design with 13 experimental runs. The obtained optimal settings of magnesium stearate for gelation were 0.46 g, 2.76 min (mixing time) for a 100 tablet batch and 1.54 g, 6.51 min for a 500 tablet batch. The optimal settings for drug release were 0.33 g, 7.99 min for a 100 tablet batch and 1.54 g, 6.51 min for a 500 tablet batch. The exact ratio and mixing time of magnesium stearate could be formulated according to the resulting hydrophilic matrix tablet properties. The newly designed experimental method provided very useful information for characterizing significant factors and hence to obtain optimum formulations allowing for a systematic and reliable experimental design method.

  13. Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

    Science.gov (United States)

    Labib, Gihan S

    2015-01-01

    Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

  14. Application and Characterization of Gum from Bombax buonopozense Calyxesas an Excipient in Tablet Formulation

    Science.gov (United States)

    Ngwuluka, Ndidi C.; Kyari, Jehu; Taplong, John; Uwaezuoke, Onyinye J.

    2012-01-01

    This study was undertaken to explore gum from Bombax buonopozense calyxes as a binding agent in formulation of immediate release dosage forms using wet granulation method. The granules were characterized to assess the flow and compression properties and when compressed, non-compendial and compendial tests were undertaken to assess the tablet properties for tablets prepared with bombax gum in comparison with those prepared with tragacanth and acacia gums. Granules prepared with bombax exhibited good flow and compressible properties with angle of repose 28.60°, Carr’s compressibility of 21.30% and Hausner’s quotient of 1.27. The tablets were hard, but did not disintegrate after one hour. Furthermore, only 52.5% of paracetamol was released after one hour. The drug release profile followed zero order kinetics. Tablets prepared with bombax gum have the potential to deliver drugs in a controlled manner over a prolonged period at a constant rate. PMID:24300296

  15. Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

    Science.gov (United States)

    Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su

    2017-04-28

    As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

  16. Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Raghvendra Misra

    2016-01-01

    Full Text Available The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3 and citric acid were used as gas (CO2 generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72±2.49 seconds and duration of floating 24.50±0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr.

  17. Construcción sustentable, análisis de retraso térmico a bloques de tierra comprimidos / Sustainable building, thermal analysis of delay to earth blocks tablets

    Directory of Open Access Journals (Sweden)

    Roux Gutiérrez, Rubén Salvador

    2015-09-01

    Full Text Available Este artículo es el resultado de la investigación que aborda el tema las propiedades térmicas de los Bloques de Tierra Comprimida (BTC, para corroborar las ventajas de este material de construcción alternativo, sobre los materiales convencionales, para comprobar que estos materiales pueden satisfacer las necesidades de la población en la construcción de sus viviendas digna, mejorando la calidad de vida del usuario y produciendo un menor impacto ambiental. Se plantea el uso de BTC como unidad de análisis, elaborado con material de la zona del sur de Tamaulipas, probando sus ventajas como regulador natural de temperatura contra el bloque de concreto y el ladrillo recocido de la región, que son empleados en el ámbito de la construcción de viviendas. Las pruebas térmicas realizadas fueron simulando el efecto del sol sobre un muro, registrándose la temperatura durante las pruebas determinándose el retraso térmico en los muros dependiendo del material. Es así como con el resultado de las pruebas se determinó cual es el material óptimo para emplear como envolvente de la vivienda. This article is the result of research that addresses the issue the thermal properties of the Compressed Earth Blocks (CEB, to corroborate the benefits of this alternative building material, on the conventional materials, to verify that these materials can meet the needs of the population in the construction of their homes worthy, improving the quality of life of the user and producing a lower environmental impact. Considering the use of CEB as a unit of analysis, developed with materials from the area of southern Tamaulipas, proving its advantages as natural regulator of temperature against the concrete block and brick annealing of the region, who are employed in the field of housing construction. Thermal testing carried out were simulating the effect of the sun on a wall, the temperature recorded during the tests determined the delay in the thermal walls

  18. Dissolution Behavior and Content Uniformity of An Improved Tablet Formulation Assayed by Spectrofluorometric and RIA Methods

    Directory of Open Access Journals (Sweden)

    Morteza Rafiee-Tehrani

    1990-06-01

    Full Text Available Digoxin 0.25 mg tablets were manufactured by pregranulation of lactose-fcorn starch with 10% corn starch paste and deposition of solvent on pregranules to make digoxin granules. In the preparation of tablet A, granules of lactose-corn Starch was uniformly moistened with a 5% chloroform-ethanol solution (2:lv/vof digoxin by a simple blending. Tablet B was produced by spray granulation system on which the solvent was sprayed on the granules of lactose-corn starch by utilization of a laboratory size fluidized bed drier (Uniglatt . The content uniformity and dissolution of both tablets were determined by the spectrofluorometric and radio¬immunoassay (RIA method modified for the assay of tablet solutious. One available commercially brand of digoxin tablet (C was included in dissolution study for comparison. For the spectrofluorometric method the technique is based on the fluor-ometric measurenent of the dehydration product of the cardiotonic steroid resulting from its reaction with hydrogen peroxide in concentrated hydrochloric acid. For the RIA method, the filtrate was diluted to theoretical concentration of 2.5 ng/ml."nAliquots of this dilution were then assayed for digoxin content using a commercial digoxin125 I RIA kit. Results from both assay methods were extrapolated to the total tablet content and compared with the labeled amount of 20 individual tablets. All tablet assay results were within the USP standards for the content uniformity and"ndissolution of individual. The individual tablet deviations from labeled amount by RIA method were smaller when compared with the spectrofluorometric method.There was no significant difference between the release of digoxin from three products, and thus it is suggested that the Procedure B could be easily applied for manufacturing"nof digoxin tablets in industrial scales.It was also concluded that,the RIA method could be used for the digoxin tablet determination.

  19. The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs.

    Science.gov (United States)

    KuKanich, K; KuKanich, B

    2015-04-01

    The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (CMAX ) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·μg/mL, CMAX 0.43 μg/mL) than with doxycycline alone (AUC 36.0 h·μg/mL, CMAX 2.53 μg/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs. © 2014 John Wiley & Sons Ltd.

  20. Delayed power analysis

    International Nuclear Information System (INIS)

    Adamovich, L.A.; Azarov, V.V.

    1999-01-01

    Time dependent core power behavior in a nuclear reactor is described with well-known neutron kinetics equations. At the same time, two portions are distinguished in energy released from uranium nuclei fission; one released directly at fission and another delayed (residual) portion produced during radioactive decay of fission products. While prompt power is definitely described with kinetics equations, the delayed power presentation still remains outstanding. Since in operation the delayed power part is relatively small (about 6%) operation, it can be neglected for small reactivity disturbances assuming that entire power obeys neutron kinetics equations. In case of a high negative reactivity rapidly inserted in core (e.g. reactor scram initiation) the prompt and delayed components can be calculated separately with practically no impact on each other, employing kinetics equations for prompt power and known approximation formulas for delayed portion, named residual in this specific case. Under substantial disturbances the prompt component in the dynamic process becomes commensurable with delayed portion, thus making necessary to take into account their cross impact. A system of differential equations to describe time-dependent behavior of delayed power is presented. Specific NPP analysis shows a way to significantly simplify the task formulation. (author)

  1. Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties.

    Science.gov (United States)

    Mohamed, Saifulla P; Muzzammil, Shariff; Pramod, Kumar T M

    2011-04-01

    The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.

  2. A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system.

    Science.gov (United States)

    Senyigit, Zeynep Ay; Vetter, Anja; Guneri, Tamer; Bernkop-Schnürch, Andreas

    2011-08-01

    The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties. Thereafter, the gastric residence times of tablets were determined with in vivo study in rats. The resulting PAA-Cys and chitosan-TBA conjugates displayed 172.80 ± 30.33 and 371.11 ± 72.74 µmol free thiol groups, respectively. Disintegration studies demonstrated the stability of thiolated tablets up to 24 h, whereas tablets prepared with unmodified PAA and chitosan disintegrated within a time period of 1 h. Mucoadhesion studies showed that mucoadhesion work of PAA-Cys and chitosan-TBA tablets were 1.341- and 2.139-times higher than unmodified ones. The mucoadhesion times of PAA, PAA-Cys, chitosan, and chitosan-TBA tablets were 1.5 ± 0.5, 21 ± 1, 1 ± 0.5, 17 ± 1 h, respectively. These results confirm the theory that thiol groups react with mucin glycoproteins and form covalent bonds to the mucus layer. Release studies indicated that a controlled release was provided with thiolated tablets up to 24 h. These promising in vitro results of thiolated tablets were proved with in vivo studies. The thiolated tablets showed a gastroretention time up to 6 h, whereas unmodified tablets completely disintegrated within 1 h in rat stomach. Consequently, the study suggests that thiolated matrix tablets might be promising formulations for gastroretentive delivery systems.

  3. Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

    Science.gov (United States)

    Vats, Anima; Pathak, Kamla

    2012-11-01

    In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

  4. The effect of superdisintegrants on the properties and dissolution profiles of liquisolid tablets containing rosuvastatin.

    Science.gov (United States)

    Vraníková, Barbora; Gajdziok, Jan; Doležel, Petr

    2017-03-01

    The preparation of liquisolid systems (LSS) represents a promising method for enhancing a dissolution rate and bioavailability of poorly soluble drugs. The release of the drug from LSS tablets is affected by many factors, including the disintegration time. The evaluation of differences among LSS containing varying amounts and types of commercially used superdisintegrants (Kollidon® CL-F, Vivasol® and Explotab®). LSS were prepared by spraying rosuvastatin solution onto Neusilin® US2 and further processing into tablets. Varying amounts of superdisintegrants were used and the differences among LSS were evaluated. The multiple scatter plot method was used to visualize the relationships within the obtained data. All disintegrants do not showed negative effect on the flow properties of powder blends. The type and concentration of superdisintegrant had an impact on the disintegration time and dissolution profiles of tablets. Tablets with Explotab® showed the longest disintegration time and the smallest amount of released drug. Fastest disintegration and dissolution rate were observed in tablets containing Kollidon® CL-F (≥2.5% w/w). Also tablets with Vivasol® (2.5-4.0% w/w) showed fast disintegration and complete drug release. Kollidon® CL-F and Vivasol® in concentration ≥2.5% are suitable superdisintegrants for LSS with enhanced release of drug.

  5. Development and Characterization of Mouth Dissolving Tablet of Zolmitriptan

    Directory of Open Access Journals (Sweden)

    Sudarshan Singh

    2012-05-01

    Full Text Available Objective: To formulate and Characterize Mouth Dissolving Tablet of Zolmitriptan to produce the intended benefits. Methods: Tablets were prepared using a direct compression method employing superdisintegrants such as Kyron T-314, Crospovidone, Croscarmellose Sodium, and Sodium Starch Glycolate. Tablets of Zolmitriptan prepared using Kyron T-314 exhibited the least friability and disintegration time 35 seconds. To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of Mouth Dissolving Tablet (MDTs. The addition of camphor as a subliming agent lowered the disintegration time 10 seconds further, but the percent friability was increased. A 32 full factorial design was employed to study the joint influence of the amount of superdisintegrant (Kyron T-314 and the amount of sublimating agent (Camphor on the percent of friability and the disintegration time. Results: The results of multiple linear regression analysis revealed that an effective MDT of Zolmitriptan requires higher percentages of Kyron T-314 and camphor should be used. The approach using the optimization technique helped to produce a detailed understanding effect of formulation parameters. An optimized formulation was found to have good hardness, wetting time, disintegration time. Release kinetic model study indicated that all the formulations follow zero order kinetics. It also indicated that batch F1, F2, F5 and F8 releases the drug at constant rate as well as fast rate as per the Weibull model which was also confirmed by HixsonCrowell model. Stability studies indicated that there are no significant changes in hardness, Percentage friability, drug content and in-vitro disintegration time and cumulative percentage drug release. Conclusions: Thus, it was concluded that by adopting a systematic formulation approach, Zolmitriptan Mouth dissolving tablet could be formulated using superdisintegrants in combination with

  6. Formulation and evaluation of sublingual tablets of losartan potassium

    Directory of Open Access Journals (Sweden)

    Nikunj J. Aghera

    2012-05-01

    Full Text Available Objective: Sublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination. Methods: The Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined. Results: FTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3 was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %. Conclusions: Sublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.

  7. Development and evaluation of novel antihypertensive orodispersible tablets.

    Science.gov (United States)

    Khan, Hafeez Ullah; Hanif, Muhammad; Sarfraz, Rai M; Maheen, Safirah; Afzal, Samina; Sher, Muhammad; Afzal, Khurram; Mahmood, Asif; Shamim, Ayesha

    2017-09-01

    Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.

  8. Comparative evaluation of some commercially available brands of rifampacin tablets

    International Nuclear Information System (INIS)

    Shah, S.N.; Mahmood, K.; Uzair, M.; Rabbani, M.

    2009-01-01

    The objective of this study was to evaluate some commercially available brands of Rifampacin Tablets. In in- vitro release studies of physical parameters of tablet i.e. disintegration, dissolution rate, crushing strength, thickness and diameter, uniformity of weight and assay of the active ingredients of four brands of commercially available Rifampacin tablet i.e. A, B, C and D were performed. For this purpose, Dissolution rate was studied in phosphate buffer at pH 6.0, 6.5 and 7.4 using USP rotating basket at 100 rpm. The data was analyzed by Cube-Root law and calculated dissolution rate constant predicting in vitro behavior of the drug released from these preparations. In this particular case two types of dissolution mechanisms were founded; in first 20 minutes, the fast release phase and after 20 minutes the slow release phase. According to the degree of dissolution of D and B proved to be the best of the available commercial brands. (author)

  9. Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

    Science.gov (United States)

    Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

    2017-01-01

    In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

  10. Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP.

    Science.gov (United States)

    Ogunjimi, Abayomi Tolulope; Alebiowu, Gbenga

    2014-04-01

    This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr's index, Hausner's ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength-friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.

  11. Formulation and evaluation of fast dissolving tablets of cinnarizine using superdisintegrant blends and subliming material

    Directory of Open Access Journals (Sweden)

    Biswajit Basu

    2011-01-01

    Full Text Available The aim of this investigation was to develop fast dissolving tablet of cinnarizine. A combination of super disintegrants, i.e., sodium starch glycolate (SSG and crosscarmellose sodium (CCS were used along with camphor as a subliming material. An optimized concentration of camphor was added to aid the porosity of the tablet. A 3 2 full factorial design was applied to investigate the combined effect of two formulation variables: Amount of SSG and CCS. Infrared (IR spectroscopy was performed to identify the physicochemical interaction between drug and polymer. IR spectroscopy showed that there is no interaction of drug with polymer. In the present study, direct compression was used to prepare the tablets. The powder mixtures were compressed into tablet using flat face multi punch tablet machine. Camphor was sublimed from the tablet by exposing the tablet to vacuum drier at 60°C for 12 hours. All the formulations were evaluated for their characteristics such as average weight, hardness, wetting time, friability, content uniformity, dispersion time (DT, and dissolution rate. An optimized tablet formulation (F 9 was found to have good hardness of 3.30 ± 0.10 kg/cm 2 , wetting time of 42.33 ± 4.04 seconds, DT of 34.67 ± 1.53 seconds, and cumulative drug release of not less than 99% in 16 minutes.

  12. Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

    Science.gov (United States)

    Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

    2013-09-10

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Studies on Novel Pantoprazole and Cefuroxime Axetil Tablets for Site Specific Delivery.

    OpenAIRE

    Putta Rajesh Kumar

    2012-01-01

    In this study core in coat tablets containing enteric coated Pantaprazole (PP) core and Cefuroxime axetil (CA) floating type coat formulation as single unit prepared by compression coating method. The tablets were evaluated for their various pre-compression, compression characteristics, in vitro drug release kinetics and stability studies. The analytical estimation of drugs was found to be accurate and precise. The results of rheological characteristics indicated that, the powder beds of both...

  14. A INFLUÊNCIA DO Cissus chiclete na MECÂNICAS E LIBERTAÇÃO DE PROPRIEDADES PARACETAMOL COMPRIMIDOS - uma análise fatorial The influence of cissus gum on the mechanical and release properties of paracetamol tablets – a factorial analysis

    Directory of Open Access Journals (Sweden)

    ADETAYO O ADELEYE

    2010-06-01

    Full Text Available Os efeitos quantitativos de uma goma nova como a pasta nas propriedades mecânicas e da liberação de formulações da tabuleta do paracetamol foram avaliados usando um projeto 23 experimental factorial cheio. Goma de Cissus obtida do populnea Guill de Cissus. & Perr. (Vitaceae foi comparado com o gelatin oficial. Os efeitos do indivíduo e da interação do tipo de pasta, da concentração de fração da pasta e de embalagem na friabilidade, da força elástica, do índice da fratura frágil, do tempo da desintegração e da liberação da droga das tabuletas eram determinados. Mudar a pasta do gelatin à goma de Cissus conduziu a um aumento na friabilidade e a uma diminuição na força elástica, no BFI e nos parâmetros da liberação da droga. Concentração crescente da pasta de 2.0w/w a 4.0%w/w, e densidade relativa crescente de 0.80 a 0.90, conduzido para aumentar na tendência da laminação e na taxa de liberação das formulações. As tabuletas que contêm o gelatin tiveram uma força elástica mais elevada com mais baixa friabilidade, e uns tempos mais elevados da desintegração e da dissolução com mais tendência laminar quando comparadas com a goma de Cissus. Daqui, o cuidado deve ser recolhido escolhendo uma pasta apropriada para formulações da tabuleta no que diz respeito às características mecânicas e da liberação. O estudo sugere que a goma de Cissus seja preferida ao gelatin nas formulações da tabuleta que exibem a tendência tampar ou laminar ou nas formulações significadas para a liberação rápida da droga.The quantitative effects of a new gum, used as a binder, on the mechanical and release properties of paracetamol tablet formulations were analyzed in a 23 full factorial experiment. Cissus gum extracted from Cissus populnea Guill. & Perr. (Vitaceae was compared with official gelatin. The individual and interaction effects of type of binder, concentration of binder and packing fraction on the friability

  15. Modified geometry three-layered tablet as a platform for class II ...

    African Journals Online (AJOL)

    9,10]. Multi-layered tablets have showed a growing attention as a useful controlled release tool with multiple other applications such as drug combinations with reduced chance of interaction and/or inducing multi-drug release profiles in one.

  16. Formulation and in vitro evaluation of fast dissolving tablets of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Mangesh Machhindranath Satpute

    2013-12-01

    Full Text Available The demand for fast dissolving tablets has been growing during the last decade, especially for elderly and children who have swallowing difficulties. In the present work, fast dissolving tablets of metoprolol tartrate, were prepared using sodium starch glycolate, sodium croscarmellose and crospovidone as superdisintegrants, by the direct compression method. The tablets prepared were evaluated for various parameters including weight variation, hardness, friability, in vitro dispersion time, drug-polymer interaction, drug content water absorption ratio, wetting time, in vitro drug release, FTIR and DSC studies. The tablets prepared by the direct compression method had a weight variation in the range of 145 mg to 152 mg, which is below ± 7.5%, a hardness of 3.6 kg/cm² to 4.5 kg/cm², percentage friability of 0.46% to 0.73%, in vitro dispersion time of 18 s to 125 s, drug content uniformity of between 98.12% and 100.03%, a water absorption ratio of 67% to 87%, wetting time of 32 sec. to 64 sec., and an in vitro drug release of 53.92% - 98.82% within 15 min. The IR spectral analysis and DSC study showed no drug interaction with formulation additives of the tablet, and the formulations indicated no significant changes in hardness, friability, drug content or in vitro drug release. Fast dissolving tablets of metoprolol tartrate have enhanced dissolution and will lead to improved bioavailability and more effective therapy.

  17. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

    Science.gov (United States)

    Tahaineh, Linda M; Gharaibeh, Shadi F

    2012-08-01

    Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

  18. Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

    Science.gov (United States)

    Laparra, José Moisés; Haros, Monika

    2018-03-01

    Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

  19. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  20. The mechanism of diclofenac sodium release from non ...

    African Journals Online (AJOL)

    The mechanism of diclofenac sodium release from non-disintegrating bioadhesive tablets was studied. Diclofenac sodium was embedded in Carbopol 941 to produce bioadhesive granules, which were later, incorporated into a structure-forming material, paraffin wax. The tablets were formulated by pour moulding in a ...

  1. Formulation and In Vitro Evaluation of Release Retardant Diclofenac ...

    African Journals Online (AJOL)

    Development of release retardant matrix tablets of diclofenac sodium for 24 h by wet granulation technique using different combinations and ratios of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (sodium CMC), sodium alginate and cetostearyl alcohol was carried out. The tablets were evaluated ...

  2. Effect of Formulation Methods on the Mechanical and Release ...

    African Journals Online (AJOL)

    The mechanical properties of the tablets were assessed using the crushing strength (CS), friability(F) and crushing strength-friability ratio (CSFR) of the tablets, while drug release properties were assessed using disintegration time and dissolution profile. The granules possessed better flow properties than the powder ...

  3. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    International Nuclear Information System (INIS)

    Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye Lin; Yun, Jimmy

    2010-01-01

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  4. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    Energy Technology Data Exchange (ETDEWEB)

    Heng, Desmond [Institute of Chemical and Engineering Sciences (Singapore); Ogawa, Keiko [Nitto Denko Co. Ltd., Medical Division (Japan); Cutler, David J.; Chan, Hak-Kim, E-mail: kimc@pharm.usyd.edu.a [University of Sydney, Advanced Drug Delivery Group, Faculty of Pharmacy, A15 (Australia); Raper, Judy A. [University of Wollongong, Vice Chancellor' s Unit (Australia); Ye Lin [University of Sydney, School of Aerospace, Mechanical and Mechatronic Engineering (Australia); Yun, Jimmy [Nanomaterials Technology Pty. Ltd. (Singapore)

    2010-06-15

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 {+-} 2.7% to 72.3 {+-} 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  5. Pure drug nanoparticles in tablets: what are the dissolution limitations?

    Science.gov (United States)

    Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

    2010-06-01

    There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

  6. Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.

    Science.gov (United States)

    Kassem, Mohamed A A; Elmeshad, Aliaa N; Fares, Ahmed R

    2014-03-10

    This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(₅₀%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

    Science.gov (United States)

    Kim, Kyu-Nam; Yang, Sung-Won; Kim, Hyunil; Kwak, Seong Shin; Kim, Young-Sang; Cho, Doo-Yeoun

    2018-01-01

    CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state. © 2017, The American College of Clinical Pharmacology.

  8. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    Science.gov (United States)

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. How do tablet properties influence swallowing behaviours?

    Science.gov (United States)

    Yamamoto, Shinya; Taniguchi, Hiroshige; Hayashi, Hirokazu; Hori, Kazuhiro; Tsujimura, Takanori; Nakamura, Yuki; Sato, Hideaki; Inoue, Makoto

    2014-01-01

    Behavioural performance of tablet swallowing was evaluated with different tablet conditions in terms of size, number and surface coating. Four different types of tablets were prepared: small or large, and with or without a surface coating. Fourteen normal male adults were instructed to swallow the prepared tablets with 15 ml of water. The number of tablets in one trial was changed from one to three. To evaluate swallowing and tablet transport, electromyographic activity was recorded in the left suprahyoid muscles, and videofluorographic images were examined. All tablet conditions (size, number and surface coating) affected the swallowing performance in terms of total number of swallows, electromyographic burst patterns and location of remaining tablets. Increases in the size and number of tablets increased the number of swallows and electromyographic burst area and duration. In addition, all of these parameters increased while swallowing tablets without a coating compared with tablets with a coating. Location of the remaining tablets was mainly within the mouth. This study only clarified the normal pattern of tablet swallowing under several conditions in healthy subjects, but the results may facilitate comprehensive evaluation and treatment planning in terms of administering medication to dysphagic patients. © 2013 Royal Pharmaceutical Society.

  10. Galileo's Telescopy and Jupiter's Tablet

    Science.gov (United States)

    Usher, P. D.

    2003-12-01

    A previous paper (BAAS 33:4, 1363, 2001) reported on the dramatic scene in Shakespeare's Cymbeline that features the descent of the deity Jupiter. The paper suggested that the four ghosts circling the sleeping Posthumus denote the four Galilean moons of Jupiter. The god Jupiter commands the ghosts to lay a tablet upon the prone Posthumus, but says that its value should not be overestimated. When Posthumus wakens he notices the tablet, which he calls a "book." Not only has the deity's "tablet" become the earthling's "book," but it appears that the book has covers which Posthumus evidently recognizes because without even opening the book he ascribes two further properties to it: rarity, and the very property that Jupiter had earlier attributed, viz. that one must not read too much into it. The mystery deepens when the Jovian gift undergoes a second metamorphosis, to "label." With the help of the OED, the potentially disparate terms "tablet," "book," and "label," may be explained by terms appropriate either to supernatural or worldly beings. "Tablet" may recognize the Mosaic artifact, whereas "book" and "label" are probably mundane references to Galileo's Sidereus Nuncius which appeared shortly before Cymbeline. The message of the Olympian god indicates therefore that the book is unique even as its contents have limited value. The first property celebrates the fact that Galileo's book is the first of its kind, and the second advises that all results except the discovery of Jupiter's moons have been reported earlier, in Hamlet.

  11. Continuous passive motion and physical therapy (CPM) versus physical therapy (PT) versus delayed physical therapy (DPT) after surgical release for elbow contractures; a study protocol for a prospective randomized controlled trial.

    Science.gov (United States)

    Viveen, Jetske; Doornberg, Job N; Kodde, Izaak F; Goossens, Pjotr; Koenraadt, Koen L M; The, Bertram; Eygendaal, Denise

    2017-11-22

    The elbow is prone to stiffness after trauma. To regain functional elbow motion several conservative- and surgical treatment options are available. Conservative treatment includes physical therapy, intra-articular injections with corticosteroids and a static progressive or dynamic splinting program. If conservative treatment fails, an operative release of the posttraumatic stiff elbow is often performed. The best Evidence-Based rehabilitation protocol for patients after an operative release is unknown to date and differs per surgeon, hospital and country. Options include early- or delayed motion supervised by a physical therapist, immediate continuous passive motion (CPM), (night) splinting and a static progressive or dynamic splinting program. The SET-Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled trial. The primary objective of this study is to compare the active Range of Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between three groups. The first group will receive in-hospital CPM in combination with early motion Physical Therapy (PT) supervised by a physical therapist, the second group will receive only in-hospital early motion PT supervised by a physical therapist and the third group will receive outpatient supervised PT from postoperative day seven till ten. Secondary outcome measures will be Patient Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for Epidemiological Studies Depression Scale Revised (CESD-R) and the Work Rehabilitation Questionnaire (WORQ) for the upper limb. A successful completion of this trial will provide evidence on the best rehabilitation protocol in order to (re)gain optimal motion after surgical release of the stiff elbow

  12. Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

    Science.gov (United States)

    Ha, Jung-Myung; Seo, Jeong-Woong; Kim, Su-Hyeon; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

    2017-11-01

    The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300 mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.

  13. Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

    Science.gov (United States)

    Bokser, L; Schally, A V

    1988-10-01

    Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

  14. Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

    Science.gov (United States)

    Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

    2016-06-01

    A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

  15. Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

    Directory of Open Access Journals (Sweden)

    Hussain Amjad

    2016-06-01

    Full Text Available A novel mucoadhesive buccal tablet containing flurbiprofen (FLB and lidocaine HCl (LID was prepared to relieve dental pain. Tablet formulations (F1-F9 were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC and sodium alginate (SA. The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release, which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

  16. Modelling delays in pharmacokinetics

    International Nuclear Information System (INIS)

    Farooqi, Z.H.; Lambrecht, R.M.

    1990-01-01

    Linear system analysis has come to form the backbone of pharmacokinetics. Natural systems usually involve time delays, thus models incorporating them would be an order closer approximation to the real world compared to those that do not. Delays may be modelled in several ways. The approach considered in this study is to have a discrete-time delay dependent rate with the delay respresenting the duration between the entry of a drug into a compartment and its release in some form (may be as a metabolite) from the compartment. Such a delay may be because of one or more of several physiological reasons, like, formation of a reservoir, slow metabolism, or receptor binding. The mathematical structure this gives rise to is a system of delay-differential equations. Examples are given of simple one and two compartment systems with drugs like bumetanide, carbamazepine, and quinolone-caffeine interaction. In these examples generally a good fit is obtained and the suggested models form a good approximation. 21 refs., 6 figs

  17. Principles of Tablet Computing for Educators

    Science.gov (United States)

    Katzan, Harry, Jr.

    2015-01-01

    In the study of modern technology for the 21st century, one of the most popular subjects is tablet computing. Tablet computers are now used in business, government, education, and the personal lives of practically everyone--at least, it seems that way. As of October 2013, Apple has sold 170 million iPads. The success of tablets is enormous and has…

  18. Touch Screen Tablets and Emergent Literacy

    Science.gov (United States)

    Neumann, Michelle M.; Neumann, David L.

    2014-01-01

    The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…

  19. 21 CFR 520.812 - Enrofloxacin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No...

  20. TabletGaze: Unconstrained Appearance-based Gaze Estimation in Mobile Tablets

    OpenAIRE

    Huang, Qiong; Veeraraghavan, Ashok; Sabharwal, Ashutosh

    2015-01-01

    We study gaze estimation on tablets, our key design goal is uncalibrated gaze estimation using the front-facing camera during natural use of tablets, where the posture and method of holding the tablet is not constrained. We collected the first large unconstrained gaze dataset of tablet users, labeled Rice TabletGaze dataset. The dataset consists of 51 subjects, each with 4 different postures and 35 gaze locations. Subjects vary in race, gender and in their need for prescription glasses, all o...

  1. Using iPad Tablets for Self-modeling with Preschoolers: Videos versus Photos

    Science.gov (United States)

    McCoy, Dacia M.; Morrison, Julie Q.; Barnett, Dave W.; Kalra, Hilary D.; Donovan, Lauren K.

    2017-01-01

    As technology becomes more accessible and acceptable in the preschool setting, teachers need effective strategies of incorporating it to address challenging behaviors. A nonconcurrent delayed multiple baseline design in combination with an alternating treatment design was utilized to investigate the effects of using iPad tablets to display video…

  2. Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

    Science.gov (United States)

    Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

    2016-02-29

    Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.

    Science.gov (United States)

    Berner-Strzelczyk, Aneta; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2006-01-01

    The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.

  4. Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil.

    Science.gov (United States)

    Wasnik, Mangesh N; Godse, Rutika D; Nair, Hema A

    2014-05-01

    Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson's disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson's disease. Polycarbophil-cysteine (PCP-cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP-cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP-cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP-cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson's disease.

  5. Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

    Science.gov (United States)

    Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

    2017-02-01

    This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA ® Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

  6. Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology.

    Science.gov (United States)

    McConville, Christopher; Major, Ian; Devlin, Brid; Brimer, Andrew

    2016-07-01

    Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. Development of tablets containing semipurified extract of guaraná (Paullinia cupana

    Directory of Open Access Journals (Sweden)

    Traudi Klein

    2012-12-01

    Full Text Available This study evaluated the technological feasibility of producing a semipurified extract of guaraná (Paullinia cupana Kunth, Sapindaceae in tablet form, using a direct-compression process. Maltodextrin and gum arabic were used to produce the extract microparticles, in order to protect the microparticles against such factors as temperature, oxidation, and humidity. Using pharmacopoeial methodologies, technological and physicochemistry tests (determination of residual moisture, of bulk and tapped density, Hausner ratio, compressibility and compactibility index, appearance, mean weight, hardness, friability, disintegration time, determination of EPA amount in tablets and in vitro release profile were conducted. The formulation containing 200 mg of microparticles, 170 mg microcrystalline cellulose, and 10 mg lactose gave the best results in terms of hardness (116 N, friabilility (0.28%, mean weight (0.3821 g, and disintegration time (25 min for a tablet designed for oral administration. The results met pharmacopoeial specifications, and the tablets are suitable for oral administration.

  11. Delayed Ejaculation

    Science.gov (United States)

    ... cases, it is due to a combination of physical and psychological concerns. Psychological causes of delayed ejaculation include: Depression, anxiety or other mental health conditions Relationship problems due to stress, poor communication ...

  12. Delayed growth

    Science.gov (United States)

    ... Slow rate of growth; Retarded growth and development; Growth delay Images Toddler development References Cooke DW, Divall SA, Radovick S. Normal and aberrant growth in children. In: Melmed S, Polonsky KS, Larsen PR, ...

  13. Learning, Tablet, Culture-Coherence?

    Science.gov (United States)

    Norqvist, Lars

    2016-01-01

    This paper presents understandings of learning in schools where Internet-enabled Information and Communication Technologies (ICTs) are taken for granted. The context is a full-scale 1:1 tablet project in Danish municipality schools where this study bring forward expressions of learning from one class (12-13 year old children) in order to offer…

  14. Stage control of tablets manufacturing

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2014-08-01

    Full Text Available Today in Ukraine tuberculosis is the wide-spread infectious disease causing the death in most cases; about 700 thousand persons are suffering from it. In Ukraine epidemic of tuberculosis is progressing and spreading. In spite of all protective measures three inhabitants of our country contract tuberculosis per hour, every hour one patient dies and in common about 1.5% of the population is ill with tuberculosis. Isoniazid is antituberculous drug of the first line and it is the most effective one. Chemotherapy of tuberculosis requests long-lasting administration of antituberculous drugs that causes high risk of side effects. To prevent or lessen side effects of antituberculous medicines antioxidants use in complex therapy is perspective. Fulfilled investigations showed efficacy of combining two medical substances – isoniazid andthiotriazolin – in one dosage form. Objective.The aim of our investigation is working out the methods of standardization, in particularquantitative determination of isoniazid andthiotriazolin content in tablet mass by high-performance liquid chromatography (HPLC. Materials and Methods.During in-process investigations combined tableted remedy containing isoniazid andthiotriazolin and proper amount of adjuvants has been developed (it contains active substances isoniazid – 0.2 g,thiotriazolin – 0.05 g and adjuvants up to the 0.4 g of the tablet. During stage control of tablets manufacturingspecial attention is paid to the control of tablet mass quality. Especially it concerns quantitative determination of active substances in it. More and more attention is paid to modern physical-chemical methods of standardization in up-to-date analysis of drug products, such as ultraviolet spectrometry, high-performance liquid chromatography (HPLC etc. In previous scientific investigations we proved the possibility of standardization of active substances artificial compound by HPLC method and optimal conditions of analysis performing

  15. Formulation and in vitro and in vivo evaluation of film-coated montelukast sodium tablets using Opadry® yellow 20A82938 on an industrial scale

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2013-02-01

    Full Text Available Abdel Naser Zaid,1 Salam Natur,2 Aiman Qaddumi,2 Abeer Abu Ghoush11Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Pharmacare PLC, Ramallah, PalestinePurpose: The aim of this study was to formulate stable film-coated montelukast sodium (MS tablets using Opadry® yellow 20A82938 (Montikast® tablets and to evaluate their in vitro and in vivo release profile.Methods: MS core tablets were manufactured using a direct compression method. Opadry yellow 20A82938 aqueous coating dispersion was used as the film-coating material. Dissolution of the film-coated tablets was tested in 900 mL of 0.5% sodium lauryl sulfate solution and the bioequivalence of the tablets was tested by comparing them with a reference formulation – Singulair® tablets. In vitro–in vivo correlation was evaluated. The stability of the obtained film-coated tablets was evaluated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines.Results: The efficiency of the film coating was determined by subjecting the coated tablets to gastric pH and drug release was analyzed using high-performance liquid chromatography. The coated tablets had no obvious defects. MS release met the study criterion of not less than 80% dissolved after 30 minutes in 0.5% sodium lauryl sulfate solution. Statistical comparison of the main pharmacokinetic parameters clearly indicated no significant difference between test and reference in any of the calculated pharmacokinetic parameters. Level A correlation between in vitro drug release and in vivo absorption was found to be satisfactory.Conclusion: These findings suggest that aqueous film coating with Opadry yellow 20A82938 is an easy, reproducible, and economical approach for preparing stable MS film-coated tablets without affecting the drug-release characteristics.Keywords: coating, stability, aqueous

  16. Pharmaceutical equivalence of metformin tablets with various binders

    Directory of Open Access Journals (Sweden)

    L. C. Block

    2009-01-01

    Full Text Available

    Metformin hydrochloride is a high-dose drug widely used as an oral anti-hyperglycemic agent. As it is highly crystalline and has poor compaction properties, it is difficult to form tablets by direct compression. The aim of this study was to develop adequate metformin tablets, pharmaceutically equivalent to the reference product, Glucophage® (marketed as Glifage® in Brazil. Metformin 500mg tablets were produced by wet granulation with various binders (A = starch, B = starch 1500®, C = PVP K30®, D = PVP K90®. The tablets were analyzed for their hardness, friability, disintegration, dissolution, content uniformity and dissolution profile (basket apparatus at 50 rpm, pH 6.8 phosphate buffer. The 4 formulations, F1 (5% A and 5% C, F2 (5% B and 5% C, F3 (10% C and F4 (5% D, demonstrated adequate uniformity of content, hardness, friability, disintegration and total drug dissolution after 30 minutes (F1, F2 and F4, and after 60 minutes (F3. The drug release time profiles fitted a Higuchi model (F1, F2 and F3, similarly to the pharmaceutical reference, or a zero order model (F4. The dissolution efficiency for all the formulations was 75%, except for F3 (45%. F1 and F2 were thus equivalent to Glifage®. Keywords: dissolution; metformin; tablet; binder; pharmaceutical equivalence

  17. Quantitative Appearance Inspection for Film Coated Tablets.

    Science.gov (United States)

    Yoshino, Hiroyuki; Yamashita, Kazunari; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.

  18. Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

    Science.gov (United States)

    Wren, S A C; Alhusban, F; Barry, A R; Hughes, L P

    2017-08-30

    The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1 H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  20. Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets.

    Science.gov (United States)

    Al-Tabakha, Moawia M; Fahelelbom, Khairi M S; Obaid, Dana Emad Eddin; Sayed, Sadik

    2017-05-20

    Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market.

  1. Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing.

    Science.gov (United States)

    Li, Qijun; Guan, Xiaoying; Cui, Mengsuo; Zhu, Zhihong; Chen, Kai; Wen, Haoyang; Jia, Danyang; Hou, Jian; Xu, Wenting; Yang, Xinggang; Pan, Weisan

    2018-01-15

    Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design. Copyright © 2017. Published by Elsevier B.V.

  2. Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist.

    Science.gov (United States)

    Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

    2012-10-01

    The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 2(3) full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug-excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease.

  3. Sustained Release of a Water-Soluble Drug from Directly ...

    African Journals Online (AJOL)

    Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

  4. Formulation and evaluation of bilayer tablets of metoclopramide hydrochloride and diclofenac sodium.

    Science.gov (United States)

    Gattani, Surendra G; Khabiya, Sohan S; Amrutkar, Jitendra R; Kushare, Sachin S

    2012-01-01

    The main objective of the present research work was to develop a bilayer tablet of metoclopramide hydrochloride (MTH) and diclofenac sodium (DS) in separate layers to avoid incompatibility and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine headaches. MTH and DS were formulated as immediate and sustained release layers respectively. In vitro dissolution kinetic studies of an optimized (D10) batch of DS in both sustained release layer and bilayer tablet forms show good linearity of regression coefficient 0.9773 (first order equation). The results reveal that an optimized immediate release layer (M5) of MTH and a sustained release layer (D10) of DS might be suitable for the treatment of migraine by sequential release of the two drugs in a bilayer tablet. Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.

  5. 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.

  6. A tandem queue with delayed server release

    NARCIS (Netherlands)

    Nawijn, W.M.

    1997-01-01

    We consider a tandem queue with two stations. The rst station is an s-server queue with Poisson arrivals and exponential service times. After terminating his service in the rst station, a customer enters the second station to require service at an exponential single server, while in the meantime he

  7. Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

    Science.gov (United States)

    Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

    2008-05-01

    Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

  8. Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

    Science.gov (United States)

    Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

    2015-05-01

    Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

  9. Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

    Science.gov (United States)

    Sadeghi, Mozhgan; Hemmati, Salar; Hamishehkar, Hamed

    2016-01-01

    Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

  10. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    Science.gov (United States)

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the

  11. Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets.

    Science.gov (United States)

    Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Yang, Chan; Cui, Xianglong; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules' properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). By analyzing the loadings plots and variable importance in the projection indexes, the granule particle sizes and the minimal punch tip separation distance in tableting were identified as critical process parameters. Additionally, the MBPLS model suggested that the lubrication time in the final blending was also important in predicting tablet quality attributes. From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet.

  12. Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

    Science.gov (United States)

    Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Yang, Chan; Cui, Xianglong; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules’ properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). By analyzing the loadings plots and variable importance in the projection indexes, the granule particle sizes and the minimal punch tip separation distance in tableting were identified as critical process parameters. Additionally, the MBPLS model suggested that the lubrication time in the final blending was also important in predicting tablet quality attributes. From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet. PMID:27932865

  13. Colour Reproduction on Tablet Devices

    Directory of Open Access Journals (Sweden)

    Vladimir Zorić

    2014-07-01

    Full Text Available With the advent of Internet and mobile devices client services and other print production are migrating more and more to online platforms. In a recent technology changeover it is obvious that there is growing number of printers as well need from the customers for the print service providers to expand their business to online and mobile platforms. With this technological transition there are some open questions regarding the possibilities of using the tablet devices for colour soft proofing and other colour related operations. As a display devices on a hardware level there are large similarities with the desktop display devices but the operating systems which are driving them are not yet colour smart. There have been some initial attempts to characterize the colour reproduction on this type of devices and find a possibility of using them not just for information content but also for colour managed content. In this study we have tested several tablets (Apple iPad2,Asus Transformer TF101, Samsung Galaxy Tab 1 with different display and OS technology and tested a software which is intended for colour managed viewing of the reproduction. We have measured the colour reproduction of the tablets with the digital version of the GretagMacbeth ColorChecker card and have calculated the colour differences between the colour chart data and the displayed data. We have calibrated the Ipad2 with the only existing colour management tool the Spyder Gallery and we have also tested the chart display with and without the colour correction of the software. We have found that there are differences in the colour reproduction of the display technologies and that the possibilities of a real colour managed workflow has yet to be resolved on the OS level of tablet and mobile devices

  14. Preparation and Evaluation of Hot-Melt Extruded Patient-Centric Ketoprofen Mini-Tablets.

    Science.gov (United States)

    Alshetaili, Abdullah S; Almutairy, Bjad K; Tiwari, Roshan V; Morott, Joseph T; Alshehri, Sultan M; Feng, Xin; Alsulays, Bader B; Park, Jun-Bom; Zhang, Feng; Repka, Michael A

    2016-01-01

    Bitter tasting drugs represent a large portion of active pharmaceutical ingredients. Mini-tablets are specifically designed for patients with difficulty in swallowing particular in young children up to 10 years of age, geriatric patients and patients with esophagitis. The present study was aimed to prepare, taste-masked mini-tablets, which are easily swallowed dosage forms, primarily to be used by pediatric and geriatric patients. Ketoprofen (10%-50% w/w) and Eudragit® EPO were blended and extruded with a 5-mm strand die and cut into consistent mini-tablets by using an adapted downstream pelletizer. Differential scanning calorimetry and polarized light microscopy-hot stage microscopy studies confirmed that the binary mixtures were miscible under the employed extrusion temperatures. In-vitro release studies showed that drug release was less than 0.5% within the first 2 min in simulated salivary fluid (pH 6.8) and more than 90% in the first 20 min in gastric media (pH 1.0). The results of the electronic tongue analysis were well correlated with the drug release profile of the mini-tablets in the artificial saliva. Scanning electron microscopy revealed no cracks on the surface of the minitablets, confirming that the mini-tablets were compact solids. Chemical imaging confirmed the uniform distribution of ketoprofen inside the polymer matrices. Eudragit® EPO containing ketoprofen at various drug loads were successfully melt extruded into tastedmasked mini-tablets. The reduced drug release at salivary pH correlated well with Astree e-Tongue studies for taste masking efficiency.

  15. Developmental delay

    Science.gov (United States)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  16. Formulation and Characterization of Matrix and Triple-Layer matrix tablets for Controlled Delivery of Metoprolol tartrate

    OpenAIRE

    Izhar Ahmed Syed; Lakshmi Narsu Mangamoori; Yamsani Madhusudan Rao

    2011-01-01

    In the present study matrix and triple layer matrix tablets of metoprolol tartrate were formulated by using xanthan gum as the matrix forming agent and Sodium Carboxy Methyl Cellulose (Na CMC) as barrier layers. The prepared tablets were analysed for their hardness, friability, drug content and in-vitro drug release studies. Marked differences in dissolution characteristics of (M3) and (M3L3) were observed and showed a significant difference statistically. Mean dissolution time (MDT) for M3 a...

  17. 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

  18. Can Tablet Computers Enhance Faculty Teaching?

    Science.gov (United States)

    Narayan, Aditee P; Whicker, Shari A; Benjamin, Robert W; Hawley, Jeffrey; McGann, Kathleen A

    2015-06-01

    Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.

  19. Specifications development for "Karbatril" codenamed tablets

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2017-08-01

    Full Text Available Introduction. According to current legislation of Ukraine the specifications of tablets include the following indicators: description, identification, average weight, disintegration and assay. The aim of the study. The development of specifications and project of quality control methods for "Karbatril" codenamed tablets. Materials and methods. During the study we analyzed 6 series of tablets "Karbatril." For the description, identification, determination of the average mass, disintegration, active ingredients quantify of "Karbatril" codenamed tablets we used appropriate methods and instruments. Results and discussion. Tablets "Karbatril" were analyzed for the following parameters: - Overview - Tablets white or nearly white; - Average weight - during the study the average weight of 6 series of obtained tablets ranged from 339,0 mg to 369,9 mg according to SPU from 337,0 mg to 373,0 mg; - Disintegration – according to SPU the disintegration for tablet without shell shall not exceed 15 min. Analyzed tablets disintegrated in the period from 5 to 10 minutes; - Identification and quantification of the active ingredients of tablets were conducted using modified HPLC methods. During the identification obtained chromatograms show compliance with SPU. In quantitative determination of the active ingredients content in "Karbatril" codenamed tablets we found carbamazepine from 148.18 mg to 150.19 mg, thiotriazoline - from 98.93 mg to 99.71 mg. This data is consistent to SPU which regulates content of carbamazepine - 150 mg ± 7,5%, thiotriazoline - 100 mg ± 10%. Conclusions. This study has developed specification for "Karbatril" codenamed tablets and also methods of HPLC qualitative and quantitative determination of active ingredients. In the specification the following parameters are included: description, identification, average weight, disintegration and assay. The study drafted quality control methods which are planned to be later offered to the

  20. Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

    OpenAIRE

    Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.

    2011-01-01

    Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala p...

  1. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    ZHANG Yang

    2013-02-01

    Full Text Available A novel non-enzymatic glucose sensor was developed by electrodepositing copper film onto the graphene(GR substrate.The morphologies and structures of the nanocomposites were characterized by field emission scanning electron microscope (FESEM.The electrochemical performances of the Cu/GR nanocomposite film were investigated.The Cu/GR nanocomposite film showed good electrocatalytic activity towards glucose oxidation in alkaline solution.The Cu/GR nanocomposite film-based sensor displayed a linear concentration range from 8×10-6 to 9.4×10-4 mol/L with the sensitivity of 0.225 A·L·mol-1 and the detection limit (S/N=3 of 2.5 μmol/L for the detection of glucose.With an enhanced electrocatalytic property,high sensitivity and good stability.The as-prepared sensor is promising for the future development of nonenzymatic sensors.

  2. vitro Release of Saraca indica Caesalpiniaceae Bark Powder Tablets

    African Journals Online (AJOL)

    ... author: Email: onlyusatya@gmail.com, singh.satyaprakash@rediffmail.com; ... the literature on the optimization of .... Crack theory can be used to develop a ..... Practice of Industrial Pharmacy. ... application of percolation theory to powder.

  3. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    Erah

    phenomenon. At the molecular level, it involves .... mark with simulated gastric fluid (SGF, pH. 1.2). ... erosion of the polymeric chain while anomalous .... appeared at 186.7oC disappeared while a ... substances and excipients on gel dynamics.

  4. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Development and evaluation of gastroretentive floating tablets of an antidepressant drug by thermoplastic granulation technique

    Directory of Open Access Journals (Sweden)

    Harshal Ashok Pawar

    2014-06-01

    Full Text Available The present study was undertaken with an aim to formulate, develop and evaluate gastroretentive floating tablets of an antidepressant drug, Venlafaxine HCl (hydrochloride, which release the drug in a sustained manner over a period of 24 h. Three different hydrophobic retardants namely hydrogenated cottonseed oil, carnauba wax, cetyl alcohol and a hydrophilic polymer Methocel® (hydroxy propyl methyl cellulose (HPMC K15M were used in different combinations at different ratios for the preparation of tablets. The tablets were prepared by Hot Melt or Thermoplastic granulation method and evaluated for tablet thickness, hardness, weight variation, friability, floating lag time and in vitro drug release. Formulation F8 with hydrophilic polymer (Methocel® K15M and hydrophobic retardant (carnauba wax in the ratio 1:2.6 (approx. was considered as an optimized formulation. The optimized formulation showed satisfactory sustained drug release and remained buoyant on the surface of the medium for more than 24 h and its release profile was comparable with the marketed formulation (VENTAB-XL 37.5. It can also be concluded that floating drug delivery system of Venlafaxine HCl can be successfully formulated as an approach to increase gastric residence time and thereby improving its bioavailability.

  6. Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions

    NARCIS (Netherlands)

    Van Drooge, D.J.; Hinrichs, W.L.J.; Frijlink, H.W.

    2004-01-01

    In this study, anomalous dissolution behaviour of tablets consisting of sugar glass dispersions was investigated. The poorly aqueous soluble diazepam was used as a lipophilic model drug. The release of diazepam and sugar carrier was determined to study the mechanisms governing dissolution behaviour.

  7. Terbutaline depot tablets in childhood asthma. A double-blind controlled study

    DEFF Research Database (Denmark)

    Foged, N; Høst, A; Ljungholm, K

    1985-01-01

    Thirty children 8-13 years old, with perennial asthma and with a reversibility of greater than or equal to 20% in lung function (FEV1) were given a sustained-release preparation of terbutaline sulphate 5 mg twice a day and ordinary tablets 2.5 mg three times a day; each treatment lasted 1 week...

  8. Development and in-vitro Evaluation of Once Daily Tablet Dosage ...

    African Journals Online (AJOL)

    Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS,. Pharm Sci Tech 2006; 7: 1-9. 6. Kumar R, Patil S, Patil MB, Patil SR, Paschapur MS. Design and In vitro Evaluation ...

  9. Tablet surface characterisation by various imaging techniques

    DEFF Research Database (Denmark)

    Seitavuopio, Paulus; Rantanen, Jukka; Yliruusi, Jouko

    2003-01-01

    The aim of this study was to characterise tablet surfaces using different imaging and roughness analytical techniques including optical microscopy, scanning electron microscopy (SEM), laser profilometry and atomic force microscopy (AFM). The test materials compressed were potassium chloride (KCl......) and sodium chloride (NaCl). It was found that all methods used suggested that the KCl tablets were smoother than the NaCl tablets and higher compression pressure made the tablets smoother. Imaging methods like optical microscopy and SEM can give useful information about the roughness of the sample surface...

  10. Application of mixture experimental design in the formulation and optimization of matrix tablets containing carbomer and hydroxy-propylmethylcellulose.

    Science.gov (United States)

    Petrovic, Aleksandra; Cvetkovic, Nebojsa; Ibric, Svetlana; Trajkovic, Svetlana; Djuric, Zorica; Popadic, Dragica; Popovic, Radmila

    2009-12-01

    Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.

  11. Clinical pharmacokinetic study for the effect of glimepiride matrix tablets developed by quality by design concept.

    Science.gov (United States)

    Ahmed, Tarek A; Suhail, Mohammad A A; Hosny, Khaled M; Abd-Allah, Fathy I

    2018-01-01

    Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP). Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients. Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products. Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6-7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4 ng/mL), longer time to reach maximum plasma concentration (4 h) and longer t 1/2 (7.236 h) compared to other groups. Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.

  12. The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants

    Science.gov (United States)

    Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

    2015-01-01

    Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440–3450, 2015 PMID:26073446

  13. The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants.

    Science.gov (United States)

    Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

    2015-10-01

    Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440-3450, 2015. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

    Science.gov (United States)

    Ikeuchi-Takahashi, Yuri; Kobayashi, Ayaka; Onishi, Hiraku

    2017-06-01

    Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets u