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Sample records for granule dosage form

  1. Advances in solid dosage form manufacturing technology.

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

  2. [Pharmaceutical advice concerning different pharmaceutical dosage forms].

    Szakonyi, Gergely; Zelkó, Romána

    2010-01-01

    The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

  3. Amorphous drugs and dosage forms

    Grohganz, Holger; Löbmann, K.; Priemel, P.

    2013-01-01

    The transformation to an amorphous form is one of the most promising approaches to address the low solubility of drug compounds, the latter being an increasing challenge in the development of new drug candidates. However, amorphous forms are high energy solids and tend to recry stallize. New...... formulation principles are needed to ensure the stability of amorphous drug forms. The formation of solid dispersions is still the most investigated approach, but additional approaches are desirable to overcome the shortcomings of solid dispersions. Spatial separation by either coating or the use of micro-containers...... before single molecules are available for the formation of crystal nuclei, thus stabilizing the amorphous form....

  4. Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

    Kristó, Katalin; Pintye-Hódi, Klára

    2013-02-01

    The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

  5. The characteristics of novel dosage forms

    Milić-Aškrabić Jela

    2003-01-01

    Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

  6. [Oral films as perspective dosage form].

    Walicová, Veronika; Gajdziok, Jan

    Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

  7. Microbial quality of some herbal solid dosage forms

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

  8. New applications to computerized tomography: analysis of solid dosage forms produced by pharmaceutical industry

    Oliveira Junior, Jose Martins de; Martins, Antonio Cesar Germano

    2009-01-01

    Full text: In recent years, computerized tomography (CT) has been used as a new probe to study solid dosage forms (tablets) produced by pharmaceutical industry. This new approach to study tablet and powder, or granulation, properties used in pharmaceutical industry is very suitable. First because CT can generate information that traditional technologies used in this kind of analysis can not, such as, density distribution of internal structures and tablet dimensions, pore size distribution, particle shape information, and also investigation of official and unofficial (counterfeit) copies of solid dosage forms. Second because CT is a nondestructive technique, allowing the use of tablets or granules in others analysis. In this work we discus how CT can be used to acquire and reconstruct internal microstructure of tablets and granules. CT is a technique that is based on attenuation of X-rays passing through matter. Attenuation depends on the density and atomic number of the material that is scanned. In this work, a micro-CT X-ray scanner (manufactured by the group of Applied Nuclear Physics at University of Sorocaba) was used to obtain three-dimensional images of the tablets and granules for nondestructive analysis. These images showed a non uniform density distribution of material inside some tablets, the morphology of some granules analyzed, the integrity of the liquid-filled soft-gelatin capsule and so on. It could also be observed that the distribution of different constituents presents an osmotic controlled-release dosage form. The present work shows that it is possible to use X-ray microtomography to obtain useful qualitative and quantitative information on the structure of pharmaceutical dosage forms. (author)

  9. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  10. 21 CFR 520.1696 - Penicillin oral dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  11. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

  12. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

  13. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

  14. 21 CFR 520.45 - Albendazole oral dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  15. Automatic identification and normalization of dosage forms in drug monographs

    2012-01-01

    Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

  16. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  17. Antioxidant activity evaluation of new dosage forms as vehicles for dehydrated vegetables.

    Romero-de Soto, María Dolores; García-Salas, Patricia; Fernández-Arroyo, Salvador; Segura-Carretero, Antonio; Fernández-Campos, Francisco; Clares-Naveros, Beatriz

    2013-06-01

    A dehydrated vegetables mixture loaded in four pharmaceutical dosage forms as powder, effervescent granulate, sugar granulate and gumdrops were investigated for their antioxidant capacity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging capacity assay, oxygen radical absorbance capacity assay and ferric reducing antioxidant potential assay. Total phenolic content of dehydrated vegetables powder mixture was also measured by the Folin-Ciocalteu method, so as to evaluate its contribution to their total antioxidant function. The effect of different temperatures on stability of these systems after 90 days storage was also evaluated. These formulations presented strong antioxidant properties and high phenolic content (279 mg gallic acid equivalent/g of sample) and thus could be potential rich sources of natural antioxidants. Antioxidant properties differed significantly among selected formulations (p forms are new and innovative approach for vegetable intakes in population with special requirements providing an improvement in the administration of vegetables and fruits.

  18. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Preparation and characterization of solid oral dosage forms containing soy isoflavones

    Stela R. de Oliveira

    2013-02-01

    Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

  20. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    2011-09-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  1. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    2012-01-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  2. 76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

    2011-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  3. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    2011-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  4. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  5. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    2010-11-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  6. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    2011-12-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  7. Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

    Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

    2004-01-01

    A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

  8. 21 CFR 520.1448 - Monensin oral dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... distance the spots travel from the starting line divided by the distance the solvent front travels from the...

  9. Formulation of Croton penduliflorus seed into tablet dosage form ...

    Formulation of Croton penduliflorus seed into tablet dosage form. GC Onunkwo. Abstract. No Abstract. Global Journal of Medical Sciences Vol. 5(1) 2006: 29-33. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/gjms.v5i1.10145.

  10. Formulation and evaluation of tablet dosage form of Hunteria ...

    The present study was aimed at formulating and evaluating tablet dosage form of Hunteria umbellata (HU) seed aqueous and purified extracts. HU seeds were dried, pulverized and the powder macerated in water to obtain aqueous extract, while alkaloidal extraction process was used to obtain purified extract. Extracts ...

  11. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  12. Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

    Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

  13. THE FACTORS FORMING QUALITY OF GRANULATED SUGAR

    N. G. Kulneva

    2015-01-01

    Full Text Available Sugar, with good taste and high caloric, is one of the most popular human food. Consumers sugar must be sure that the sugar under normal conditions of use is of high quality and is not harmful to the health of the product. One reason for the decline in the quality of sugar is bacterial contamination. This is because the sugar industry products are good targets for the development of different groups of microorganisms, e.g., Bacillus subtilis, Clostridium perfringes, Leuconostoc dextranicum, Torula alba, Pseudomonas fluorescens, Sarcina lutea and others. These organisms are affected with beets, and then with sugar beet chips and diffusion juice fall into the processing line of sugar production. Their number in the diffusion juice varies and depends on many facto rs such as the quality of raw materials, the quality of cleaning beet root colonization of transporter-washing and the supply of water to the diffusion process, the temperature of the diffusion and others. In the diffusion unit has the most favorable conditions for the development of micro-organisms. Some of them, especially resistant bacteria and thermophilic bacteria or their spores, forming a capsule which protects against external influences occur in the final product sugar. When injected into the fresh crop of product (juice, syrup, they begin to multiply rapidly, causing difficulties in the process. The higher seeding beet microorganisms, the more they decompose and emit sucrose metabolism byproducts. To reduce the negative impact of microbiological and reduce losses from decomposition of sucrose conducted research on the possibility of using chlorine-containing substances in the sugar industry. It was established experimentally that the investigated chlorinated drug has bacteriostatic action and can be recommended for use in sugar beet production.

  14. A novel solid dosage form of rifampicin and isoniazid with improved functionality.

    Gohel, Mukesh C; Sarvaiya, Krishnakant G

    2007-08-24

    The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

  15. QR encoded smart oral dosage forms by inkjet printing.

    Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

    2018-01-30

    The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Prevalence and trends of cellulosics in pharmaceutical dosage forms.

    Mastropietro, David J; Omidian, Hossein

    2013-02-01

    Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

  17. Stability of pharmaceutical salts in solid oral dosage forms.

    Nie, Haichen; Byrn, Stephen R; Zhou, Qi Tony

    2017-08-01

    Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid-state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them to avoid and solve the instability issues of pharmaceutical salts in the product design.

  18. Non-Conventional Applications of Computerized Tomography: Analysis of Solid Dosage Forms Produced by Pharmaceutical Industry

    Martins de Oliveira, Jose Jr.; Germano Martins, Antonio Cesar

    2010-01-01

    X-ray computed tomography (CT) refers to the cross-sectional imaging of an object measuring the transmitted radiation at different directions. In this work, we describe a non-conventional application of computerized tomography: visualization and improvements in the understanding of some internal structural features of solid dosage forms. A micro-CT X-ray scanner, with a minimum resolution of 30 μm was used to characterize some pharmaceutical tablets, granules, controlled-release osmotic tablet and liquid-filled soft-gelatin capsules. The analysis presented in this work are essentially qualitative, but quantitative parameters, such as porosity, density distribution, tablets dimensions, etc. could also be obtained using the related CT techniques.

  19. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

  20. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R.

    1992-01-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)

  1. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  2. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R. (Pharmaceutical Profiles Ltd., Nottingham (United Kingdom))

    1992-11-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.).

  3. ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

    C. K. Rameesa

    2015-03-01

    Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

  4. ANTITUBERCULOSIS DRUG DOSAGE FORMS: RANGE, KEY BENEFITS AND PROSPECTS OF TECHNOLOGICAL IMPROVEMENT

    M. E. Kim

    2016-01-01

    Full Text Available Interest to research in the development of new formulations of antituberculosis drugs due to the high incidence of tuberculosis in the Republic of Kazakhstan and the Russian Federation nowadays, including with acquired drug resistance. The reason for the development of acquired drug resistance is to interrupt the treatment of patients is the high toxicity of antituberculosis drugs. The improving the efficiency of antituberculosis therapy remains one of the most pressing.The aim this study was to review the dosage forms of antituberculosis drugs currently used and the ways to improve them.Methods. The study was conducted on the basis of scientific analysis (eLibrary database, PubMed, Cyberleninca, patent (kzpatents, reference (Klifar, Drugs register and technical literature.Results. It was revealed that the antituberculosis drugs are available in the form of tablets, capsules, granules for oral use and injection solutions. The advantages and disadvantages of oral dosage forms of antituberculosis drugs: tablets, capsules, granules, syrups, suspensions are described. The importance of the development and implementation in practice of pediatric formulations of antituberculosis drugs is mentioned. The state of current research inhaled formulations for the treatment of tuberculosis is described. The prospects of directional inhalation exposure by immobilization of antituberculosis drugs in liposomes, niosomes, nanocapsules, micelles, micro- and nanoparticles are mentioned. The prospect of the rectal formulations use is described. The increase in interest in the molecular encapsulation of medicinal substances with cyclodextrins in connection with the possibility of increasing the bioavailability of active ingredients, reduce the harmful effects on the gastrointestinal tract, extension, elimination of interaction of incompatible components in combination preparations, the protection of unstable substances is

  5. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie

    2016-01-01

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading...

  6. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  7. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  8. 21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

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

    Al-Gousous, Jozef; Langguth, Peter

    2015-09-01

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

  10. Nanofibrous solid dosage form of living bacteria prepared by electrospinning

    I. Wagner

    2014-05-01

    Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.

  11. Comprehensive review on additives of topical dosage forms for drug delivery.

    Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

  12. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

  13. Preactivated thiolated nanoparticles: A novel mucoadhesive dosage form.

    Menzel, Claudia; Bonengel, Sonja; Pereira de Sousa, Irene; Laffleur, Flavia; Prüfert, Felix; Bernkop-Schnürch, Andreas

    2016-01-30

    Within this study a novel form of mucoadhesive nanoparticles (NPs) exhibiting a prolonged residence time on mucosal tissues was developed. In order to achieve this goal a new thiomer was synthesized by the covalent attachment of the amino acid l-cysteine ethyl ester to poly(acrylic acid) (100 kDa). The free thiol groups were in the following preactivated with the aromatic thiol bearing ligand 2-mercaptonicotinic acid (2-MNA) and the amount of coupled l-cysteine ethyl ester as well as the amount of attached 2-MNA was determined. Based on this, preactivated thiomer NPs were prepared by ionic gelation with polyethylenimine (PEI). The resulting NPs were characterized regarding size and zeta potential. Furthermore their mucoadhesive properties were investigated via rheological measurements with porcine intestinal mucus and via determination of the particles' mucosal residence time. Results showed that 1666.74 μmol l-cysteine ethyl ester and 603.07 μmol 2-MNA could be attached per gram polymer. NPs were in a size range of 112.67-252.84 nm exhibiting a zeta potential of -29 mV. Thiolated NPs only led to a 2-fold increase in mucus viscosity whereas preactivated NPs showed a 6-fold higher mucus viscosity than unmodified NPs. The mucosal residence time of thiolated NPs was 1.6-fold prolonged and that of preactivated NPs even 4.4-fold higher compared to unmodified particles. Accordingly, preactivated thiolated NPs providing a prolonged residence time on mucosal membranes could be a promising dosage form for various applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Influence of dosage form on the intravitreal pharmacokinetics of diclofenac.

    Durairaj, Chandrasekar; Kim, Stephen J; Edelhauser, Henry F; Shah, Jaymin C; Kompella, Uday B

    2009-10-01

    To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Diclofenac acid with an approximate 5-mum particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. By choosing a less soluble form of a drug such as diclofenac acid, vitreous

  15. Mathematical modeling of drug release from lipid dosage forms.

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

    Goole, J; Vanderbist, F; Amighi, K

    2007-04-04

    This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

  18. A step toward development of printable dosage forms for poorly soluble drugs

    Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

    2013-01-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

  19. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

  20. Model-based analysis of a twin-screw wet granulation system for continuous solid dosage manufacturing

    Kumar, Ashish; Vercruysse, Jurgen; Mortier, Severine T. F. C.

    2016-01-01

    Implementation of twin-screw granulation in a continuous from-powder-to-tablet manufacturing line requires process knowledge development. This is often pursued by application of mechanistic models incorporating the underlying mechanisms. In this study, granulation mechanisms considered to be domi......Implementation of twin-screw granulation in a continuous from-powder-to-tablet manufacturing line requires process knowledge development. This is often pursued by application of mechanistic models incorporating the underlying mechanisms. In this study, granulation mechanisms considered...... to be dominant in the kneading element regions of the granulator i.e., aggregation and breakage, were included in a one-dimensional population balance model. The model was calibrated using the experimentally determined inflow granule size distribution, and the mean residence time was used as additional input...

  1. 21 CFR 520.905b - Fenbendazole granules.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole granules. 520.905b Section 520.905b... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905b Fenbendazole granules. (a) Specifications. Each gram of granules contains 222 milligrams (mg) fenbendazole. (b) Sponsor. See...

  2. How to stabilize cilazapril-containing solid dosage forms? The optimization of a final drug formulation

    Katarzyna Regulska

    2017-03-01

    . It was suggested that in the manufacture of cilazapril-containing solid dosage forms the procedure of wet granulation should be avoided while hygroscopic excipients should be substituted by their non-hygroscopic counterparts.

  3. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

    Baranowski, Przemysław; Karolewicz, Bożena; Gajda, Maciej; Pluta, Janusz

    2014-01-01

    This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to...

  4. 76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    2011-12-29

    .... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

  5. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D I R K W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-01-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To clarify the Biopharmaceutics Classification System (BCS) classification, experimental solubility and

  6. Miniaturized approach for excipient selection during the development of oral solid dosage form

    Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus

    2014-01-01

    The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

  7. Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

    Przemysław Baranowski

    2014-01-01

    Full Text Available This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient’s compliance.

  8. PREPARATION AND CHARACTERIZATION OF CO-PROCESSED EXCIPIENT-PREGELATINIZED CASSAVA STARCH PROPIONATE AS A MATRIX IN THE GASTRORETENTIVE DOSAGE FORM

    Junaedi

    2011-11-01

    Full Text Available The gastroretentive dosage form is designed to prolong the gastric residence time of the drug delivery system whichalso results in the development of an appropriate excipient. The purpose of this study is to develop and characterize coprocessedexcipient made from carrageenan (kappa-iota = 1:1 and pregelatinized cassava starch propionate (PCSP inratios of 1:1, 1:2, and 1:3. PCSP was prepared with propionic anhydride in an aqueous medium. The product was mixedwith carrageenan (kappa-iota = 1:1, as well as characterized physicochemical and functional properties. The coprocessedexcipient was then used as a mucoadhesive granule and floating tablet. The USP Basket was selected toperform the dissolution test of the granules in HCl buffer (pH 1.2 and distilled water for 8 hours each. Mucoadhesiveproperties were evaluated using bioadhesive through a vitro test and wash-off test. As for the floating tablet, the USPPaddle was selected to perform the dissolution test of the tablets in 0.1 N HCl for 10 hours. The floating lag time andfloating time were tested in 0.1 N HCl for 24 hours. The result of these studies indicated that co-processed excipientcarrageenan-PCSP can retard dosage form in gastric and drug controlled release, thus making it a suitable material forthe gastroretentive dosage form.

  9. 21 CFR 520.1468 - Naproxen granules.

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1468 Naproxen granules. (a... musculoskeletal system of the horse. (2)(i) For oral maintenance therapy following initial intravenous dosage...

  10. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  11. Design and monitoring of photostability systems for amlodipine dosage forms.

    Ragno, G; Cione, E; Garofalo, A; Genchi, G; Ioele, G; Risoli, A; Spagnoletta, A

    2003-10-20

    Photostability of amlodipine (AML) has been monitored in several pharmaceutical inclusion systems characterized by plurimolecular aggregation of the drug and excipients with high molecular weight. Several formulations including cyclodextrins, liposomes and microspheres have been prepared and characterized. The photodegradation process has been monitored according to the conditions suggested by the ICH Guideline for photostability testing, by using a light cabinet equipped with a Xenon lamp and monitored by spectrophotometry. The formulations herein tested have been found to be able to considerably increase drug stability, when compared with usual pharmaceutical forms. The residual concentration detected in the inclusion complexes with cyclodextrins and liposomes was 90 and 77%, respectively, while a very good value of 97% was found for microspheres, after a radiant exposure of 11,340 kJm(-2).

  12. Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

    Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

    2011-07-01

    In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

  13. Spectroscopic determination of succinylcholine in dosage forms using eosin Y.

    Ayad, Magda M; Belal, Fathalla; Hosney, Mervet M; Abo El Abass, Samah; Elsayed, Nora

    2018-03-01

    Two simple and sensitive analytical assay methods using spectrophotometry and spectrofluorimetry techniques were developed for the estimation of succinylcholine chloride (SUC) in pharmaceutical preparations. The suggested methods are based on the formation of an ion pair complex formed between the drug and eosin Y spectrophotometrically (Method I), or the suppressive effect of succinylcholine on the native fluorescence property of eosin Y (Method II). The spectrophotometric method (Method I) involves measuring the absorbance of the complex between succinylcholine and eosin Y at 550 nm in Britton Robinson buffer of pH 3. However, the spectrofluorimetric method (Method II) involves measuring the quenching effect of the studied drug on the native fluorescence property of eosin Y at the same pH at 550 nm after excitation at 480 nm. The absorbance versus concentration of the drug is rectilinear over the range of 0.5 to 15 μg/ml. The formation constant was 3.5 × 10 4 and the Gibb's free energy change was -2.5 × 10 4  J/mol. In Method II, the relative fluorescence intensity was directly proportional to SUC concentration over the range of 0.05 to 1 μg/ml. The proposed methods allowed a successful application to the estimation of succinylcholine ampoules. An explanation of the reaction pathway was postulated. Copyright © 2017 John Wiley & Sons, Ltd.

  14. HPLC FOR CONTROL STABILITY OF QUERCETIN INJECTABLE DOSAGE FORM

    Martynov AV

    2016-12-01

    Full Text Available Introduction. Quercetin is a flavone derivatives which known like a substances with vitamin activity, high antioxidant, antimutagenic and anticarcinogenic activity and many other types of biological activity. Wide usage of quercetin prevents their polyphenolic nature structure which does not allow a high bioavailability of pure quercetin when administered orally. This is associated with a wide spectrum variety of chemical reactions for the phenolic groups: from interaction with amino acid residues in proteins to reactions with amine heterocyclic alkaloids and polysaccharides. In our days Corvitin – one from the number of quercetin based drugs with sufficiently low levels all types toxicity, allergenic and has no irritating action on intravenous administration. In the same time quercetin cannot be used in full measure because of the limited number of publications with analysis methods, especially HPLC. Determining the stability over time of concentrate quercetin solution, as well as determining the stability of the concentrate to the original autoclave sterilization conditions is a promising direction in creating new drugs. Materials and methods The objective was to research quercetin soluble formulation samples in different conditions: 1 fresh dilute concentrate (0.9% sodium chloride; 2 the original dilute concentrate, which was stored at room temperature for 14 days in light and 3 similar to the first sample dilute concentrate, which went before breeding in autoclaving at 120 0 C for 20 minutes. The objects used in the studies were industrial drug-substance quercetin (Sinkea manufactured (China, the original pharmaceutical composition as the soluble form of quercetin for injection and aerosol applications, glycerol (Sigma, Polysorbat 80 (Merk, ethanol 96 %. For the HPLC – analysis, chromatograph "Milichrom A-02" (SiChrom, Knauer (Econova, Novosibirsk, Russia was used. Results and discussion Quercetin was identified using information on its

  15. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

    Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

    2013-04-10

    A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CVpharmaceutical dosage form.

  18. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  19. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  20. Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

    Evert Fuenmayor

    2018-04-01

    Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

  1. 75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    2010-05-12

    .... FDA-2010-N-0002] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... are treated with a topical solution of ivermectin. DATES: This rule is effective May 12, 2010. FOR... ANADA 200-340 for PRIVERMECTIN (ivermectin), a topical solution used on cattle to control infestations...

  2. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. 76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

    2011-04-22

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

  4. 78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

    2013-05-22

    ...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

  5. Rheology as a tool for evaluation of melt processability of innovative dosage forms

    Aho, Johanna Maaria; Boetker, Johan P; Baldursdottir, Stefania

    2015-01-01

    ) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API...

  6. Study of hydrogels based on polyacrilamide as new controlled release dosage forms produced by frontal polymerization

    Sechi, Rossana; Gavini, Elisabetta; Mariani, Alberto; Bidali, Simone; Bonferoni, Maria Cristina; Sanna, Vanna Annunziata; Rassu, Giovanna; Pirisino, Gerolamo Antonio; Giunchedi, Paolo

    2006-01-01

    The work purpose was the evaluation of the potential application of the Frontal Polymerization (FP) technique as a new method for the preparation of controlled release dosage forms based on polyacrilamide, in which the drug loading and the polymer preparation occur at the same time.

  7. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    2011-01-20

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

  8. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

    2010-04-23

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

  10. 76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

    2011-03-24

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

  11. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. Hot granules medium pressure forming process of AA7075 conical parts

    Dong, Guojiang; Zhao, Changcai; Peng, Yaxin; Li, Ying

    2015-05-01

    High strength aluminum alloy plate has a low elongation at room temperature, which leads to the forming of its components need a high temperature. Liquid or gas is used as the pressure-transfer medium in the existing flexible mould forming process, the heat resistance of the medium and pressurizing device makes the application of aluminum alloy plate thermoforming restricted. To solve this problem, the existing medium is replaced by the heat-resisting solid granules and the general pressure equipments are applied. Based on the pressure-transfer performance test of the solid granules medium, the feasibility that the assumption of the extended Drucker-Prager linear model can be used in the finite element analysis is proved. The constitutive equation, the yield function and the theoretical forming limit diagram(FLD) of AA7075 sheet are established. Through the finite element numerical simulation of hot granules medium pressure forming(HGMF) process, not only the influence laws of the process parameters, such as forming temperature, the blank-holder gap and the diameter of the slab, on sheet metal forming performance are discussed, but also the broken area of the forming process is analyzed and predicted, which are coincided with the technological test. The conical part whose half cone angle is 15° and relative height H/d 0 is 0.57, is formed in one process at 250°C. The HGMF process solves the problems of loading and seal in the existing flexible mould forming process and provides a novel technology for thermoforming of light alloy plate, such as magnesium alloy, aluminium alloy and titanium alloy.

  14. Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

    Zorica Djurić

    2012-10-01

    Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

  15. A Validated RP-HPLC Method for the Determination of Atazanavir in Pharmaceutical Dosage Form

    K. Srinivasu

    2011-01-01

    Full Text Available A validated RP HPLC method for the estimation of atazanavir in capsule dosage form on YMC ODS 150 × 4.6 mm, 5 μ column using mobile phase composition of ammonium dihydrogen phosphate buffer (pH 2.5 with acetonitrile (55:45 v/v. Flow rate was maintained at 1.5 mL/min with 288 nm UV detection. The retention time obtained for atazanavir was at 4.7 min. The detector response was linear in the concentration range of 30 - 600 μg/mL. This method has been validated and shown to be specific, sensitive, precise, linear, accurate, rugged, robust and fast. Hence, this method can be applied for routine quality control of atazanavir in capsule dosage forms as well as in bulk drug.

  16. Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

    Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J.; Tucci, Joseph

    2018-01-01

    The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases. PMID:29495355

  17. Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

    Qu, Li; Morton, David A V; Zhou, Qi Tony

    2015-01-01

    Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

  18. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

    Chen YC; Ho HO; Chiu CC; Sheu MT

    2013-01-01

    Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioav...

  19. ANALYTICAL STUDY OF CURCUMIN CONTENT IN DIFFERENT DOSAGE FORMS CONTAINING TURMERIC EXTRACT POWDER AND TURMERIC OLEORESIN

    Rane Rajashree; Gangolli Divya; Patil Sushma; Ingawale Kanchan; Kundalwal Sachin

    2013-01-01

    Different dosage forms namely tablets, capsules, creams and syrups were analysed for curcumin content, by the well-known spectrophotometric method. Turmeric extract powder was used as a source of curcumin in capsule and tablet formulations. Turmeric oleoresin was used as a source of curcumin in cream formulation. Additionally, syrup formulations containing turmeric extract powder as well as turmeric oleoresin, separately, were also tested for their curcumin contents. Analytical results for cu...

  20. Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons / Marga le Roux

    Le Roux, Marga

    2004-01-01

    Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and me...

  1. Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

    Schneider, Felix; Hoppe, Melanie; Koziolek, Mirko; Weitschies, Werner

    2018-05-29

    Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

  2. Spectrophotometric simultaneous determination of Rabeprazole Sodium and Itopride Hydrochloride in capsule dosage form

    Sabnis, Shweta S.; Dhavale, Nilesh D.; Jadhav, Vijay. Y.; Gandhi, Santosh V.

    2008-03-01

    A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231 nm (minima) and 260 nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

  3. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    Patrick P. DeLuca

    2010-09-01

    Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  4. Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

    Hancock, Bruno C; Ketterhagen, William R

    2011-10-14

    Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

  6. Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers.

    Petereit, H U; Weisbrod, W

    1999-01-01

    General considerations concerning the stability of coated dosage forms are discussed, in order to avoid predictable interactions which may cause long-term stability problems. As polymers themselves maintain a high chemical stability and a low reactivity, instability phenomena mainly have to be explained by interactions of low molecular weight substances or physical changes. Possible interactions of functional groups can be predicted easily and insulating subcoates are proper countermeasures. Impurities, remaining in the polymeric material from the manufacturing process, may accelerate the hydrolysis of sensitive drugs. Instabilities of coated dosage forms are mainly based on physical interactions, caused by improper formulations of coating suspensions (i.e. plasticizers or pigments) or the film coating process. Residual moisture or solvents, probably enclosed in the core and migrating over time, may increase the permeability of coatings, due to plasticizing effects. The functionality of coatings from aqueous dispersions is linked to coalescence of latex particles. Thus any incomplete film formation, caused by too high or too low coating temperatures, may result in high permeable coatings. During storage, preferably under stress conditions this process will continue and thus change the release profile. Therefore bed temperatures of 10-20 degrees C above MFT must ensure the formation of homogeneous polymer layers during the coating process. Stability test procedures and packaging materials also need to be adapted to the physicochemical properties of the dosage form, in order to get meaningful results in stability tests.

  7. Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

    Blaesi, Aron H; Saka, Nannaji

    2017-11-01

    In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

  8. Development and Validation of a HPLC Method for the Determination of Lacidipine in Pure Form and in Pharmaceutical Dosage Form

    Vinodh, M.; Vinayak, M.; Rahul, K.; Pankaj, P.

    2012-01-01

    A simple and reliable high-performance liquid chromatography (HPLC) method was developed and validated for Lacidipine in pure form and pharmaceutical dosage form. The method was developed on X bridge C-18 column (150 mm x 4.6 mm, 5 μm) with a mobile phase gradient system of ammonium acetate and acetonitrile. The effluent was monitored by PDA detector at 240 nm. Calibration curve was linear over the concentration range of 50-250 μg/ml. For Intra-day and inter-day precision % RSD values were found to be 0.83 % and 0.41 % respectively. Recovery of Lacidipine was found to be in the range of 99.78-101.76 %. The limits of detection (LOD) and quantification (LOQ) were 1.0 and 7.3 μg/ml respectively. The developed RP-HPLC method was successfully applied for the quantitative determination of lacidipine in pharmaceutical dosage. (author)

  9. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

    Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

    2016-04-01

    Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

  10. Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

    Ahn, H J; Kim, K M; Kim, C K

    1998-07-01

    To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

  11. Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

    Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

    1998-03-01

    The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

  12. Stability Indicating LC-Method for Estimation of Paracetamol and Lornoxicam in Combined Dosage Form

    Shah, Dimal A.; Patel, Neel J.; Baldania, Sunil L.; Chhalotiya, Usman K.; Bhatt, Kashyap K.

    2011-01-01

    A simple, specific and stability indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of paracetamol and lornoxicam in tablet dosage form. A Brownlee C-18, 5 μm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen phosphate:methanol (40:60, v/v) was used. The flow rate was 1.0 ml/min and effluents were monitored at 266 nm. The retention times of paracetamol and lornoxicam ...

  13. Stability-indicating HPLC determination of pramipexole dihydrochloride in bulk drug and pharmaceutical dosage form

    Panditrao, Vedavati M; Sarkate, Aniket P; Sangshetti, Jaiprakash N; Wakte, Pravin S; Shinde, Devanand B

    2011-01-01

    A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for quantitative determination of pramipexole dihydrochloride in bulk drugs and in pharmaceutical dosage form in the presence of degradation products. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using an Ace5-C18 (250×4.6 mm, 5 µm) advance chromatography column, and 10 mmol L-1 ammonium acetate and acetonitrile (75:25 v/v)...

  14. Colorimetric determination of a paracetamole in raw material and in pharmaceutical dosage forms

    Usifoh, C.O; Adelusi, S.A.; Adebambo, R.F.

    2002-01-01

    A rapid, accurate and simple method is proposed for the determination of p-acetaminophen (paracetamole) in raw material, tablets and syrups. The method is based on measuring the intensity of the yellow color that developed when acute acetaminophen is allowed to react with p-dimethylaminobenzaldehyde in 2M HCl after heating. The color which absorbs in the visible region of gamma 450 nm is stable for several hours and the intensity is directly proportional to the concentration of the drug, that is, Beer lambert law is obeyed. The method can be used to analyse paracetamole in raw material and in pharmaceutical dosage forms. (author)

  15. Analytical Method Development and Validation of Solifenacin in Pharmaceutical Dosage Forms by RP-HPLC

    Shaik, Rihana Parveen; Puttagunta, Srinivasa Babu; Kothapalli Bannoth, Chandrasekar; Challa, Bala Sekhara Reddy

    2014-01-01

    A new, accurate, precise, and robust HPLC method was developed and validated for the determination of solifenacin in tablet dosage form. The chromatographic separation was achieved on an Inertsil ODS 3V C18 (150 mm × 4.6 mm, 5 μm) stationary phase maintained at ambient temperature with a mobile phase combination of monobasic potassium phosphate (pH 3.5) containing 0.1% triethylamine and methanol (gradient mode) at a flow rate of 1.5 mL/min, and the detection was carried out by using UV detect...

  16. HPLC DETERMINATION OF FENBENDAZOLE AND IVERMECTIN SIMULTANEOUSLY IN BULK AND PHARMACEUTICAL DOSAGE FORMS

    Battula Sreenivasa Rao, Mandapati Varaprasad Reddy*, Bhatraju Sreenivasa Rao

    2017-01-01

    In the present study, a simple, precise and accurate high performance liquid chromatography with photodiode array detector was developed for the simultaneous estimation of ivermectin & fenbendazole in bulk and tablet dosage forms. A Zorbax C8 column (250 cm × 4.6 mm × 5 μm) with mobile phase consisting of 0.1 M potassium dihydrogen orthophosphate and methanol (60:40 v/v) having pH 4.5 (adjusted with orthophosphoric acid) was used. The flow rate was 1.2 ml/min and the effluents were detected a...

  17. Dry coating of solid dosage forms: an overview of processes and applications.

    Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

    2017-12-01

    Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

  18. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

    Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

    2017-12-01

    This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  19. Determination of some histamine H1-receptor antagonists in dosage forms.

    Gazy, Azza A; Mahgoub, Hoda; El-Yazbi, F A; El-Sayed, M A; Youssef, Rasha M

    2002-10-15

    Three simple and accurate methods are presented for determination of Cetirizine, Fexofenadine, Loratadine and Acrivastine in pure form and commercial dosage forms. The first method is based on the reaction of the above cited drugs with bromocresol purple dye to form ion-pair complex extractable with chloroform and subsequently measured spectrophotometrically. Secondly, eosin gives with these drugs ion-pair complex, measurable directly without extraction both spectrophotometrically and spectrofluorimetrically. The last method involves the base-catalysed condensation of mixed anhydrides of organic acids (citric acid/acetic anhydride) where as the tertiary amino group in the above-cited drugs acts as the basic catalyst. The product of condensation is measured spectrophotometrically. All the reaction conditions for the proposed methods have been studied. Copyright 2002 Elsevier Science B.V.

  20. Effect of particle size of granules on some mechanical properties of ...

    Solid dosage forms are invariably multiparticulate systems of heterogenous particle size distribution. The purpose of this study was to investigate the effect of particle size distribution of paracetamol granules on some tablet mechanical properties of paracetamol tablets. Granules were formed by wet massing paracetamol ...

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

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

    2016-08-01

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

  2. Development and Statistical Validation of Spectrophotometric Methods for the Estimation of Nabumetone in Tablet Dosage Form

    A. R. Rote

    2010-01-01

    Full Text Available Three new simple, economic spectrophotometric methods were developed and validated for the estimation of nabumetone in bulk and tablet dosage form. First method includes determination of nabumetone at absorption maxima 330 nm, second method applied was area under curve for analysis of nabumetone in the wavelength range of 326-334 nm and third method was First order derivative spectra with scaling factor 4. Beer law obeyed in the concentration range of 10-30 μg/mL for all three methods. The correlation coefficients were found to be 0.9997, 0.9998 and 0.9998 by absorption maxima, area under curve and first order derivative spectra. Results of analysis were validated statistically and by performing recovery studies. The mean percent recoveries were found satisfactory for all three methods. The developed methods were also compared statistically using one way ANOVA. The proposed methods have been successfully applied for the estimation of nabumetone in bulk and pharmaceutical tablet dosage form.

  3. RP-HPLC Method for the Estimation of Nebivolol in Tablet Dosage Form

    M. K. Sahoo

    2009-01-01

    Full Text Available A reverse phase HPLC method is described for the determination of nebivolol in tablet dosage form. Chromatography was carried on a Hypersil ODS C18 column using a mixture of methanol and water (80:20 v/v as the mobile phase at a flow rate of 1.0 mL/min with detection at 282 nm. Chlorzoxazone was used as the internal standard. The retention times were 3.175 min and 4.158 min for nebivolol and chlorzoxazone respectively. The detector response was linear in the concentration of 1-400 μg/mL. The limit of detection and limit of quantification was 0.0779 and 0.2361 μg/mL respectively. The percentage assay of nebivolol was 99.974%. The method was validated by determining its sensitivity, accuracy and precision. The proposed method is simple, fast, accurate and precise and hence can be applied for routine quality control of nebivolol in bulk and tablet dosage form.

  4. Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release

    Sharad S. Darandale

    2012-10-01

    Full Text Available The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release. It consists of a drug loaded polymeric film made up of a bilayer of immediate (IR and controlled release (CR layers folded into a hard gelatin capsule. Gastroretention results from unfolding and swelling of the film and its bioadhesion to the gastric mucosa. Furosemide, a drug with a narrow absorption window, was selected as the model drug. Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol® 971P NF in the CR layer of the bilayer film resulted in optimum drug release, bioadhesion and mechanical properties. The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drug over 1 h and CR for up to 12 h in acidic medium. X-ray diffraction, differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices. The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic windows.

  5. Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

    Içten, Elçin; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

    2015-05-01

    The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. A progressive review of Sandhana kalpana (Biomedical fermentation): An advanced innovative dosage form of Ayurveda

    Chaudhary, Anand; Singh, Neetu; Dalvi, Madhuri; Wele, Asmita

    2011-01-01

    Sandhana kalpana (biomedical fermented formulations) are one of the best dosage forms of Ayurveda in practice since thousands of years. In order to prepare these medicaments, certain sets of conditions are prearranged, which lead to fermentation. Thus, products bequeath with self-generated ethyl alcohol, which potentiate these preparations (Asava–Arishta), pharmaceutically and therapeutically. Commonly, medicinal and commercial components of these formulations are prompting many researchers to contribute in manufacturing, quality control, safety, and efficacy of these formulations. To cope up with this, literature related to Asava–Arishta has been surveyed from the Vedic period to recent publications of Government of India, ie, Ayurvedic Formulary of India, and presented briefly here. In this review paper, we have discussed pioneering facts such as nature and amount of carbohydrate, type of containers, optimum temperature, variety and relevance of initiator of fermentation, manufacturing, regulatory rules, and business aspects of Asava-Arishta. After going through this basic information, any academician or researcher may show a way to further strengthen this dosage form. PMID:22529661

  7. Development of polymer film dosage forms of lidocaine for buccal administration: II. Comparison of preparation methods.

    Okamoto, Hirokazu; Nakamori, Takahiko; Arakawa, Yotaro; Iida, Kotaro; Danjo, Kazumi

    2002-11-01

    In previous studies, we prepared film dosage forms of lidocaine (LC) with hydroxypropylcellulose (HPC) as a film base using the solvent evaporation (SE) method. However, from the viewpoint of environmental issues, a reduction in organic solvent use in pharmaceutical and other industries is required. In this study, we prepared the LC films by direct compression of the physical mixture (DCPM method) and direct compression of the spray dried powder (DCSD method). Magnesium stearate, which was required as a lubricant for direct compression, showed no effect on the LC release rate. The LC release rate (%/h) was independent of the compression pressure, but a higher pressure was preferable to easily remove the film from the punches. An increase in the film weight decreased the LC release rate expressed in %/h, whereas no significant effect of film weight was observed on the LC release rate from unit surface area expressed in mg/h/cm(2). The LC release rate (%/h) was independent of the LC content, suggesting that the LC release rate (mg/h) can be quantitatively controlled by changing the LC content in the formulation. The LC release rate and penetration rate were affected by the preparation method; that is, DCPM method dosage form. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2424-2432, 2002

  8. Consumer Preferences and Perceptions towards the use Colored Oral Solid Dosage Forms in Baghdad

    Inas Rifaat Ibrahim,*, Mohamed Izham M.I & Mahmoud Al-Haddad

    2010-10-01

    Full Text Available Objective: The main aims of this study were to determine consumers’ preferences and perceptions in Baghdad towards the color of Oral Solid Dosage Form.Materials and Methods: A cross sectional study was conducted using a self–administered questionnaire. A convenient sampling method was adopted to approach the consumers visiting the community pharmacies in Baghdad.The data collected was analyzed using SPSS version 16 ®. Anon-parametric statistics i.e [Chi-square, Mann-Whitney and Kruskal-Wallis tests] were used to evaluate the association of demographic variables with respondents perceptions toward physical characteristics of Oral Solid Dosage Form.Results: Colored OSDF was preferred by 76.4% of consumers.Significant differences in this preference were found among genders (P=0.029; age (P<0.001; educational level (P=0.001;and monthly income level (0.007. Further, consumers perceived that color of OSDF is related with the therapeutic activity of medicine. Significant differences in this perception were found to be influenced by gender (P=0.016; age group(P<0.001; and educational level (P<0.001.Conclusion: In a conclusion, color was the most preferred characteristic of OSDF by Baghdadi consumers with the perceptions that color is related to therapeutic activity of medicines. Gender, age, educational level, and monthly income are important factors that are associated with the preferences and perceptions toward colored OSDF.

  9. Spectrophotometric method for simultaneous estimation of atazanavir sulfate and ritonavir in tablet dosage form

    Disha A Patel

    2015-01-01

    Full Text Available Background: Ritonavir (RTV and atazanavir sulfate (ATV are protease inhibitor and RTV mostly used as a booster for increasing the bioavailability of other protease inhibitors like ATV. Aims: Quality assessment of the new dosage form of RTV and ATV i.e., tablets is very essential and hence this work deals with to develop sensitive, simple and precise method for simultaneous estimation of ATV and RTV in tablet dosage form by absorbance correction method. Materials and Methods: The present work was carried out on Shimadzu Ultraviolate(UV-1700 double beam spectrophotometer with 1 cm path length supported by S Shimadzu, model-1700(Japan, UV-Probe software, version 2.31 was used for spectral measurements with 10 mm matched quartz cells. Standard ATV and RTV were supplied by Cipla Pharmaceutical Ltd. Methanol was purchased from Finar Chemicals Pvt. Ltd. Results and Conclusion: The λmax or the absorption maxima for ATV and RTV were found to be 279 and 240 nm, respectively in methanol as solvent. The drugs follow Beer-Lambert′s law in the concentration range 30-90 and 10-30 μg/mL for ATV and RTV, respectively. The percentage recovery was found to be 100-100.33% and 100-101.5% for ATV and RTV, respectively. The method was validated for different parameters as per the International Conference for Harmonization Guidelines.

  10. Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

    Blackshields, Caroline A; Crean, Abina M

    2018-07-01

    There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

  11. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

    Chen YC

    2013-12-01

    Full Text Available Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs of chitosan (CS and hydroxyethyl cellulose (HEC at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.Keywords: gastroretentive dosage form, chitosan, hydrogel, hydroxyethyl cellulose, swelling, alendronate

  12. The Dosage Form of Aragh in Treatment, from the Iranian Traditional Medicine Perspective.

    Adl, Mehdi; Emtiazi, Majid

    2016-05-01

    The Iranian traditional medicine is one of the branches of complementary medicine and it is based on using the dosage forms of plants. One of the most common forms of pharmaceutical plants is Aragh. Due to ease-of-use, distillate is a more acceptable form among the public. In this article, it is attempted to study the usage forms and effects of Aragh according to the valid traditional medicine resources. This article is a review of Iranian traditional medicine textbooks such as Makhzan-ul-dawiah, Gharabadin Kabir, Cannon of Medicine, and other recent texts on medical plants. According to the traditional medicine, the process of getting Aragh is a kind of distillation, which is performed by using Ghar and Alembic (the equipment that are used in distillation). Distillation is the process of extracting and refining the fluid of a plant. Aragh of the plants is much more effective on the body than the plant itself. Traditional medicine regards Aragh as a new kind of drug (medicine) that is rarely mentioned in older texts (except for golab). However, the modern medicine regards it as a dosage form of essence, which is dissolved in water. The more the essence, the better the distillate gets. According to the traditional medicine sources, since the time of Hakim Aghil Khorasani, Aragh was used more and more every day. About 100 kinds of Araghs are mentioned in ancient texts, which are extracted from simple plants. Considering the distillation process and the way it performs, and by knowing that Aragh is a plant's softest and the most influential entity, it seems that it has a huge effect on Arvah and Ghova, the main parts like heart and brain and nervous parts.

  13. Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron.

    Trastullo, Ramona; Abruzzo, Angela; Saladini, Bruno; Gallucci, Maria Caterina; Cerchiara, Teresa; Luppi, Barbara; Bigucci, Federica

    2016-08-01

    In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A Simple RP-HPLC Method for Quantitation of Itopride HCl in Tablet Dosage Form.

    Thiruvengada, Rajan Vs; Mohamed, Saleem Ts; Ramkanth, S; Alagusundaram, M; Ganaprakash, K; Madhusudhana, Chetty C

    2010-10-01

    An isocratic reversed phase high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been developed for the quantification of itopride hydrochloride in tablet dosage form. The quantification was carried out using C(8) column (250 mm × 4.6 mm), 5-μm particle size SS column. The mobile phase comprised of two solvents (Solvent A: buffer 1.4 mL ortho-phosphoric acid adjusted to pH 3.0 with triethyl amine and Solvent B: acetonitrile). The ratio of Solvent A: Solvent B was 75:25 v/v. The flow rate was 1.0 mL (-1)with UV detection at 220 nm. The method has been validated and proved to be robust. The calibration curve was linear in the concentration range of 80-120% with coefficient of correlation 0.9995. The percentage recovery for itopride HCl was 100.01%. The proposed method was validated for its selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of itopride HCl in tablet dosage formulation.

  15. Extremely fast increase in the organic loading rate during the co-digestion of rapeseed oil and sewage sludge in a CSTR--characterization of granules formed due to CaO addition to maintain process stability.

    Kasina, M; Kleyböcker, A; Michalik, M; Würdemann, H

    2015-01-01

    In a co-digestion system running with rapeseed oil and sewage sludge, an extremely fast increase in the organic loading rate was studied to develop a procedure to allow for flexible and demand-driven energy production. The over-acidification of the digestate was successfully prevented by calcium oxide dosage, which resulted in granule formation. Mineralogical analyses revealed that the granules were composed of insoluble salts of long chain fatty acids and calcium and had a porous structure. Long chain fatty acids and calcium formed the outer cover of granules and offered interfaces on the inside thereby enhancing the growth of biofilms. With granule size and age, the pore size increased and indicated degradation of granular interfaces. A stable biogas production up to the organic loading rate of 10.4 kg volatile solids m(-3) d(-1) was achieved although the hydrogen concentration was not favorable for propionic acid degradation. However, at higher organic loading rates, unbalanced granule formation and degradation were observed. Obviously, the adaption time for biofilm growth was too short to maintain the balance, thereby resulting in a low methane yield.

  16. THE EFFECT OF PREPARATION CONDITIONS OF RAPIDLY SOLIDIFIED IRON BASED GRANULES ON PROPERTIES OF COMPOSITE MATERIAL FORMED BY CASTING TECHNOLOGY

    A. S. Kalinichenko

    2017-01-01

    Full Text Available The variety of requirements for friction pairs requires the development of different technologies for the production of tribological materials with reference to the operation modes. Composite materials obtained by the casting technology have been successfully applied for the normalization of the thermomechanical state of the steam turbines. These composites consist of the matrix based on copper alloys reinforced with cast iron granules. Because the structure and properties of cast iron are determined by the conditions of their production studies have been conducted on determination of preparation conditions on grain structure and properties of the synthesized composite material. Using an upgraded unit for production of granules technological regimes were determined providing narrow fractional composition. It has been found that granules formed are characterized with typical microstructure of white cast iron containing perlite and ledeburite. Microhardness of pilot cast iron granules is characterized by high values (from 7450 up to 9450 MPa and depends on the size of the fraction. Composite materials obtained using experimental granules had a microhardness of the reinforcing cast iron granules about 3500 MPa, and a bronze matrix – 1220 MPa, which is higher than the hardness of the composite material obtained by using the annealed DCL-1granules (2250 MPa. Metal base of experimental granules in the composite material has the structure of perlitic ductile iron with inclusions of ferrite not exceeding 10–15% and set around a flocculent graphite. As a result, the increase of physical-mechanical properties of finished products made of composite material is observed. 

  17. Thermal and Isothermal Methods in Development of Sustained Release Dosage Forms of Ketorolac Tromethamine

    Dimple Chopra

    2008-01-01

    Full Text Available Differential scanning calorimetry (DSC is a rapid and convenient and conclusive method of screening drug-polymer blend during preformulation studies as it allows polymer incompatibility to be established instantaneously. Various batches of matrix tablets of ketorolac tromethamine (KTM with a series of compatible polymers were prepared. Batches of tablets which gave desired sustained release profile were subjected to stability testing according to ICH guidelines. The analysis for drug content was done using high performance liquid chromatography (HPLC method. The results revealed that there was no statistically significant change in drug content after storage of matrix tablets at elevated temperature of 40°C and 75% relative humidity. From our study we conclude that with careful selection of different polymers and their combinations, a stable sustained release oral dosage form of ketorolac tromethamine can be achieved.

  18. [Study on dosage form design for improving oral bioavailability of traditional Chinese medicines].

    Xia, Hai-Jian; Zhang, Zhen-Hai; Yao, Dong-Dong; Jia, Xiao-Bin

    2013-09-01

    Both chemical drugs and traditional Chinese medicines have the problem of low bioavailability. However, as traditional Chinese medicines are a multi-component complex, their dosage forms are required to be designed in line with their characteristics, in order to improve the bioavailability of traditional Chinese medicines. Traditional Chinese medicines are mostly prepared into pill, powder, paste, elixir and decoction, but with such drawbacks as high administration dose and poor efficacy. With the process of modernization of traditional Chinese medicines, new-type preparations have be developed and made outstanding achievements. However, they fail to make an organic integration between traditional Chinese medicine theories and modern preparation theories. Characteristics of traditional Chinese medicines are required to be taken into account during the development of traditional Chinese medicines. In the article, multi-component preparation technology was adopted to establish a multi-component drug release system of traditional Chinese medicines on the basis of multiple components of traditional Chinese medicines.

  19. PAT: From Western solid dosage forms to Chinese materia medica preparations using NIR-CI.

    Zhou, Luwei; Xu, Manfei; Wu, Zhisheng; Shi, Xinyuan; Qiao, Yanjiang

    2016-01-01

    Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Simultaneous UV Spectrophotometric Determination of Cetrizine and Dextromethorphan in Tablet Dosage Form

    R. Vijayalakshmi

    2010-01-01

    Full Text Available Two accurate, precise, sensitve and economical procedures for simultaneous estimation of cetrizine and dextromethorphan in tablet dosage forms have been developed. First method employs formation and solving of simultaneous equations using 230 nm and 280 nm as two analytical wavelengths for both drugs in methanol. The second method is Q-analysis based on measurement of absorptivity at 224 nm (as isobestic point and 280 nm (λmax of CTZ. Cetrizine and dextromethorphan at their respective λmax 280 nm and 230 nm and at 224 nm (isobestic point shows linearity in a concentration range of 10-30 mcg/mL for both the drugs. The recovery studies confirmed accuracy of the proposed methods and low values of standard deviation confirmed precision of the methods. The methods were validated as per ICH guidelines.

  1. A Rapid Determination of Cinnarizine in Bulk and Pharmaceutical Dosage Form by LC

    A. A. Heda

    2010-01-01

    Full Text Available A simple, selective, rapid and precise reverse phase high pressure liquid chromatographic method has been developed for the estimation of cinnarizine from pharmaceutical formulation. The method was developed using MICRA-NPS C18 (length×OD×ID =33×8.0×6.0 mm, 1.5 μm column with a mobile phase consisting of acetonitrile, triethylamine buffer (adjusted to pH 4.5 with 10% w/v potassium hydroxide and tetrahydrofuran in the ratio 30:66:4 respectively, at a flow rate of 0.5 mL/min. Wavelength was fixed at 253 nm. The developed method was validated for linearity, accuracy, precision, limit of detection and limit of quantitation. The proposed method can be used for the routine estimation of cinnarizine in pharmaceutical dosage form.

  2. Development and Validation of UV Spectrophotometric Method For Estimation of Dolutegravir Sodium in Tablet Dosage Form

    Balasaheb, B.G.

    2015-01-01

    A simple, rapid, precise and accurate spectrophotometric method has been developed for quantitative analysis of Dolutegravir sodium in tablet formulations. The initial stock solution of Dolutegravir sodium was prepared in methanol solvent and subsequent dilution was done in water. The standard solution of Dolutegravir sodium in water showed maximum absorption at wavelength 259.80 nm. The drug obeyed Beer-Lamberts law in the concentration range of 5-40 μg/ mL with coefficient of correlation (R"2) was 0.9992. The method was validated as per the ICH guidelines. The developed method can be adopted in routine analysis of Dolutegravir sodium in bulk or tablet dosage form and it involves relatively low cost solvents and no complex extraction techniques. (author)

  3. Chemometric simultaneous determination of Sofosbuvir and Ledipasvir in pharmaceutical dosage form

    Khalili, Mahsa; Sohrabi, Mahmoud Reza; Mirzabeygi, Vahid; Torabi Ziaratgahi, Nahid

    2018-04-01

    Partial least squares (PLS), different families of continuous wavelet transform (CWT), and first derivative spectrophotometry (DS) techniques were studied for quantification of Sofosbuvir (SFB) and Ledipasvir (LDV) simultaneously without separation step. The components were dissolved in Acetonitrile and the spectral behaviors were evaluated in the range of 200 to 400 nm. The ultraviolet (UV) absorbance of LDV exhibits no interferences between 300 and 400 nm and it was decided to predict the LDV amount through the classic spectrophotometry (CS) method in this spectral region as well. Data matrix of concentrations and calibrated models were developed, and then by applying a validation set the accuracy and precision of each model were studied. Actual concentrations versus predicted concentrations plotted and good correlation coefficients by each method resulted. Pharmaceutical dosage form was quantified by developed methods and the results were compared with the High Performance Liquid Chromatography (HPLC) reference method. Analysis Of Variance (ANOVA) in 95% confidence level showed no significant differences among methods.

  4. Multicomponent chemical imaging of pharmaceutical solid dosage forms with broadband CARS microscopy.

    Hartshorn, Christopher M; Lee, Young Jong; Camp, Charles H; Liu, Zhen; Heddleston, John; Canfield, Nicole; Rhodes, Timothy A; Hight Walker, Angela R; Marsac, Patrick J; Cicerone, Marcus T

    2013-09-03

    We compare a coherent Raman imaging modality, broadband coherent anti-Stokes Raman scattering (BCARS) microscopy, with spontaneous Raman microscopy for quantitative and qualitative assessment of multicomponent pharmaceuticals. Indomethacin was used as a model active pharmaceutical ingredient (API) and was analyzed in a tabulated solid dosage form, embedded within commonly used excipients. In comparison with wide-field spontaneous Raman chemical imaging, BCARS acquired images 10× faster, at higher spatiochemical resolution and with spectra of much higher SNR, eliminating the need for multivariate methods to identify chemical components. The significant increase in spatiochemical resolution allowed identification of an unanticipated API phase that was missed by the spontaneous wide-field method and bulk Raman spectroscopy. We confirmed the presence of the unanticipated API phase using confocal spontaneous Raman, which provided spatiochemical resolution similar to BCARS but at 100× slower acquisition times.

  5. HPLC-DAD stability indicating determination of nizatidine in bulk and capsules dosage form

    Tarek S. Belal

    2013-12-01

    Full Text Available This work describes the stability-indicating determination of the H2-receptor antagonist nizatidine in its bulk and capsules dosage form using high performance liquid chromatography coupled with diode array detector (HPLC-DAD. The developed method involved the use of Thermo Hypersil BDS-C8 (4.6 × 250 mm, 5 μm particle size column and a mobile phase composed of 0.05 M phosphoric acid and acetonitrile (50:50, v/v. The mobile phase was pumped at a flow rate of 1 mL/min. Quantification of nizatidine was based on measuring its peak area at 320 nm. The retention time for nizatidine was about 3.61 min. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curve of nizatidine was linear in the range of 5–50 μg/mL with correlation coefficient >0.9999. The drug was subjected to forced-degradation conditions of acidic and basic hydrolysis, oxidation, dry heat and UV photolysis where it showed considerable degradation in basic and oxidative conditions. The proposed method proved to be specific and stability-indicating by resolution of the drug from its forced-degradation products. The validated HPLC method was applied to the analysis of nizatidine in capsules dosage form where it was quantified with recoveries not less than 98.2%. Assay results were statistically compared to USP 2011 pharmacopeial method where no significant difference was observed between the proposed and reference methods.

  6. Kinetic spectrophotometric method for the determination of perindopril erbumine in pure and commercial dosage forms

    Nafisur Rahman

    2017-02-01

    Full Text Available A kinetic spectrophotometric method has been developed for the determination of perindopril erbumine in pure and commercial dosage forms. The method is based on the reaction of drug with potassium permanganate in alkaline medium at room temperature (30 ± 1 °C. The reaction was followed spectrophotometrically by measuring the increase in absorbance with time at 603 nm and the initial rate, fixed time (at 8.0 min and equilibrium time (at 90.0 min methods were adopted for constructing the calibration graphs. All the calibration graphs are linear in the concentration range of 5.0–50.0 μg/ml. The limits of detection for initial rate, fixed time and equilibrium time methods were 0.752, 0.882 and 1.091 μg/ml, respectively. The activation parameters such as Ea, ΔH‡, ΔS‡ and ΔG‡ were also determined for the reaction and found to be 60.93 kJ/mol, 56.45 kJ/mol, 74.16 J/K mol and −6.53 kJ/mol, respectively. The variables were optimized and the proposed methods are validated as per ICH guidelines. The method has been further applied to the determination of perindopril erbumine in commercial dosage forms. The analytical results of the proposed methods when compared with those of the reference method show no significant difference in accuracy and precision and have acceptable bias.

  7. Optimization and validation of spectrophotometric methods for determination of finasteride in dosage and biological forms

    Amin, Alaa S.; Kassem, Mohammed A.

    2012-01-01

    Aim and Background: Three simple, accurate and sensitive spectrophotometric methods for the determination of finasteride in pure, dosage and biological forms, and in the presence of its oxidative degradates were developed. Materials and Methods: These methods are indirect, involve the addition of excess oxidant potassium permanganate for method A; cerric sulfate [Ce(SO4)2] for methods B; and N-bromosuccinimide (NBS) for method C of known concentration in acid medium to finasteride, and the determination of the unreacted oxidant by measurement of the decrease in absorbance of methylene blue for method A, chromotrope 2R for method B, and amaranth for method C at a suitable maximum wavelength, λmax: 663, 528, and 520 nm, for the three methods, respectively. The reaction conditions for each method were optimized. Results: Regression analysis of the Beer plots showed good correlation in the concentration ranges of 0.12–3.84 μg mL–1 for method A, and 0.12–3.28 μg mL–1 for method B and 0.14 – 3.56 μg mL–1 for method C. The apparent molar absorptivity, Sandell sensitivity, detection and quantification limits were evaluated. The stoichiometric ratio between the finasteride and the oxidant was estimated. The validity of the proposed methods was tested by analyzing dosage forms and biological samples containing finasteride with relative standard deviation ≤ 0.95. Conclusion: The proposed methods could successfully determine the studied drug with varying excess of its oxidative degradation products, with recovery between 99.0 and 101.4, 99.2 and 101.6, and 99.6 and 101.0% for methods A, B, and C, respectively. PMID:23781478

  8. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate.

    Chen, Ying-Chen; Ho, Hsiu-O; Chiu, Chiao-Chi; Sheu, Ming-Thau

    2014-01-01

    In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.

  9. Preparation and Characterization of a Gastric Floating Dosage Form of Capecitabine

    Ehsan Taghizadeh Davoudi

    2013-01-01

    Full Text Available Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT. Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC, carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets’ floating lag time was determined to be 30–200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.

  10. Preparation and characterization of a gastric floating dosage form of capecitabine.

    Taghizadeh Davoudi, Ehsan; Ibrahim Noordin, Mohamed; Kadivar, Ali; Kamalidehghan, Behnam; Farjam, Abdoreza Soleimani; Akbari Javar, Hamid

    2013-01-01

    Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.

  11. In vivo evaluation of dosage forms: application of gamma scintigraphy to non-enteral routes of administration.

    Meseguer, G; Gurny, R; Buri, P

    1994-01-01

    The trend to deliver drugs to defined areas of the body involves sophisticated carriers systems. In addition to the in vitro drug release profile one must be aware of the in vivo behaviour of the dosage form and the drug. Gamma scintigraphy is an elegant way to gain insights of the actual in vivo distribution pattern of dosage forms. This technique relies on the use of radioactive tracers included into the medicament and selected so as to enable an optimum detection by a gamma ray camera. The choice of a convenient label enables the in vivo determination of the targeting of the formulation administered through a large number of routes. The present paper reviews applications of gamma scintigraphy for the evaluation of dosage forms administered by the parenteral, rectal, buccal, nasal, pulmonary, and ophthalmic routes.

  12. [Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant].

    Kokurina, E V; Suslina, Z A; Khromov, G L; Davydo, A B; Metelitsa, V I; Ionova, V G; Tanashian, M M; Demina, E G; Bochkareva, E V; Belolipetskaia, V G; Deev, A D; Kucheriaeva, N G; Zidra, S I; Gorin, N N; Rumiantsev, D O

    1998-01-01

    Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.

  13. Spectrofluorimetric protocol for antidepressant drugs in dosage forms and human plasma through derivatization with dansyl chloride

    Mahmoud A. Omar

    2017-05-01

    Full Text Available A reliable, sensitive and selective spectrofluorimetric method has been developed for the determination of certain antidepressant drugs namely sertraline hydrochloride, fluoxetine hydrochloride, paroxetine hydrochloride, amineptine hydrochloride and bupropion hydrochloride in pure forms, pharmaceutical formulation and human plasma. The method is based on the reaction of investigated drugs with 5-(dimethylamino naphthalene-1-sulfonyl chloride (dansyl chloride in the presence of 0.5 M sodium carbonate to yield highly fluorescent derivatives, measured at 450 nm (excitation at 347 nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The calibration plots were constructed over the range of 0.02–0.14 μg mL−1. The proposed method was successfully applied for analysis of cited drugs in dosage forms. The high sensitivity of the proposed method allows the determination of investigated drugs in spiked and real human plasma. Statistical comparisons of the results with the reference methods show an excellent agreement and indicate no significant difference in accuracy and precision.

  14. Dosage response mortality of Japanese beetle, masked chafer, and June beetle (Coleoptera: Scarabaeidae) adults when exposed to experimental and commercially available granules containing Metarhizium brunneum

    Adult beetles of three different white grub species, Japanese beetle, Popillia japonica, June beetle, Phyllophaga spp., and masked chafer, Cyclocephala spp. were exposed to experimental and commercially available granules containing Metarhizium brunneum (Petch) strain F52, to determine susceptibilit...

  15. Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy.

    Reddy, Jay Poorna; Jones, John W; Wray, Patrick S; Dennis, Andrew B; Brown, Jonathan; Timmins, Peter

    2018-04-25

    Form changes during drug product processing can be a risk to the final product quality in terms of chemical stability and bioavailability. In this study, online Raman spectroscopy was used to monitor the form changes in real time during high shear wet granulation of Compound A, a highly soluble drug present at a high drug load in an extended release formulation. The effect of water content, temperature, wet massing time and drying technique on the degree of drug transformation were examined. A designed set of calibration standards were employed to develop quantitative partial least square regression models to predict the concentration of each drug form during both wet granulation and the drying process. Throughout all our experiments we observed complex changes of the drug form during granulation, manifest as conversions between the initial non-solvated form of Compound A, the hemi-hydrate form and the "apparent" amorphous form (dissolved drug). The online Raman data demonstrate that the non-solvated form converts to an "apparent" amorphous form (dissolved drug) due to drug dissolution with no appearance of the hemi-hydrate form during water addition stage. The extent of conversion of the non-solvated form was governed by the amount of water added and the rate of conversion was accelerated at higher temperatures. Interestingly, in the wet massing zone, the formation of the hemi-hydrate form was observed at a rate equivalent to the rate of depletion of the non-solvated form with no change in the level of the "apparent amorphous" form generated. The level of hemi-hydrate increased with an increase in wet massing time. The drying process had a significant effect on the proportion of each form. During tray drying, changes in drug form continued for hours. In contrast fluid bed drying appeared to lock the final proportions of drug form product attained during granulation, with comparatively small changes observed during drying. In conclusion, it was possible to

  16. Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

    Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

    2012-08-01

    A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

  17. Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate.

    Thambavita, Dhanusha; Galappatthy, Priyadarshani; Mannapperuma, Uthpali; Jayakody, Lal; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Groot, Dirk W; Langguth, Peter; Mehta, Mehul; Parr, Alan; Polli, James E; Shah, Vinod P; Dressman, Jennifer

    2017-10-01

    Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE and bioavailability studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875 mg belong to BCS class I, whereas 1000 mg belongs to BCS class II and doses of more than 1000 mg belong to BCS class IV. Considering all aspects, the biowaiver procedure can be recommended for solid oral products of amoxicillin trihydrate immediate-release preparations containing amoxicillin as the single active pharmaceutical ingredient at dose strengths of 875 mg or less, provided (a) only the excipients listed in this monograph are used, and only in their usual amounts, (b) the biowaiver study is performed according to the World Health Organization-, U.S. Food and Drug Administration-, or European Medicines Agency-recommended method using the innovator as the comparator, and (c) results comply with criteria for "very rapidly dissolving" or "similarly rapidly dissolving." Products containing other excipients and those containing more than 875 mg amoxicillin per unit should be subjected to an in vivo BE study. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  18. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-11-01

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  19. Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol.

    Shyu, W C; Mayol, R F; Pfeffer, M; Pittman, K A; Gammans, R E; Barbhaiya, R H

    1993-07-01

    A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.

  20. Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.

    Suganthi, A; John, Sofiya; Ravi, T K

    2008-01-01

    A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.

  1. Transmission FTIR derivative spectroscopy for estimation of furosemide in raw material and tablet dosage form

    Máximo Gallignani

    2014-10-01

    Full Text Available A Fourier transform infrared derivative spectroscopy (FTIR-DS method has been developed for determining furosemide (FUR in pharmaceutical solid dosage form. The method involves the extraction of FUR from tablets with N,N-dimethylformamide by sonication and direct measurement in liquid phase mode using a reduced path length cell. In general, the spectra were measured in transmission mode and the equipment was configured to collect a spectrum at 4 cm−1 resolution and a 13 s collection time (10 scans co-added. The spectra were collected between 1400 cm−1 and 450 cm−1. Derivative spectroscopy was used for data processing and quantitative measurement using the peak area of the second order spectrum of the major spectral band found at 1165 cm−1 (SO2 stretching of FUR with baseline correction. The method fulfilled most validation requirements in the 2 mg/mL and 20 mg/mL range, with a 0.9998 coefficient of determination obtained by simple calibration model, and a general coefficient of variation <2%. The mean recovery for the proposed assay method resulted within the (100±3% over the 80%–120% range of the target concentration. The results agree with a pharmacopoeial method and, therefore, could be considered interchangeable.

  2. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.

    Verbeeck, Roger K; Kanfer, Isadore; Löbenberg, Raimar; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Polli, James E; Parr, Alan; Shah, Vinod P; Mehta, Mehul; Dressman, Jennifer B

    2017-08-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometimes used in production of the finished drug product, not every enalapril maleate-labeled finished product actually contains the maleate salt. Enalapril is not considered to have a narrow therapeutic index. With this background, a biowaiver-based approval procedure for new generic products or after major revisions to existing products is deemed acceptable, provided the in vitro dissolution of both test and reference preparation is very rapid (at least 85% within 15 min at pH 1.2, 4.5, and 6.8). Additionally, the test and reference product must contain the identical active drug ingredient. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  3. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-07-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

  4. Spectrophotometric Quantification of Vilazodone Hydrochloride in Pharmaceutical Dosage Form Using Quality by Design Approach

    Panda, S.S.; Kumar, B.V.V.R.K.; Beg, S.; Behera, S.

    2015-01-01

    The present work deals with development and validation of a novel, robust, precise and accurate spectrophotometric method, for the estimation of vilazodone hydrochloride in tablets using the principle of Quality by Design (QbD). A fractional factorial design (FFD) was employed for initial parameter screening. Further the screened parameters were subjected to central composite design (CCD) for evaluating method robustness and method optimization. Different statistical parameters were evaluated to decide appropriateness of experimental data. Vilazodone shows absorption maximum at 285 nm using methanol. Factor screening slit width and sampling interval were identified as critical method variables, which were further evaluated by a CCD. Good linearity was obtained for vilazodone in the range of 5-60 μg/ mL with R"2 > 0.999. The method was found to be accurate with good average % recovery (more than 100 %). Developed method was validated as per ICH guidelines. Based on QbD development of spectrophotometric method ensured that quality is built into the method. The method was robust and can be applied for determination of the vilazodone in pharmaceutical dosage form. (author)

  5. Validated spectrophotometric methods for simultaneous determination of troxerutin and carbazochrome in dosage form

    Khattab, Fatma I.; Ramadan, Nesrin K.; Hegazy, Maha A.; Al-Ghobashy, Medhat A.; Ghoniem, Nermine S.

    2015-03-01

    Four simple, accurate, sensitive and precise spectrophotometric methods were developed and validated for simultaneous determination of Troxerutin (TXN) and Carbazochrome (CZM) in their bulk powders, laboratory prepared mixtures and pharmaceutical dosage forms. Method A is first derivative spectrophotometry (D1) where TXN and CZM were determined at 294 and 483.5 nm, respectively. Method B is first derivative of ratio spectra (DD1) where the peak amplitude at 248 for TXN and 439 nm for CZM were used for their determination. Method C is ratio subtraction (RS); in which TXN was determined at its λmax (352 nm) in the presence of CZM which was determined by D1 at 483.5 nm. While, method D is mean centering of the ratio spectra (MCR) in which the mean centered values at 300 nm and 340.0 nm were used for the two drugs in a respective order. The two compounds were simultaneously determined in the concentration ranges of 5.00-50.00 μg mL-1 and 0.5-10.0 μg mL-1 for TXN and CZM, respectively. The methods were validated according to the ICH guidelines and the results were statistically compared to the manufacturer's method.

  6. Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form.

    Mendez, Andreas S L; Steppe, Martin; Schapoval, Elfrides E S

    2003-12-04

    A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 degrees C was studied. The results were satisfactory with good stability after 24 h at 4 degrees C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

  7. Microbiological assay for the determination of meropenem in pharmaceutical dosage form.

    Mendez, Andreas S L; Weisheimer, Vanessa; Oppe, Tércio P; Steppe, Martin; Schapoval, Elfrides E S

    2005-04-01

    Meropenem is a highly active carbapenem antibiotic used in the treatment of a wide range of serious infections. The present work reports a microbiological assay, applying the cylinder-plate method, for the determination of meropenem in powder for injection. The validation method yielded good results and included linearity, precision, accuracy and specificity. The assay is based on the inhibitory effect of meropenem upon the strain of Micrococcus luteus ATCC 9341 used as the test microorganism. The results of assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r=0.9999) in the range of 1.5-6.0 microg ml(-1), precise (intra-assay: R.S.D.=0.29; inter-assay: R.S.D.=0.94) and accurate. A preliminary stability study of meropenem was performed to show that the microbiological assay is specific for the determination of meropenem in the presence of its degradation products. The degraded samples were also analysed by the HPLC method. The proposed method allows the quantitation of meropenem in pharmaceutical dosage form and can be used for the drug analysis in routine quality control.

  8. A validated stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms.

    Rao, Dantu Durga; Satyanarayana, N V; Malleswara Reddy, A; Sait, Shakil S; Chakole, Dinesh; Mukkanti, K

    2010-02-05

    A novel stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of purity of desloratadine in presence of its impurities and forced degradation products. The method was developed using Waters Aquity BEH C18 column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 280nm. The run time was 8min within which desloratadine and its five impurities were well separated. Desloratadine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Desloratadine was found to degrade significantly in oxidative and thermal stress conditions and stable in acid, base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, thus proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of desloratadine in pharmaceutical dosage forms.

  9. Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

    Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

    2015-08-01

    Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Bilayered buccal films as child-appropriate dosage form for systemic administration of propranolol.

    Abruzzo, Angela; Nicoletta, Fiore Pasquale; Dalena, Francesco; Cerchiara, Teresa; Luppi, Barbara; Bigucci, Federica

    2017-10-05

    Buccal mucosa has emerged as an attractive site for systemic administration of drug in paediatric patients. This route is simple and non-invasive, even if the saliva wash-out effect and the relative permeability of the mucosa can reduce drug absorption. Mucoadhesive polymers represent a common employed strategy to increase the contact time of the formulation at the application site and to improve drug absorption. Among the different mucoadhesive dosage forms, buccal films are particularly addressed for paediatric population since they are thin, adaptable to the mucosal surface and able to offer an exact and flexible dose. The objective of the present study was to develop bilayered buccal films for the release of propranolol hydrochloride. A primary polymeric layer was prepared by casting and drying of solutions of film-forming polymers, such as polyvinylpyrrolidone (PVP) or polyvinylalcohol (PVA), added with different weight ratios of gelatin (GEL) or chitosan (CH). In order to achieve unidirectional drug delivery towards buccal mucosa, a secondary ethylcellulose layer was applied onto the primary layer. Bilayered films were characterized for their physico-chemical (morphology, thickness, drug content and solid state) and functional (water uptake, mucoadhesion, drug release and permeation) properties. The inclusion of CH into PVP and PVA primary layer provided the best mucoadhesion ability. Films containing CH provided a lower drug release with respect to films containing GEL and increased the amount of permeated drug through buccal mucosa, thanks to its ability of interfering with the lipid organization. The secondary ethylcellulose layer did not interfere with drug permeation, but it could limit drug release in the buccal cavity. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development.

    Qiang, Dongmei; Gunn, Jocelyn A; Schultz, Leon; Li, Z Jane

    2010-12-01

    The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.

  12. Sensitive spectrophotometric determination of metoclopramide hydrochloride in dosage forms and spiked human urine using vanillin

    O. Zenita Devi

    2016-09-01

    Full Text Available A new spectrophotometric method which is simple, sensitive, selective and rapid is described for the determination of metoclopramide hydrochloride (MCP in bulk drug and in dosage forms using vanillin as the chromogenic agent. The method is based on the condensation reaction between primary aromatic amine group present in MCP with aromatic aldehyde, vanillin to produce an intense yellow colored product. The resulting Schiff’s base shows an absorption maximum at 410 nm and the reaction product is stable for more than one day. The reaction was carried out in acetic acid and perchloric acid medium. Beer’s law was obeyed in the concentration range 1.5–15.0 μg ml−1 MCP with a molar absorptivity of 1.89 × 104 l mol−1 cm−1. The limit of detection (LOD and limit of quantification (LOQ were found to be 0.51 and 1.55 μg ml−1, respectively. The method was statistically evaluated by calculating percent relative error (% RE for accuracy and percent relative standard deviation (% RSD for precision, and was applied successfully to the determination of MCP in tablets, in injection and also in spiked human urine. No interference was observed from common additives found in pharmaceutical preparations. The results obtained by the proposed method were validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test. The accuracy and reliability of the method were further ascertained by performing recovery tests via standard-addition technique.

  13. Cathodic adsorptive stripping voltammetric determination of Ribavirin in pharmaceutical dosage form, urine and serum

    Ahmed A. Abdel Gaber

    2017-05-01

    Full Text Available A sensitive, simple and rapid square-wave adsorptive stripping voltammetric method was developed and validated for the determination of Ribavirin in pharmaceutical formulations. The proposed method was based on the electrochemical reduction of Ribavirin at a hanging mercury drop electrode in Britton Robinson buffer at pH 10. A well-defined peak was observed at 880 mV with 30 s of accumulation time and 50 mV of accumulation potential. Under these optimized conditions, the square-wave adsorptive stripping voltammetric peak current showed a linear correlation on drug concentration over the range of 1 × 10−10–2 × 10−7 mol L−1 with a correlation coefficient of 0.9995 for the proposed method. The detection and quantitation limits for this method were 2.02 × 10−10 and 6.80 × 10−10 mol L−1, respectively. The results obtained for intra-day and inter-day precision (as RSD % were between 0.447% and 1.024%. This method was applied successfully for the determination of Ribavirin in its pharmaceutical dosage forms with mean recoveries of 99.68 ± 0.13 with RSD % of 0.81% and 99.20 ± 0.24 with RSD % of 0.49% for two concentrations 5 × 10−9 and 5 × 10−8 mol L−1, respectively for 200 mg capsules. The results obtained from the developed square-wave adsorptive stripping voltammetric method were compared with those obtained by the analytical method reported in the literature.

  14. Development of theophylline sustained release dosage form based on Kollidon SR.

    Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

    2002-01-01

    Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

  15. Development of alternative methods for the determination of raloxifene hydrochloride in tablet dosage form

    Fernanda Rodrigues Salazar

    2015-06-01

    Full Text Available Three methods are proposed for the quantitative determination of raloxifene hydrochloride in pharmaceutical dosage form: ultraviolet method (UV high performance liquid chromatography (HPLC and micellar capillary electrophoresis (MEKC. These methods were developed and validated and showed good linearity, precision and accuracy. Also they demonstrated to be specific and robust. The HPLC and MEKC methods were tested in regards to be stability indicating methods and they showed to have this attribute. The UV method used methanol as solvent and optimal wavelength at 284 nm, obeying Lambert-Beer law in these conditions. The chromatographic conditions for the HPLC method included: NST column C18 (250 x 4.6 mm x 5 µm, mobile phase water:acetonitrile:triethylamine (67:33:0,3 v/v, pH 3.5, flow rate 1.0 mL min-1, injection volume 20.0 µl, UV detection 287 nm and analysis temperature 30 °C. The MEKC method was performed on a fused-silica capillary (40 cm effective length x 50 µm i.d. using as background electrolyte 35.0 mmol L-1 borate buffer and 50.0 mmol L-1 anionic detergent sodium dodecyl sulfate (SDS at pH 8.8. The capillary temperature was 32°C, applied voltage 25 kV, UV detection at 280 nm and injection was perfomed at 45 mBar for 4 s, hydrodimanic mode. In this MEKC method, potassium diclofenac (200.0 µg mL-1 was used as internal standard. All these methods were statistically analyzed and demonstrated to be equivalent for quantitative analysis of RLX in tablets and were successfully applied for the determination of the drug.

  16. Stability of Dosage Forms in the Pharmaceutical Payload Aboard Space Missions

    Du, Brian J.; Daniels, Vernie; Boyd, Jason L.; Crady, Camille; Satterfield, Rick; Younker, Diane R.; Putcha, Lakshmi

    2009-01-01

    Efficacious pharmaceuticals with adequate shelf lives are essential for successful space medical operations. Stability of pharmaceuticals, therefore, is of paramount importance for assuring the health and wellness of astronauts on future space exploration missions. Unique physical and environmental factors of space missions may contribute to the instability of pharmaceuticals, e.g., radiation, humidity and temperature variations. Degradation of pharmaceutical formulations can result in inadequate efficacy and/or untoward toxic effects, which could compromise astronaut safety and health. Methods: Four identical pharmaceutical payload kits containing 31 medications in different dosage forms (liquid, tablet, capsule, ointment and suppository) were transported to the International Space Station aboard the Space Shuttle (STS-121). One of the 4 kits was stored on the Shuttle and the other 3 were stored on the International Space Station (ISS) for return to Earth at 6-month interval aboard a pre-designated Shuttle flight for each kit. The kit stored on the Shuttle was returned to Earth aboard STS-121 and 2 kits from ISS were returned on STS 117 and STS-122. Results: Analysis of standard physical and chemical parameters of degradation was completed for pharmaceuticals returned by STS-121 after14 days, STS - 117 after11 months and STS 122 after 19 months storage aboard ISS. Analysis of all flight samples along with ground-based matching controls was completed and results were compiled. Conclusion: Evaluation of results from the shuttle (1) and ISS increments (2) indicate that the number of formulations degraded in space increased with duration of storage in space and was higher in space compared to their ground-based counterparts. Rate of degradation for some of the formulations tested was faster in space than on Earth. Additionally, some of the formulations included in the medical kits were unstable, more so in space than on the ground. These results indicate that the

  17. 75 FR 20268 - Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor; Propofol

    2010-04-19

    ... 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug, and Cosmetic Act and under... use in dogs and cats--(1) Amount. The drug is administered by intravenous injection as follows: (i) Dogs. For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 mg...

  18. New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

    Rania A. Sayed

    2013-01-01

    Full Text Available Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I, clarithromycin (II, and azithromycin dihydrate (III in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I, (II, and (III, respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beer's law was obeyed. The correlation coefficient ( for the studied drugs was found to be 0.9999. The molar absorptivity (, Sandell’s sensitivity, limit of detection (LOD, and limit of quantification (LOQ were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

  19. Spectrophotometric methods for the simultaneous estimation of ofloxacin and tinidazole in bulk and pharmaceutical dosage form

    Kareti Srinivasa Rao

    2011-01-01

    Full Text Available Aim: This work deals with the simultaneous estimation of Ofloxacin (OFL and Tinidazole (TNZ in in bulk and pharmaceutical dosage form, without prior separation, by three different techniques (Simultaneous equation, Absorbance ratio method and First order derivative method. Materials and Methods: The present work was carried out on Shimadzu electron UV1800 double beam UV-Visible spectrophotometer. The absorption spectra of reference and test solutions were carried out in 1 cm matched quartz cell over the range of 200 - 400 nm. Standard gift sample of OFL and TNZ obtain from Torrent pharmaceuticals Ltd., Baddi, Himachal Pradesh. Combined OFL and TNZ tablets were purchased from local market. Methanol from Merck Ltd and distilled water are used as solvent. Results: The first method is the application of simultaneous equation. Where the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50 μg/ml respectively. The second method is the determination of ratio of absorbance at 278nm, the maximum absorption of TNZ and isobestic wavelength 283 nm, the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50μg/ml respectively. The third method is the first order derivative method, where the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50 μg/ml respectively. The results of the analysis have been validated statistically and by recovery studies, where the percentage recovery was found to be 100.9±0.49 and 97.30±0.20 using the simultaneous equation method, 98±0.45 and 100.4±0.48 using the graphical absorbance ratio method and 99.10±0.40 and 84.70±0.70 using first derivative method, for OFL and TNZ respectively. Conclusions: The proposed procedures are rapid, simple, require no preliminary separation steps and can be used for routine analysis of both drugs in quality control laboratories.

  20. In vitro conditions modify immunoassayability of bovine pituitary prolactin and growth hormone: insights into their secretory granule storage forms

    Lorenson, M.Y.

    1985-01-01

    The amount of immunoassayable intracellular bovine (b) PRL and GH varies depending on treatment conditions. The present studies were designed to characterize the mechanisms involved and to compare immunoassayability of both hormones under similar conditions. Pituitary homogenate and secretory granule hormones displayed both time- and temperature-dependent increases when incubated at pH 10.5 with reduced glutathione. Changes in immunoassayability seem to reflect conversion from poorly immunoactive tissue hormone oligomers to monomeric hormone. The data indicate that oligomeric bPRL is stabilized primarily by intermolecular disulfide bonds, although it is also susceptible to urea, SDS, and EDTA; granule thiols may also influence the conversion to monomer. The storage form of bGH appears to be stabilized differently. Maneuvers demonstrated in these studies to influence immunoassayability correlate very well with their previously established effects on hormone release and secretion, strengthening the likelihood that a functional link exists between assayability and secretion

  1. Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms.

    Dashevskiy, Andriy; Mohylyuk, Valentyn; Ahmed, Abid Riaz; Kolter, Karl; Guth, Felicitas; Bodmeier, Roland

    2017-09-01

    The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat ® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat ® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.

  2. Laūq: A Sustained-Release Dosage Form for Respiratory Disorders in Traditional Persian Medicine.

    Karegar-Borzi, Hossein; Salehi, Mehdi; Rahimi, Roja

    2016-01-01

    Laūq is a pharmaceutical dosage form that had been mainly used for the treatment of various respiratory disorders in traditional Persian medicine. It is important from 2 aspects: a dosage form with efficient and optimum delivery of drugs to the respiratory tract and biological effects of its ingredients. Natural medicine in laūq has been demonstrated to act in respiratory disorders by their antitussive, antiallergic, anti-inflammatory, antioxidant, spasmolytic, and antibacterial activities. Some of these natural remedies act by most of the mentioned mechanisms such as Cydonia oblonga, Glycyrrhiza glabra, Crocus sativus, Hyssopus officinalis, Foeniculum vulgare, and honey. However, the evidence is limited including Cassia fistula, Papaver somniferum, and Drimia maritima. According to positive pharmacokinetic and pharmacodynamic aspects of laūqs, they may be considered as efficient dosage forms for delivery of drugs to the respiratory tract. For better compatibility of patients, it could be substituted laūqs with newer drug delivery systems like lozenges. © The Author(s) 2015.

  3. Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.

    Arakawa, Yotaro; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2005-09-01

    We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

  4. GC Method Validation for the Analysis of Menthol in Suppository Pharmaceutical Dosage Form

    Murad N. Abualhasan

    2017-01-01

    Full Text Available Menthol is widely used as a fragrance and flavor in the food and cosmetic industries. It is also used in the medical and pharmaceutical fields for its various biological effects. Gas chromatography (GC is considered to be a sensitive method for the analysis of menthol. GC chromatographic separation was developed using capillary column (VF-624 and a flame ionization detector (FID. The method was validated as per ICH guidelines for various parameters such as precision, linearity, accuracy, solution stability, robustness, limit of detection, and quantification. The tested validation parameters were found to be within acceptable limits. The method was successfully applied for the quantification of menthol in suppositories formulations. Quality control departments and official pharmacopeias can use our developed method in the analysis of menthol in pharmaceutical dosage formulation and raw material.

  5. Simultaneous in vivo visualization and localization of solid oral dosage forms in the rat gastrointestinal tract by magnetic resonance imaging (MRI).

    Christmann, V; Rosenberg, J; Seega, J; Lehr, C M

    1997-08-01

    Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have been investigated. Oral contrast agents containing Gd-DTPA were used to depict the lumen of the digestive organs. Solid oral dosage forms were visualized in a rat model by a 1H-MRI double contrast technique (magnetite-labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled minicapsules). Simultaneous visualization of solid oral dosage forms and the GI environment in the rat was possible using MRI. Microtablets could reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI double contrast technique. Fluorine-labelled minicapsules were detectable in the rat stomach by a combination of 1H- and 19F-MRI in vivo. The in vivo 1H-MRI double contrast technique described allows solid oral dosage forms in the rat GI tract to be depicted. Solid dosage forms can easily be labelled by incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI is a promising tool for observing such pharmaceutical dosage forms in humans. Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral dosage forms in more distal parts of the GI tract. Studies correlating MRI examinations with drug plasma levels could provide valuable information for the development of pharmaceutical dosage forms.

  6. Development and validation of a dissolution test with reversed-phase liquid chromatography analysis for rupatadine in tablet dosage forms

    Sérgio Luiz Dalmora

    2010-01-01

    Full Text Available A dissolution test for in vitro evaluation of tablet dosage forms containing 10 mg of rupatadine was developed and validated by RP-LC. A discriminatory dissolution method was established using apparatus paddle at a stirring rate of 50 rpm with 900 mL of deaerated 0.01 M hydrochloric acid. The proposed method was validated yielding acceptable results for the parameters evaluated, and was applied for the quality control analysis of rupatadine tablets, and to evaluate the formulation during an accelerated stability study. Moreover, quantitative analyses were also performed, to compare the applicability of the RP-LC and the LC-MS/MS methods.

  7. New Stability Indicating RP-HPLC Method for the Estimation of Cefpirome Sulphate in Bulk and Pharmaceutical Dosage Forms

    Rao, Kareti Srinivasa; Kumar, Keshar Nargesh; Joydeep, Datta

    2011-01-01

    A simple stability indicating reversed-phase HPLC method was developed and subsequently validated for estimation of Cefpirome sulphate (CPS) present in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a LiChroCART-Lichrosphere100, C18 RP column (250 mm ? 4mm ? 5 ?m) in an isocratic separation mode with mobile phase consisting of methanol and water in the proportion of 50:50 % (v/v), at a flow rate 1ml/min, and the effluent was monitored at 270 nm. The retention time of CPS wa...

  8. Simple and Inexpensive Methods Development for Determination of Venlafaxine Hydrochloride from Its Solid Dosage Forms by Visible Spectrophotometry

    K. Raghubabu

    2012-01-01

    Full Text Available Two simple, sensitive and cost effective visible spectrophotometric methods (M1 and M2 have been developed for the determination of venlafaxine hydrochloride from bulk and tablet dosage forms. The method M1 is based on the formation of green colored coordination complex by the drug with cobalt thiocyanate which is quantitatively extractable into nitro benzene with an absorption maximum of 626.4 nm. The method M2 involves internal salt formation of aconitic anhydride, dehydration product of citric acid [CIA] with acetic anhydride [Ac2O] to form colored chromogen with an absorption maximum of 561.2 nm. The calibration graph is linear over the concentration range of 10-50 µg/mL and 8-24 µg/mL for method M1 and M2 respectively. The proposed methods are applied to commercial available tablets and the results are statistically compared with those obtained by the reference method and validated by recovery studies. The results are found satisfactory and reproducible. These methods are applied successfully for the estimation of the venlafaxine hydrochloride in the presence of other ingredients that are usually present in dosage forms.

  9. Spectrophotometric methods for the determination of benazepril hydrochloride in its single and multi-component dosage forms.

    El-Yazbi, F A; Abdine, H H; Shaalan, R A

    1999-06-01

    Three sensitive and accurate methods are presented for the determination of benazepril in its dosage forms. The first method uses derivative spectrophotometry to resolve the interference due to formulation matrix. The second method depends on the color formed by the reaction of the drug with bromocresol green (BCG). The third one utilizes the reaction of benazepril, after alkaline hydrolysis, with 3-methylbenzothialozone (MBTH) hydrazone where the produced color is measured at 593 nm. The latter method was extended to develop a stability-indicating method for this drug. Moreover, the derivative method was applied for the determination of benazepril in its combination with hydrochlorothiazide. The proposed methods were applied for the analysis of benazepril in the pure form and in tablets. The coefficient of variation was less than 2%.

  10. Development and Validation of RP-HPLC Method for Simultaneous Estimation of Aspirin and Esomeprazole Magnesium in Tablet Dosage Form

    Dipali Patel

    2013-01-01

    Full Text Available A simple, specific, precise, and accurate reversed-phase HPLC method was developed and validated for simultaneous estimation of aspirin and esomeprazole magnesium in tablet dosage forms. The separation was achieved by HyperChrom ODS-BP C18 column (200 mm × 4.6 mm; 5.0 μm using acetonitrile: methanol: 0.05 M phosphate buffer at pH 3 adjusted with orthophosphoric acid (25 : 25 : 50, v/v as eluent, at a flow rate of 1 mL/min. Detection was carried out at wavelength 230 nm. The retention times of aspirin and esomeprazole magnesium were 4.29 min and 6.09 min, respectively. The linearity was established over the concentration ranges of 10–70 μg/mL and 10–30 μg/mL with correlation coefficients (r2 0.9986 and 0.9973 for aspirin and esomeprazole magnesium, respectively. The mean recoveries were found to be in the ranges of 99.80–100.57% and 99.70–100.83% for aspirin and esomeprazole magnesium, respectively. The proposed method has been validated as per ICH guidelines and successfully applied to the estimation of aspirin and esomeprazole magnesium in their combined tablet dosage form.

  11. Overview of PAT process analysers applicable in monitoring of film coating unit operations for manufacturing of solid oral dosage forms.

    Korasa, Klemen; Vrečer, Franc

    2018-01-01

    Over the last two decades, regulatory agencies have demanded better understanding of pharmaceutical products and processes by implementing new technological approaches, such as process analytical technology (PAT). Process analysers present a key PAT tool, which enables effective process monitoring, and thus improved process control of medicinal product manufacturing. Process analysers applicable in pharmaceutical coating unit operations are comprehensibly described in the present article. The review is focused on monitoring of solid oral dosage forms during film coating in two most commonly used coating systems, i.e. pan and fluid bed coaters. Brief theoretical background and critical overview of process analysers used for real-time or near real-time (in-, on-, at- line) monitoring of critical quality attributes of film coated dosage forms are presented. Besides well recognized spectroscopic methods (NIR and Raman spectroscopy), other techniques, which have made a significant breakthrough in recent years, are discussed (terahertz pulsed imaging (TPI), chord length distribution (CLD) analysis, and image analysis). Last part of the review is dedicated to novel techniques with high potential to become valuable PAT tools in the future (optical coherence tomography (OCT), acoustic emission (AE), microwave resonance (MR), and laser induced breakdown spectroscopy (LIBS)). Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Development and Validation of Spectrophotometric Methods for Simultaneous Estimation of Valsartan and Hydrochlorothiazide in Tablet Dosage Form

    Monika L. Jadhav

    2014-01-01

    Full Text Available Two UV-spectrophotometric methods have been developed and validated for simultaneous estimation of valsartan and hydrochlorothiazide in a tablet dosage form. The first method employed solving of simultaneous equations based on the measurement of absorbance at two wavelengths, 249.4 nm and 272.6 nm, λmax for valsartan and hydrochlorothiazide, respectively. The second method was absorbance ratio method, which involves formation of Q-absorbance equation at 258.4 nm (isoabsorptive point and also at 272.6 nm (λmax of hydrochlorothiazide. The methods were found to be linear between the range of 5–30 µg/mL for valsartan and 4–24 μg/mL for hydrochlorothiazide using 0.1 N NaOH as solvent. The mean percentage recovery was found to be 100.20% and 100.19% for the simultaneous equation method and 98.56% and 97.96% for the absorbance ratio method, for valsartan and hydrochlorothiazide, respectively, at three different levels of standard additions. The precision (intraday, interday of methods was found within limits (RSD<2%. It could be concluded from the results obtained in the present investigation that the two methods for simultaneous estimation of valsartan and hydrochlorothiazide in tablet dosage form are simple, rapid, accurate, precise and economical and can be used, successfully, in the quality control of pharmaceutical formulations and other routine laboratory analysis.

  13. Alternative Manufacturing Concepts for Solid Oral Dosage Forms From Drug Nanosuspensions Using Fluid Dispensing and Forced Drying Technology.

    Bonhoeffer, Bastian; Kwade, Arno; Juhnke, Michael

    2018-03-01

    Flexible manufacturing technologies for solid oral dosage forms with a continuous adjustability of the manufactured dose strength are of interest for applications in personalized medicine. This study explored the feasibility of using microvalve technology for the manufacturing of different solid oral dosage form concepts. Hard gelatin capsules filled with excipients, placebo tablets, and polymer films, placed in hard gelatin capsules after drying, were considered as substrates. For each concept, a basic understanding of relevant formulation parameters and their impact on dissolution behavior has been established. Suitable matrix formers, present either on the substrate or directly in the drug nanosuspension, proved to be essential to prevent nanoparticle agglomeration of the drug nanoparticles and to ensure a fast dissolution behavior. Furthermore, convection and radiation drying methods were investigated for the fast drying of drug nanosuspensions dispensed onto polymer films, which were then placed in hard gelatin capsules. Changes in morphology and in drug and matrix former distribution were observed for increasing drying intensity. However, even fast drying times below 1 min could be realized, while maintaining the nanoparticulate drug structure and a good dissolution behavior. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms.

    Abd El-Hay, Soad S; Hashem, Hisham; Gouda, Ayman A

    2016-03-01

    A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L(-1) orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min(-1) flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195-100 μg mL(-1) for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.

  15. Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

    Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

    2014-12-30

    The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-01-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet gr...

  17. Development and Validation of UV Spectrophotometric Method For Determination of Bisoprolol Fumarate in Bulk and Pharmaceutical Dosage Forms

    Shahinaz Mohammed

    2017-10-01

    Full Text Available In this study a simple, accurate and precise UV- spectrophotometric method was developed for the estimation of bisoprolol fumarate (BF in bulk and tablet dosage form. The method was based on measurement of absorbance of BF aqueous solution at 225 nm. Validation was conducted in accordance to ICH guidelines. The calibration curve was linear in the concentration range 5.0-30.0 µg/mL with correlation coefficient not less than 0.996. The limit of detection and limit of quantification were 0.22 μg/ml and 0.66 μg/ml, respectively. Intraday and intermediate precision of the developed method were reflected by the low RSD% values (1.19 and 0.854, respectively. The recovery percentage was 100.6 ± 0.6%, n=3. The proposed method was applied for the assay of BF in three different brands.

  18. Development of polymer film dosage forms of lidocaine for buccal administration. I. Penetration rate and release rate.

    Okamoto, H; Taguchi, H; Iida, K; Danjo, K

    2001-12-13

    We examined the penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration.

  19. Simultaneous Estimation and Validation of Atorvastatin Calcium and Aspirin in Combined Capsule Dosage Form by RP HPLC Method

    B. V. Suma

    2012-01-01

    Full Text Available A new simple, specific, precise and accurate revere phase liquid chromatography method has been developed for estimation of atorvastatin calcium (AST and ASPIRIN (ASP simultaneously in a combined capsule dosage forms. The chromatographic separation was achieved on a 5 – micron C 18 column (250x 4.6mm using a mobile phase consisting of a mixture of Acetonitrile: Ammonium Acetate buffer 0.02M (68:32 pH 4.5. The flow rate was maintained at 0.8 ml/min. The detection of the constituents was done using UV detector at 245 nm for AST and ASP. The retention time of AST and ASP were found be 4.5915 ± 0.0031 min and 3.282 ±0.0024 min respectively. The developed method was validated for accuracy, linearity, precision, limit of detection (LOD and limit of quantification (LOQ and robustness as per the ICH guidelines.

  20. Determination of glibenclamide, metformin hydrochloride and rosiglitazone maleate by reversed phase liquid chromatographic technique in tablet dosage form

    Havele Shweta S.

    2014-01-01

    Full Text Available A simple, precise and accurate high performance liquid chromatography (HPLC method was developed for the simultaneous estimation of metformin hydrochloride, rosiglitazone maleate, glibenclamide present in multicomponent dosage forms. Chromatography was performed on a 25 cm × 4.6 mm i.d., 5-μm particle, C18 column with 78:22 (v/v methanol: 20 mM potassium dihydrogen phosphate buffer as mobile phase at a flow rate of 1.0 ml/min and UV detection at 238 nm for metformin hydrochloride, rosiglitazone maleate, and glibenclamide. The total elution time was shorter than 9 min. This method was found to be precise and reproducible. This proposed method was successfully applied for the analysis of metformin hydrochloride, rosiglitazone maleate, glibenclamide as a bulk drug and in pharmaceutical formulation without any interference from the excipients.

  1. Toward Higher QA: From Parametric Release of Sterile Parenteral Products to PAT for Other Pharmaceutical Dosage Forms.

    Hock, Sia Chong; Constance, Neo Xue Rui; Wah, Chan Lai

    2012-01-01

    Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach for determining the pharmaceutical quality of the finished dosage form. In the case of terminally sterilized parenteral products, the limitations of conventional batch testing have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms, beyond terminally sterilized parenteral products. For parametric release to be possible, manufacturers must be capable of designing quality into the product, monitoring the manufacturing processes, and controlling the quality of intermediates and finished products in real-time. Process analytical technology (PAT) has been thought to be capable of contributing to these prerequisites. It is believed that the appropriate use of PAT tools can eventually lead to the possibility of real-time release of other pharmaceutical dosage forms, by-passing the need for end-product batch testing. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. Last but not least, current regulations governing the use of PAT and the manufacturing challenges associated with PAT implementation are also discussed. Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most

  2. Estimation of Rabeprazole Sodium and Itopride Hydrochloride in Tablet Dosage Form Using Reverse Phase High Performance Liquid Chromatography

    Shaik Harum Rasheed

    2011-01-01

    Full Text Available A reversed phase high performance liquid chromatography (RP-HPLC method was developed, validated and used for the quantitative determination of rabeprazole sodium (RP and itopride hydrochloride (IH, from its tablet dosage form. Chromatographic separation was performed on a Phenomenex C18 column (250 mm × 4.6 mm, 5 μm, with a mobile phase comprising of a mixture of 50 mM ammonium acetate buffer and methanol (20:80v/v, pH 4.5 adjusted with acetic acid, at a flow rate of 1.3 mL/min with detection at 286 nm. Separation was completed in less than 10 min. As per International Conference on Harmonization (ICH guidelines the method was validated for linearity, accuracy, precision, limit of quantitation and limit of detection. Linearity of RP was found to be in the range of 37.5-375 μg/mL and IH was found to be in the range of 5-50 μg/mL. The correlation coefficients were 0.9997 and 0.9995 for RB and IH respectively. The accuracy of the developed method was found to be 98.6-100.7 for RP and 99.42 -100.81 for IH. The experiment shows the developed method is free from interference of excipients. It indicates the developed RP-HPLC method is simple, linear, precise and accurate and it can be conveniently adopted for the routine quality control analysis of the tablet dosage form.

  3. Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine.

    Zaid, Abdel Naser

    2010-10-01

    To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy. Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS. Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient's who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan. The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.

  4. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

    Battu, Sunil Kumar; Repka, Michael A; Maddineni, Sindhuri; Chittiboyina, Amar G; Avery, Mitchell A; Majumdar, Soumyajit

    2010-09-01

    The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.

  5. Stability-Indicating RP-HPLC Method for Determination of Guanfacine Hydrochloride in Bulk Drugs and in Pharmaceutical Dosage Form

    Vinod K. Ahirrao

    2011-04-01

    Full Text Available A novel stability-indicating RP-HPLC method was developed and validated for quantitative determination of guanfacine hydrochloride in bulk drug and in pharmaceutical dosage form. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using Apollo, C18 (250mm x 4.6mm, 5µm column with mobile phase of 50mM Ammonium acetate (volatile buffer and acetonitrile (65:35, v/v. UV detection has been done at wavelength 220 nm. The guanfacine hydrochloride was subjected to the stress conditions of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. The stressed samples were analyzed by the proposed method. The analyte peak shape was excellent. The described method shows excellent linearity over a range of 30 – 450 µg/mL. The correlation coefficient for guanfacine hydrochloride was 0.999. The limit of detection for Guanfacine hydrochloride is 0.011 µg/mL and the limit of quantification is 0.038 µg/mL respectively.Degradation was observed for guanfacine hydrochloride in base, thermal and in 30% H2O2 conditions. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from main peak. The percentage recovery of guanfacine hydrochloride was ranged from (99.2% to 100.5% in pharmaceutical dosage form. The developed method was validated with respect to the linearity, accuracy (recovery, precision, specificity and robustness. The forced degradation studies prove the stability indicating power of the method.

  6. Potential application of surfactant systems in formulation of dosage forms with slightly soluble substances

    Ibrić Svetlana R.

    2012-01-01

    Full Text Available In order to achieve fast release of ibuprofen, slightly soluble model substance (0.52104 mol/l, surfactant systems for oral use with different PEG-40 hydrogenated castor oil (C/diethylene glycol monoethyl ether (T ratios were investigated. Comparison between dissolution profiles for ibuprofen from formulated systems and from two commercial products, film tablets and soft capsules, is presented in this paper. Photon correlation spectroscopy has shown that after high dilution with water, surfactant systems were able to form micellar solutions. The size of micelles varies from 14.8 ± 0,075 nm to 16.2 ± 0,021 nm with increasing C/T ratio from 1:2 to 2:1. Although with increasing content of PEG-40 hydrogenated castor oil larger micelles have formed, lower values of polydispersity index indicated that more homogeneous distribution of micelles size was gained. Conductometric analysis has demonstrated that system composing of C/T ratio 2:1, has shown most pronounced interaction between droplets, which can be seen as high rise of electrical conductivity with increasing water content (% (wwater/wtotal in the sample. No significant difference in percolation threshold between formulations with different C/T ratios was observed. Different surfactant systems were adsorbed on magnesium aluminometasilicate, as adsorbent with high specific active surface (≈300 m2/g, in order to investigate potential influence of adsorbent on ibuprofen dissolution rate. Formulated systems, with or without adsorbent were filled in hard gelatin capsules. The dissolution profiles of ibuprofen from different formulations were obtained in 30 minutes by dissolution apparatus with rotating baskets and compared with dissolution profiles of ibuprofen from commercial products. For formulations without adsorbent faster release of ibuprofen in first minutes of dissolution test, showed formulations with C/T ratio 2:1 and 1:1. Magnesium aluminometasilicate, as adsorbent with high specific

  7. Porosity measurement of solid pharmaceutical dosage forms by gamma-ray transmission

    Martins de Oliveira, Jose; Andreo Filho, Newton; Vinicius Chaud, Marco; Angiolucci, Tatiana; Aranha, Norberto; Germano Martins, Antonio Cesar

    2010-01-01

    The aim of the present work is the determination of porosity in tablets by using the gamma-ray transmission technique. Tablet dissolution depends on some inherent characteristics of the manufacturing process, such as compression force, tablet volume, density and porosity, nature of excipients, preparation methods and its physical-chemical properties. Porosity is a measure of empty spaces in a material and can be determined by various techniques. In this paper, we propose the use of a gamma-ray transmission technique to obtain the porosity of experimental formulation of tablets. The results of porosity were compared with those obtained by using conventional methodology (density and mercury intrusion). The experimental setup for gamma-ray transmission consists of a gamma-ray source of 241 Am (photons of 59.6 keV and an activity of 3.7x10 9 Bq), an NaI(Tl) scintillation detector, collimators and a standard gamma-ray spectrometry electronics. Our results suggest that the gamma-ray transmission technique is a powerful tool for non-destructive porosity quantification of solid pharmaceutical forms and presents smaller errors than those obtained with conventional methodologies.

  8. Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

    Grymonpré, W; Verstraete, G; Vanhoorne, V; Remon, J P; De Beer, T; Vervaet, C

    2018-03-01

    The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high T g - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower T g it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets. Copyright © 2017

  9. Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

    Belal Fathalla

    2011-10-01

    Full Text Available Abstract Background Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form. Results A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL-1 with a lower detection limit of 5.34 × 10-3 μg mL-1 and limit of quantitation of 0.016 μg mL-1. Conclusions The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3 was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.

  10. Stability Indicating Reverse Phase HPLC Method for Estimation of Rifampicin and Piperine in Pharmaceutical Dosage Form.

    Shah, Umang; Patel, Shraddha; Raval, Manan

    2018-01-01

    High performance liquid chromatography is an integral analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect any drug-related impurities that may be introduced during synthesis. A simple, economic, selective, precise, and stability-indicating HPLC method has been developed and validated for analysis of Rifampicin (RIFA) and Piperine (PIPE) in bulk drug and in the formulation. Reversed-phase chromatography was performed on a C18 column with Buffer (Potassium Dihydrogen Orthophosphate) pH 6.5 and Acetonitrile, 30:70), (%, v/v), as mobile phase at a flow rate of 1 mL min-1. The detection was performed at 341 nm and sharp peaks were obtained for RIFA and PIPE at retention time of 3.3 ± 0.01 min and 5.9 ± 0.01 min, respectively. The detection limits were found to be 2.385 ng/ml and 0.107 ng/ml and quantification limits were found to be 7.228ng/ml and 0.325ng/ml for RIFA and PIPE, respectively. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines. Stress study was performed on RIFA and PIPE and it was found that these degraded sufficiently in all applied chemical and physical conditions. Thus, the developed RP-HPLC method was found to be suitable for the determination of both the drugs in bulk as well as stability samples of capsule containing various excipients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

    Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

    2008-11-04

    Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

  12. Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.

    Alhijjaj, Muqdad; Reading, Mike; Belton, Peter; Qi, Sheng

    2015-11-03

    Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.

  13. Development and Validation of a UV Spectrophotometric and a RP-HPLC Methods for Moexipril Hydrochloride in Pure Form and Pharmaceutical Dosage Form

    Mastiholimath, V.S.; Gupte, P.P.; Mannur, V.S.

    2012-01-01

    A simple and reliable UV spectrophotometric and high-performance liquid chromatography (HPLC) methods were developed and validated for Moexipril hydrochloride in pure form and pharmaceutical dosage form. The RP-HPLC method was developed on agilant eclipse C 18 , (150 mm x 4.6 mm, 5 μm) with a mobile phase gradient system of 60 % (methanol:acetonitrile (70:30 % v/v)) : 40 % 20 mM ammonium acetate buffer pH 4.5 (v/v) and UV spectrophotometric method was developed in phosphate buffer pH 6.8. The effluent was monitored by SPD-M20A, prominence PDA detector at 210 nm. Calibration curve was linear over the concentration range of 10-35 μg/ml and 1-9 μg/ml for RP-HPLC and UV with a regression coefficient of 0.999. For RP-HPLC method Inter-day and intra-day precision % RSD values were found to be 1.00078 % and 1.49408 % respectively. For UV method 0.73386 % to 1.44111 % for inter day 0.453864 to 1.15542 intra-day precision. Recovery of Moexipril hydrochloride was found to be in the range of 99.8538 % to 101.5614 % and 100.5297586 % to 100.6431587 % for UV and RP-HPLC respectively. The limits of detection (LOD) and quantification (LOQ) for HPLC were 0.98969 and 2.99907 μg/ml, respectively. The developed RP-HPLC and UV spectrophotometric method was successfully applied for the quantitative determination of Moexipril hydrochloride in pharmaceutical dosage. (author)

  14. Stable aerobic granules in continuous-flow bioreactor with self-forming dynamic membrane.

    Liu, Hongbo; Li, Yajie; Yang, Changzhu; Pu, Wenhong; He, Liu; Bo, Fu

    2012-10-01

    A novel continuous-flow bioreactor with aerobic granular sludge and self-forming dynamic membrane (CGSFDMBR) was developed for efficient wastewater treatment. Under continuous-flow operation, aerobic granular sludge was successfully cultivated and characterized with small particle size of about 0.1-1.0mm, low settling velocity of about 15-25 m/h, loose structure and high water content of about 96-98%. To maintain the stability of aerobic granular sludge, strategies based on the differences of settling velocity and particle-size between granular and flocculent sludge were implemented. Moreover, in CGSFDMBR, membrane fouling was greatly relieved. Dynamic membrane was just cleaned once in more than 45 days' operation. CGSFDMBR presented good performance in treating septic tank wastewater, obtaining average COD, NH(4)(+)-N, TN and TP removal rates of 83.3%, 73.3%, 67.3% and 60%, respectively, which was more efficient than conventional bioreactors since that carbon, nitrogen and phosphorus were simultaneously removed in a single aerobic reactor. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Utility of Charge Transfer and Ion-Pair Complexation for Spectrophotometric Determination of Eletriptan Hydrobromide in Pure and Dosage Forms

    Ayman A. Gouda

    2013-01-01

    Full Text Available Three simple, sensitive, and accurate spectrophotometric methods have been developed for the determination of eletriptan hydrobromide (ELT in pure and dosage forms. The first two methods are based on charge transfer complex formation between ELT and chromogenic reagents quinalizarin (Quinz and alizarin red S (ARS producing charge transfer complexes which showed an absorption maximum at 569 and 533 nm for Quinz and ARS, respectively. The third method is based on the formation of ion-pair complex between ELT with molybdenum(V-thiocyanate inorganic complex in hydrochloric acid medium followed by extraction of the colored ion-pair with dichloromethane and measured at 470 nm. Different variables affecting the reactions were studied and optimized. Beer's law is obeyed in the concentration ranges 2.0–18, 1.0–8.0, and 2.0–32 μg mL−1 for Quinz, ARS, and Mo(V-thiocyanate, respectively. The molar absorptivity, Sandell sensitivity, detection, and quantification limits are also calculated. The correlation coefficients were ≥0.9994 with a relative standard deviation (R.S.D%. of ≤0.925. The proposed methods were successfully applied for simultaneous determination of ELT in tablets with good accuracy and precision and without interferences from common additives, and the validity is assessed by applying the standard addition technique, which is compared with those obtained using the reported method.

  16. Separation and determination of impurities in paracetamol, codeine and pitophenone in the presence of fenpiverinium in combined suppository dosage form.

    Vojta, Jiří; Hanzlík, Pavel; Jedlička, Aleš; Coufal, Pavel

    2015-01-01

    A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated. The separation of paracetamol and its impurities 4-aminophenol, 4-nitrophenol, 4-chloracetanilid; codeine and its impurities methylcodeine, morphine, codeine dimer and 10-hydroxycodeine; pitophenone and its impurities 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid, 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl]benzoic acid 2-(1-piperidinyl)-ethyl ester, methyl ester of 2-(4-hydroxybenzoyl) benzoic acid and fenpiverinium was achieved by using ion-pair reversed phase liquid chromatography with UV detection. Validation parameters such as the precision, accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ) and robustness were verified for all the mentioned impurities of codeine phosphate hemihydrate and 4-aminophenol and 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid as the main degradation products of paracetamol and pitophenone hydrochloride, respectively. The described method was found to be useful for analysis of the stability samples and therefore suitable for routine purity testing of the drug product. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Simultaneous Estimation of Ibuprofen and Phenylephrine Hydrochloride in Bulk and Combined Dosage Form by First Derivative UV Spectrophotometry Method

    Mehul Patel

    2013-01-01

    Full Text Available A simple, precise, rapid, and economic method was developed for the simultaneous determination of Ibuprofen and Phenylephrine HCl in bulk and combined dosage form. This method involves first-order derivative spectroscopy using 248 nm and 237 nm as zero crossing points for Ibuprofen and Phenylephrine HCl, respectively. For spectrophotometric method 0.1 N NaOH was used as a solvent. The linearity was established over the concentration range of 12–72 μg/mL and 1.5–22 μg/mL for Ibuprofen and Phenylephrine HCl with correlation coefficient (r2 of 0.9972 and 0.9981, respectively. The mean % recoveries were found to be in the range of 98.88% and 98.54% for Ibuprofen and Phenylephrine HCl, respectively. Interday and intraday studies showed repeatability of the method. The method was found to be specific and robust. The method was successfully applied to pharmaceutical formulation, with no interference from excipients as indicated by the recovery study. Results of analysis were validated statistically and by recovery studies.

  18. Stability-Indicating Validated HPLC Method for Analysis of Berberine Hydrochloride and Trimethoprim in Pharmaceutical Dosage Form

    Jing-Chun Wang

    2013-01-01

    Full Text Available A stability-indicating HPLC method was developed and validated for the determination of berberine hydrochloride and trimethoprim in pharmaceutical dosage form in the presence of degradation products. The proposed RP-HPLC method utilizes an Agilent TC-C18, 4.6 mm × 250 mm, 5 μm, column using a mobile phase consisting of acetonitrile-50 mM potassium dihydrogen phosphate (30 : 70, v/v, pH adjusted to 3 with orthophosphoric acid at a flow rate of 1.0 mL/min and UV detection at 271 nm. The linearity of berberine hydrochloride and trimethoprim was in the range of 2 to 60 μg/mL (r=0.9996 and 1 to 30 μg/mL (r=0.9995, respectively. Repeatability and intermediate precisions were also determined with percentage relative standard deviation (% RSD less than 2.0%. The limits of detection were found to be 9.8 ng/mL for berberine hydrochloride and 2.5 ng/mL for trimethoprim. The mean recoveries for berberine hydrochloride and trimethoprim were 99.8 and 98.8%, respectively. The stability of the two drugs was determined under different conditions and the proposed method has shown effective separation for their degradation products. And the proposed assays method can thus be considered stability-indicating.

  19. Spectrophotometric and Spectrofluorimetric Methods for the Determination of Dothiepin Hydrochloride in its Pure and Dosage Forms using Eosin

    Walash, M. I.; Belal, F.; El-Enany, N.; Elmansi, H.

    2010-01-01

    Spectrophotometric and spectrofluorimetric methods were developed for the determination of dothiepin hydrochloride (DOP) in different dosage forms. The spectrophotometric method (Method I) is based on formation of a binary complex with eosin at 540 nm in acetate buffer of pH3.7. The absorbance-concentration plot is rectilinear over the range 1–10 μg/mL with LOD of 0.18 μg/mL and LOQ of 0.54 μg/mL. The spectroflurimetric method (Method II) is based on the quantitative quenching effect of Dothiepin on the native fluorescence of eosin at the same pH. The quenching of the fluorescence of eosin was measured at 543 nm after excitation at 304 nm. The fluorescence-concentration plot is rectilinear over the range 0.3–8 μg/ mL with LOD of 0.11 μg/mL and LOQ of 0.34 μg/mL. The proposed methods were successfully applied to the analysis of commercial tablets and capsules containing the drug. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant differences in the accuracy and precision between the two methods respectively. PMID:23675210

  20. Stability indicating RP-LC-PDA method for the quantitative analysis of saxagliptin in pharmaceutical dosage form

    Laís Engroff Scheeren

    2015-06-01

    Full Text Available Saxagliptin is a potent and selective inhibitor of the enzyme dipeptidyl peptidase 4. It is effective in the treatment of type 2 diabetes mellitus because it stimulates the pancreas to produce insulin. In the present study, a liquid chromatography method was developed and validated to quantify the drug in tablets. This method was based on the isocratic elution of saxagliptin, using a mobile phase consisting of 0.1% phosphoric acid at pH 3.0 - methanol (70: 30, v/v at a flow rate of 1 mL.min-1 with UV detection at 225 nm. The chromatographic separation was achieved in 8 minutes on a Waters XBridge C18 column (250 mm x 4.6 mm, 5µm maintained at ambient temperature. The proposed method proved to be specific and robust for the quality control of saxagliptin in pharmaceutical dosage forms, showing good linearity in the range of 15.0 - 100.0 µg.mL-1 (r>0.999, precision (RSD

  1. Simultaneous Estimation of Gemcitabine Hydrochloride and Capecitabine Hydrochloride in Combined Tablet Dosage Form by RP-HPLC Method

    V. Rajesh

    2011-01-01

    Full Text Available A new reverse phase high performance liquid chromatography (RP-HPLC method has been developed for the simultaneous estimation of gemcitabine hydrochloride and capecitabine hydrochloride in combined tablet dosage form. An inertsil ODS-3 C-18 column having dimensions of 250×4.6 mm and particle size of 5 µm, with mobile phase containing a mixture of acetonitrile : water : triethyelamine in the ratio of (70 : 28 : 2v/v was used. The pH of mobile phase was adjusted to 4.0 with ortho-phosphoric acid. The flow rate was 1 mL/min and the column effluents were monitored at 260 nm. The retention time for gemcitabine hydrochloride and capecitabine hydrochloride was found to be 2.76 and 2.3 min respectively. The proposed method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The method was found to be linear in the range of 10-50 µg/mL and 4-24 µg/mL for gemcitabine hydrochloride and capecitabine hydrochloride, with regression coefficient r = 0.999 and r = 0.999, respectively.

  2. Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms.

    Hickey, John M; Sahni, Neha; Toth, Ronald T; Kumru, Ozan S; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B

    2016-10-01

    Liquid chromatographic methods, combined with mass spectrometry, offer exciting and important opportunities to better characterize complex vaccine antigens including recombinant proteins, virus-like particles, inactivated viruses, polysaccharides, and protein-polysaccharide conjugates. The current abilities and limitations of these physicochemical methods to complement traditional in vitro and in vivo vaccine potency assays are explored in this review through the use of illustrative case studies. Various applications of these state-of-the art techniques are illustrated that include the analysis of influenza vaccines (inactivated whole virus and recombinant hemagglutinin), virus-like particle vaccines (human papillomavirus and hepatitis B), and polysaccharide linked to protein carrier vaccines (pneumococcal). Examples of utilizing these analytical methods to characterize vaccine antigens in the presence of adjuvants, which are often included to boost immune responses as part of the final vaccine dosage form, are also presented. Some of the challenges of using chromatographic and LC-MS as physicochemical assays to routinely test complex vaccine antigens are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. New Stability Indicating RP-HPLC Method for the Estimation of Cefpirome Sulphate in Bulk and Pharmaceutical Dosage Forms.

    Rao, Kareti Srinivasa; Kumar, Keshar Nargesh; Joydeep, Datta

    2011-01-01

    A simple stability indicating reversed-phase HPLC method was developed and subsequently validated for estimation of Cefpirome sulphate (CPS) present in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a LiChroCART-Lichrosphere100, C18 RP column (250 mm × 4mm × 5 μm) in an isocratic separation mode with mobile phase consisting of methanol and water in the proportion of 50:50 % (v/v), at a flow rate 1ml/min, and the effluent was monitored at 270 nm. The retention time of CPS was 2.733 min and its formulation was exposed to acidic, alkaline, photolytic, thermal and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. The described method was linear over a range of 0.5-200μg/ml. The percentage recovery was 99.46. F-test and t-test at 95% confidence level were used to check the intermediate precision data obtained under different experimental setups; the calculated value was found to be less than the critical value.

  4. Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

    Berardi, Alberto; Bisharat, Lorina; AlKhatib, Hatim S; Cespi, Marco

    2018-05-07

    Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

  5. Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

    Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

    2012-12-01

    The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

  6. Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

    Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

    2014-07-01

    The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Unveiling multiple solid-state transitions in pharmaceutical solid dosage forms using multi-series hyperspectral imaging and different curve resolution approaches

    Alexandrino, Guilherme L; Amigo Rubio, Jose Manuel; Khorasani, Milad Rouhi

    2017-01-01

    Solid-state transitions at the surface of pharmaceutical solid dosage forms (SDF) were monitored using multi-series hyperspectral imaging (HSI) along with Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC and PARAFAC2). First, the solid-stat...

  8. [Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

    Somogyi, O; Zelko, R

    Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

  9. The knowledge, attitudes and beliefs of patients and their healthcare professionals around oral dosage form modification: A systematic review of the qualitative literature.

    Mc Gillicuddy, Aoife; Kelly, Maria; Crean, Abina M; Sahm, Laura J

    The objective of this systematic review was to synthesize the available qualitative evidence on the knowledge, attitudes and beliefs of adult patients, healthcare professionals and carers about oral dosage form modification. A systematic review and synthesis of qualitative studies was undertaken, utilising the thematic synthesis approach. The following databases were searched from inception to September 2015: PubMed, Medline (EBSCO), EMBASE, CINAHL, PsycINFO, Web of Science, ProQuest Databases, Scopus, Turning Research Into Practice (TRIP), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR). Citation tracking and searching the references lists of included studies was also undertaken. Grey literature was searched using the OpenGrey database, internet searching and personal knowledge. An updated search was undertaken in June 2016. Studies meeting the following criteria were eligible for inclusion; (i) used qualitative data collection and analysis methods; (ii) full-text was available in English; (iii) included adult patients who require oral dosage forms to be modified to meet their needs or; (iv) carers or healthcare professionals of patients who require oral dosage forms to be modified. Two reviewers independently appraised the quality of the included studies using the Critical Appraisal Skills Programme Checklist. A thematic synthesis was conducted and analytical themes were generated. Of 5455 records screened, seven studies were eligible for inclusion; three involved healthcare professionals and the remaining four studies involved patients. Four analytical themes emerged from the thematic synthesis: (i) patient-centred individuality and variability; (ii) communication; (iii) knowledge and uncertainty and; (iv) complexity. The variability of individual patient's requirements, poor communication practices and lack of knowledge about oral dosage form modification, when combined with the complex and multi

  10. Novel potentiometric application for the determination of pantoprazole sodium and itopride hydrochloride in their pure and combined dosage form.

    Ragab, Mona T; Abd El-Rahman, Mohamed K; Ramadan, Nesrin K; El-Ragehy, Nariman A; El-Zeany, Badr A

    2015-06-01

    Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes were developed and investigated. Sensor I was developed using tetraheptylammonium bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer for the determination of the anionic drug pantoprazole sodium sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH), two electrodes (sensors II and III) were developed using potassium tetrakis(4-chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP) as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl-β-cyclodextrin (2-HP βCD) and 4-tert-butylcalix[8]arene (tBC8), were used as ionophores to improve the selectivity of sensors II and III, respectively. The proposed sensors had a linear dynamic range of 1×10(-5) to 1×10(-2) mol L(-1) with Nernstian slopes of -54.83±0.451, 56.90±0.300, and 51.03±1.909 mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also estimated over the pH ranges of 11-13, 3.5-8 and 4-7 for the three sensors, respectively. The proposed sensors displayed useful analytical characteristics for the determination of PAN and ITH in bulk powder, in laboratory prepared mixtures and in combined dosage forms with clear discrimination from several ions, sugars and some common drug excipients. The method was validated according to ICH guidelines. Statistical comparison between the results from the proposed method and the results from the reference methods showed no significant difference regarding accuracy and precision. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Development and validation of spectrophotometric methods for simultaneous estimation of citicoline and piracetam in tablet dosage form

    Akhila Sivadas

    2013-01-01

    Full Text Available Context: Citicoline (CN and piracetam (PM combination in tablet formulation is newly introduced in market. It is necessary to develop suitable quality control methods for rapid and accurate determination of these drugs. Aim: The study aimed to develop the methods for simultaneous determination of CN and PM in combined dosage form. Materials and Methods: The first method was developed by formation and solving simultaneous equations using 280.3 and 264.1 nm as two analytical wavelengths. Second method was absorbance ratio in which wavelengths selected were 256.6 nm as its absorptive point and 280.3 nm as λmax of CN. According to International Conference on Harmonization (ICH norm, the parameters - linearity, precision, and accuracy were studied. The methods were validated statistically and by recovery studies. Results: Both the drugs obeyed Beer-Lambert′s law at the selected wavelengths in concentration range of 5-13 μg/ml for CN and 10-22 μg/ml for PM. The percentage of CN and PM in marketed tablet formulation was found to be 99.006 ± 0.173 and 99.257 ± 0.613, respectively; by simultaneous equation method. For Q-Absorption ratio method the percentage of CN and PM was found to be 99.078 ± 0.158 and 99.708 ± 0.838, respectively. Conclusions: The proposed methods were simple, reproducible, precise and robust. The methods can be successfully applied for routine analysis of tablets.

  12. Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

    El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

    2017-03-01

    A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H 2 SO 4 at λ em  = 364 nm after excitation at λ ex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. The life cycle of platelet granules.

    Sharda, Anish; Flaumenhaft, Robert

    2018-01-01

    Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  14. Development and Validation of RP-HPLC Method for the Simultaneous Determination of Rabeprazole Sodium and Itopride Hydrochloride in Solid Dosage Form

    Rajesh Sharma

    2010-01-01

    Full Text Available A simple, sensitive, precise, accurate, rapid and reproducible reverse phase high performance liquid chromatographic procedure is developed for simultaneous determination of rabeprazole sodium and itopride hydrochloride in solid dosage form. The mobile phase used was a combination of acetonitrile: buffer (35:65 v/v and the pH was adjusted to 7.0 ± 0.1 by addition of triethylamine. The detection of the capsule dosage form was carried out at 266 nm and a flow rate employed was 1 mL/min. Linearity was obtained in the concentration range of 2 to 16 μg/mL of rabeprazole sodium and 5 to 55 μg/mL of itopride hydrochloride with a correlation coefficient of 0.9992 and 0.9996 respectively. The results of the analysis were validated statistically and recovery studies confirmed the accuracy of the proposed method.

  15. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  16. Development and Validation of UV-Visible Spectrophotometric Methods for Simultaneous Estimation of Thiocolchicoside and Dexketoprofen in Bulk and Tablet Dosage Form

    M. T. Harde; S. B. Jadhav; D. L. Dharam; P. D. Chaudhari

    2012-01-01

    Development and validation of two simple, accurate, precise and economical UV Spectrophotometric methods for simultaneous estimation of Thiocolchicoside and Dexketoprofen in bulk and in tablet dosage form. The methods employed were Method-1 Absorbance correction method and Method-2 First order derivative spectroscopic method. In method-1 Absorbance is measured at two wavelengths 370nm at which Dexketoprofen has no absorbance and 255nm at which both the drug have considerable absorbance. In me...

  17. A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method

    Jahan, Md. Sarowar; Islam, Md. Jahirul; Begum, Rehana; Kayesh, Ruhul; Rahman, Asma

    2014-01-01

    A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP) guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and...

  18. A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

    Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

    2017-02-25

    This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same

  19. Development and Validation of a Precise, Single HPLC Method for the Determination of Tolperisone Impurities in API and Pharmaceutical Dosage Forms

    Raju, Thummala Veera Raghava; Seshadri, Raja Kumar; Arutla, Srinivas; Mohan, Tharlapu Satya Sankarsana Jagan; Rao, Ivaturi Mrutyunjaya; Nittala, Someswara Rao

    2012-01-01

    A novel, sensitive, stability-indicating HPLC method has been developed for the quantitative estimation of Tolperisone-related impurities in both bulk drugs and pharmaceutical dosage forms. Effective chromatographic separation was achieved on a C18 stationary phase with a simple mobile phase combination delivered in a simple gradient programme, and quantitation was by ultraviolet detection at 254 nm. The mobile phase consisted of a buffer and acetonitrile delivered at a flow rate 1.0 ml/min. ...

  20. Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

    Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

    2016-05-30

    Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. COMPARISON OF PHYSICAL STABILITY PROPERTIES OF POMEGRANATE SEED OIL NANOEMULSION DOSAGE FORMS WITH LONG-CHAIN TRIGLYCERIDE AND MEDIUM-CHAIN TRIGLYCERIDE AS THE OIL PHASE

    Sri Hartanti Yuliani

    2016-08-01

    Full Text Available Pomegranate seed oil has antioxidant, anti-inflammatory, and chemo preventive activities. Pomegranate seed oil is lipophilic substance suitable to be prepared in emulsion dosage forms. Long-chain triglyceride (LCT and medium-chain triglyceride (MCT are commonly used as oil phase in emulsion dosage forms. This research aimed to compare the use of LCT and MCT in the Nano emulsion formula of pomegranate seed oil dosage forms. Formulation of pomegranate seed oil Nano emulsion was conducted using high energy emulsification. Parameters observed were pH, Nano emulsion type, percent transmittance, viscosity, turbidity, and droplet size before and after 3 cycles of freeze-thaw. The result showed that there was no significant difference between physical properties of pomegranate oil Nano emulsion with LCT as oil phase and pomegranate oil Nano emulsion with MCT as oil phase. Moreover, physical stability of pomegranate oil Nano emulsion with LCT as oil phase was better than pomegranate oil Nano emulsion with MCT as oil phase.

  2. Pasteurization as a tool to control the bio-burden in solid herbal dosage forms: A pilot study of formulating Ashoka tablets with an industrial perspective.

    Pushpalatha, Hulikal Basavarajaiah; Pramod, Kumar; Sundaram, Ramachandran; Shyam, Ramakrishnan

    2014-10-01

    Irradiation and use of preservatives are routine procedures to control bio-burden in solid herbal dosage forms. Use of steam or pasteurization is even though reported in the literature, not many studies are available with respect to its application in reducing the bio-burden in herbal drug formulations. Hence, we undertook a series of studies to explore the suitability of pasteurization as a method to reduce bio-burden during formulation and development of herbal dosage forms, which will pave the way for preparing preservative-free formulations. Optimized Ashoka (Saraca indica) tablets were formulated and developed. The optimized formula was then subjected to pasteurization during formulation, with an aim to keep the microbial count well within the limits of pharmacopoeial standards. Then, three variants of the optimized Ashoka formulation - with preservative, without preservative and formulation without preservative and subjected to pasteurization, were compared by routine in-process parameters and stability studies. The results obtained indicate that Ashoka tablets manufactured by inclusion of the pasteurization technique not only showed the bio-burden to be within the limits of pharmacopoeial standards, but also exhibited the compliance with other parameters, such as stability and quality. The outcome of this pilot study shows that pasteurization can be employed as a distinctive method for reducing bio-burden during the formulation and development of herbal dosage forms, such as tablets.

  3. CFD simulation of flow pattern in a bubble column reactor for forming aerobic granules and its development.

    Fan, Wenwen; Yuan, LinJiang; Li, Yonglin

    2018-06-04

    The flow pattern is considered to play an important role in the formation of aerobic granular sludge in a bubble column reactor; therefore, it is necessary to understand the behavior of the flow in the reactor. A three-dimensional computational fluid dynamics (CFD) simulation for bubble column reactor was established to visualize the flow patterns of two-phase air-liquid flow and three-phase air-liquid-sludge flow under different ratios of height to diameter (H/D ratio) and superficial gas upflow velocities (SGVs). Moreover, a simulation of the three-phase flow pattern at the same SGV and different characteristics of the sludge was performed in this study. The results show that not only SGV but also properties of sludge involve the transformation of flow behaviors and relative velocity between liquid and sludge. For the original activated sludge floc to cultivate aerobic granules, the flow pattern has nothing to do with sludge, but is influenced by SGV, and the vortices is occurred and the relative velocity is increased with an increase in SGV; the two-phase flow can simplify the three-phase flow that predicts the flow pattern development in bubble column reactor (BCR) for aerobic granulation. For the aerobic granules, the liquid flow behavior developed from the symmetrical circular flow to numbers and small-size vortices with an increase in the sludge diameter, the relative velocity is amount up to u r =5.0, it is 29.4 times of original floc sludge.

  4. Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

    Paramakrishnan, N; Jha, S; Kumar, K Jayaram

    2015-05-01

    The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 μm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Development of granules from Phyllanthus niruri spray-dried extract

    Tatiane Pereira de Souza

    2009-12-01

    Full Text Available The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

  6. Significance of excipients to enhance the bioavailability of poorly water-soluble drugs in oral solid dosage forms: A Review

    Vadlamudi, Manoj Kumar; Dhanaraj, Sangeetha

    2017-11-01

    Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Cyclodextrin, Povidone, Copovidone, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Crospovidone, Starch, Dimethylacetamide, Polyethylene glycol, Sodium lauryl sulfate, Polysorbate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

  7. Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms.

    Woltmann, Eva; Meyer, Hans; Weigel, Diana; Pritzke, Heinz; Posch, Tjorben N; Kler, Pablo A; Schürmann, Klaus; Roscher, Jörg; Huhn, Carolin

    2014-10-01

    High production output of solid pharmaceutical formulations requires fast methods to ensure their quality. Likewise, fast analytical procedures are required in forensic sciences, for example at customs, to substantiate an initial suspicion. We here present the design and the optimization of an instrumental setup for rapid and non-invasive characterization of tablets by laser-induced fluorescence spectroscopy (with a UV-laser (λ ex = 266 nm) as excitation source) in reflection geometry. The setup was first validated with regard to repeatability, bleaching phenomena, and sensitivity. The effect on the spectra by the physical and chemical properties of the samples, e.g. their hardness, homogeneity, chemical composition, and granule grain size of the uncompressed material, using a series of tablets, manufactured in accordance with design of experiments, was investigated. Investigation of tablets with regard to homogeneity, especially, is extremely important in pharmaceutical production processes. We demonstrate that multiplicative scatter correction is an appropriate tool for data preprocessing of fluorescence spectra. Tablets with different physical and chemical characteristics can be discriminated well from their fluorescence spectra by subjecting the results to principal component analysis.

  8. Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with β-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

    Souza, Sarah Oliveira Lamas; Cotrim, Monique Alvarenga Pinto; Oréfice, Rodrigo Lambert; Carvalho, Suzana Gonçalves; Dutra, Jessyca Aparecida Paes; de Paula Careta, Francisco; Resende, Juliana Alves; Villanova, Janaina Cecília Oliveira

    2018-05-10

    Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with β-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing β-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.

  9. Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-09-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

  10. Development and Validation of a Stability-Indicating RP-HPLC Method for Rapid Determination of Doxycycline in Pharmaceutical Bulk and Dosage Forms

    Shabnam Pourmoslemi, Soroush Mirfakhraee, Saeid Yaripour, Ali Mohammadi

    2016-01-01

    Background: A rapid stability-indicating RP-HPLC method for analysis of doxycycline in the presence of its degradation products was developed and validated. Methods: Forced degradation studies were carried out on bulk samples and capsule dosage forms of doxycycline using acid, base, H2O2, heat, and UV light as described by ICH for stress conditions to demonstrate the stability-indicating power of the method. Separations were performed on a Perfectsil® Target ODS column (3-5µm, 125 mm×4 mm), u...

  11. Development of a stability-indicating high performance liquid chromatography method for assay of erythromycin ethylsuccinate in powder for oral suspension dosage form

    Fahimeh Kamarei

    2014-12-01

    Full Text Available In this study an effective method was developed to assay erythromycin ethylsuccinate for an oral suspension dosage form. The chromatographic separation was achieved on an X-Terra™ C18 analytical column. A mixture of acetonitrile–ammonium dihydrogen phosphate buffer (0.025 mol L-1 (60:40, V/V (pH 7.0 was used as the mobile phase, effluent flow rate monitored at 1.0 mL min−1, and UV detection at 205 nm. In forced degradation studies, the effects of acid, base, oxidation, UV light and temperature were investigated showing no interference in the peak of drug. The proposed method was validated in terms of specificity, linearity, robustness, precision and accuracy. The method was linear at concentrations ranging from 400 to 600 μg mL−1, precise (intra- and inter-day relative standard deviations <0.65, accurate (mean recovery; 99.5%. The impurities and degradation products of erythromycin ethylsuccinate were selectively determined with good resolution in both the raw material and the final suspension forms. The method could be useful for both routine analytical and quality control assays of erythromycin ethylsuccinate in commercial powder for an oral suspension dosage form and it could be a very powerful tool to investigate the chemical stability of erythromycin ethylsuccinate.

  12. Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.

    Gonzalez, Aroa Garcia; Taraba, Lukáš; Hraníček, Jakub; Kozlík, Petr; Coufal, Pavel

    2017-01-01

    Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Surface modified zeolite-based granulates for the sustained release of diclofenac sodium.

    Serri, Carla; de Gennaro, Bruno; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; De Rosa, Giuseppe; Catalanotti, Lilia; Biondi, Marco; Mayol, Laura

    2017-03-01

    In this study, a granulate for the oral controlled delivery of diclofenac sodium (DS), an anionic sparingly soluble nonsteroidal anti-inflammatory drug, has been realized by wet granulation, using a surface modified natural zeolite (SMNZ) as an excipient. The surface modification of the zeolite has been achieved by means of a cationic surfactant, so as to allow the loading of DS through ionic interaction and bestow a control over the drug release mechanism. The granules possessed a satisfactory dosage uniformity, a flowability suitable for an oral dosage form manufacturing, along with a sustained drug release up to 9h, driven by both ion exchange and transport kinetics. Furthermore, the obtained granulate did not elicit a significant cytotoxicity and could also induce a prolonged anti-inflammatory effect on RAW264.7 cells. Taking also into account that natural zeolites are generally abundant and economic, SMNZ can be considered as an attracting alternative excipient for the production of granules with sustained release features. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Utility of eosin Y as a complexing reagent for the determination of citalopram hydrobromide in commercial dosage forms by fluorescence spectrophotometry.

    Azmi, Syed Najmul Hejaz; Al-Fazari, Ahlam; Al-Badaei, Munira; Al-Mahrazi, Ruqiya

    2015-12-01

    An accurate, selective and sensitive spectrofluorimetric method was developed for the determination of citalopram hydrobromide in commercial dosage forms. The method was based on the formation of a fluorescent ion-pair complex between citalopram hydrobromide and eosin Y in the presence of a disodium hydrogen phosphate/citric acid buffer solution of pH 3.4 that was extractable in dichloromethane. The extracted complex showed fluorescence intensity at λem = 554 nm after excitation at 259 nm. The calibration curve was linear over at concentrations of 2.0-26.0 µg/mL. Under optimized experimental conditions, the proposed method was validated as per ICH guidelines. The effect of common excipients used as additives was tested and the tolerance limit calculated. The limit of detection for the proposed method was 0.121 μg/mL. The proposed method was successfully applied to the determination of citalopram hydrobromide in commercial dosage forms. The results were compared with the reference RP-HPLC method. Copyright © 2015 John Wiley & Sons, Ltd.

  15. A Stability-Indicating HPLC Method for the Determination of Memantine Hydrochloride in Dosage Forms through Derivatization with 1-Fluoro-2,4-dinitrobenzene

    Jalalizadeh, Hassan; Raei, Mahdi; Tafti, Razieh Fallah; Farsam, Hassan; Kebriaeezadeh, Abbas; Souri, Effat

    2014-01-01

    Memantine is chemically a tricyclic amine and is used for Parkinson’s disease and movement disorders. Although several HPLC methods with different derivatization reagents have been developed for the determination of memantine in biological fluids, there are some complications which limit the use of these methods in routine analysis of memantine in in vitro tests. We established a simple, sensitive, precise, and accurate HPLC method for the quantification of memantine in dosage forms. Pre-column derivatization of memantine was performed with 1-fluoro-2,4-dinitrobenzene and the reaction product was separated on a Nova-Pak C18 column. A mixture of acetonitrile and sodium dihydrogenphosphate (pH 2.5; 0.05 M) (70: 30, v/v) was used as the mobile phase. UV detection was performed at 360 nm. Forced degradation studies were performed on a powdered tablet sample of memantine hydro-chloride using acidic (0.1 M hydrochloric acid), basic (0.1 M sodium hydroxide), oxidative (10% hydrogen peroxide), thermal (105°C), photolytic, and humidity conditions. Good linearity (r2=0.999) was obtained over the range of 1–12 μg mL−1 of memantine hydrochloride with acceptable within-day and between-day precision values in the range of 0.05–0.95%. The proposed method was used for the assay determination and dissolution rate study of memantine dosage forms with excellent specificity. PMID:24959398

  16. Development and Validation of a Stability-Indicating RP-HPLC Method for Rapid Determination of Doxycycline in Pharmaceutical Bulk and Dosage Forms

    Shabnam Pourmoslemi, Soroush Mirfakhraee, Saeid Yaripour, Ali Mohammadi

    2016-06-01

    Full Text Available Background: A rapid stability-indicating RP-HPLC method for analysis of doxycycline in the presence of its degradation products was developed and validated. Methods: Forced degradation studies were carried out on bulk samples and capsule dosage forms of doxycycline using acid, base, H2O2, heat, and UV light as described by ICH for stress conditions to demonstrate the stability-indicating power of the method. Separations were performed on a Perfectsil® Target ODS column (3-5µm, 125 mm×4 mm, using a mobile phase consisting of methanol-50 mM ammonium acetate buffer (containing 0.1% v/v trifluoroacetic acid and 0.1% v/v triethylamine, pH 2.5 (50:50 v/v at room temperature. The flow rate was 0.8 mL/min. Results: The method linearity was investigated in the range of 25–500 µg/mL (r > 0.9999. The LOD and LOQ were 5 and 25 µg/mL, respectively. The method selectivity was evaluated by peak purity test using a diode array detector. There was no interference among detection of doxycycline and its stressed degradation products. Total peak purity numbers were in the range of 0.94-0.99, indicating the homogeneity of DOX peaks. Conclusion: These data show the stability-indicating nature of the method for quality control of doxycycline in bulk samples and capsule dosage forms.

  17. Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

    Hammad, Mohamed A; Omar, Mahmoud A; Salman, Baher I

    2017-09-01

    A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml -1 , with quantitation limits 27.1 and 32.2 ng ml -1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Stability-indicating UPLC method for determination of Valsartan and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms.

    Krishnaiah, Ch; Reddy, A Raghupathi; Kumar, Ramesh; Mukkanti, K

    2010-11-02

    A simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of purity of Valsartan drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. The method was developed using Waters Aquity BEH C18 (100 mm x 2.1 mm, 1.7 microm) column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 225 nm, the run time was within 9.5 min, which Valsartan and its seven impurities were well separated. Valsartan was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Valsartan was found to degrade significantly in acid and oxidative stress conditions and stable in base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per international conference on harmonization (ICH) guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of Valsartan in pharmaceutical dosage forms.

  19. A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form

    Runja, Chinnalalaiah; Ravi Kumar, Pigili; Avanapu, Srinivasa Rao

    2016-01-01

    A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 × 4.6 mm, 5 µm) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2–12 µg/mL for EMT, 3–18 µg/mL for TNDF, 1.5–9 µg/mL for ELV and COB, with the coefficient value (R2) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93–100.08 ± 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID:26865655

  20. Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

    Anna Kabanova

    2016-04-01

    Full Text Available Suppression of the cytotoxic T cell (CTL immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs, but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL. Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8. We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.

  1. Mechanism of the formation of hollow spherical granules using a high shear granulator.

    Asada, Takumi; Nishikawa, Mitsunori; Ochiai, Yasushi; Noguchi, Shuji; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-05-30

    Recently, we have developed a novel granulation technology to manufacture hollow spherical granules (HSGs) for controlled-release formulations; however, the mechanism of the granulation is still unclear. The aim of this study is to determine the mechanism of the formation of the HSGs using a high shear granulator. Samples of granulated material were collected at various times during granulation and were investigated using scanning electron microscope and X-ray computed tomography. It was observed that the granulation proceeded by drug layering to the polymer, followed by formation of a hollow in the granule. In addition, it was also found that generation of a crack in the adhered drug layer and air flow into the granules might be involved in forming the hollow in the structure. Observation of the granulation of formulations with different types of drugs and polymers indicated that negative pressure in the granules occurred and the granules caved in when the hollow was formed. The hollow-forming speed and the shell density of the hollow granules depended on the particular drug and polymer. Taken together, the granulation mechanism of HSGs was determined and this information will be valuable for HSGs technology development. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Radiation dosage

    Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

    1986-07-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

  3. Radiation dosage

    Finston, Roland

    1986-01-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

  4. Development and validation of new analytical methods for simultaneous estimation of Drotaverine hydrochloride in combination with Omeprazole in a pharmaceutical dosage form

    Smita Sharma

    2017-02-01

    Full Text Available A rapid and precise method (in accordance with ICH guidelines is developed for the quantitative simultaneous determination of Drotaverine hydrochloride and Omeprazole in a combined pharmaceutical dosage form. Three methods are described for the simultaneous determination of Drotaverine hydrochloride and Omeprazole in a binary mixture. The first method was based on UV-Spectrophotometric determination of two drugs, using Vierordt!s simultaneous equation method. It involves absorbance measurement at 226.8 nm (λmax of Drotaverine hydrochloride and 269.4 nm (λmax of Omeprazole in methanol; linearity was obtained in the range of 5–30 μg ml−1 for both the drugs. The second method was based on HPLC separation of the two drugs using potassium dihydrogen phosphate buffer pH 5.0: Acetonitrile: Triethylamine (60:40:0.5, v/v as a mobile phase. Areas were recorded at 260 nm for both the drugs and retention time was found to be 2.71 min. and 3.87 min for Drotaverine hydrochloride and Omeprazole, respectively at 1.0 mL/min flow rate. The selected chromatographic conditions were found to determine Drotaverine hydrochloride and Omeprazole quantitatively in a combined dosage form without any physical separation. The method has been validated for linearity, accuracy and precision. Linearity was found over the range of 5–30 μg mL−1 for both drugs. The third method was based on HPTLC method for simultaneous quantification of these compounds in pharmaceutical dosage forms. Precoated silica gel 60 F254 plate was used as stationary phase. The separation was carried out using Glacial acetic acid:Cyclohexane:Methanol:(80:15:5 v/v/v as mobile phase. The proposed method was found to be fast, accurate, precise, reproducible and rugged and can be used for a simultaneous analysis of these drugs in combined formulations.

  5. Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

    Zhang, Yi; Tay, JooHwa

    2015-04-09

    Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. A simple spectrophotometric determination of diclofenac sodium in commercial dosage forms using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)

    Raza, A.; Ansari, T.M.; Niazi, S.B.; Bukhari, S.I.H.

    2005-01-01

    A rapid, simple and sensitive spectrophotometric method has been developed for the determination of diclofenac sodium in pure and tablet formulations. The method depends on the charge-transfer complexation between diclofenac sodium as n-electron donor with 2,3-dichloro-,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile medium as pi-acceptor to give a colored complex which absorbs maximally at 545 nm. Beer's law has been obeyed in the concentration range of 13-275 micro gram ml/sup -1/ with molar absorptivity of 2.5 x 10/sup 3/L mole/sup -1/cm/sup -1/. The proposed method is precise, accurate and specific for routine quantitative analysis of the drug in bulk and dosage forms. (author)

  7. Comparative pharmacokinetic study of dosage forms with morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate

    I. V. Bushueva

    2014-12-01

    Full Text Available Using mathematical models of income distribution and excretion of drugs greatly enhances the interpretation of the results of biopharmaceutical research. Pharmacokinetic modeling makes it possible to quantify the biological assessment of pharmaceutical factors, opens the possibility of a science-based regulation of the kinetics of substances introduced through targeted changesof pharmaceutical factors. Results of the study of kinetic models are used to solve some practical problems associated with pharmacological and clinical trials of medicines. Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate is new organic compound from the 1,2,4-triazole group obtained at the Department of Inorganic Chemistry, Zaporozhye State Medical University. The substance has antioxidant and anti-ischemic action, low toxicity. Aim of this work is to study the kinetics of absorption of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate developed formulations. MATERIALS AND METHODS Pharmacokinetic studies of oral and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate was performed on Chinchilla rabbits weighing an average of 2.5 kg, divided into three groups. The third group for comparison was administered a 1% injectable solution of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate intravenously. Substance dose was 0.1 g and 0.5 g per kg of animal body weight, which were administered once. Sampling from the auricular vein of the rabbits was performed at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180 minutes after oral administration and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate and after 3, 5, 10, 15, 20, 30, 40, 50 and 60 minutes after intravenous injection. Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate concentration in serum was adjusted spectrophotometrically. Results.Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio

  8. Simultaneous determination of atorvastatin calcium and ramipril in capsule dosage forms by high-performance liquid chromatography and high-performance thin layer chromatography.

    Panchal, Hiral J; Suhagia, Bhanubhai N

    2010-01-01

    Two simple and accurate methods to determine atorvastatin calcium and ramipril in capsule dosage forms were developed and validated using HPLC and HPTLC. The HPLC separation was achieved on a Phenomenex Luna C18 column (250 x 4.6 mm id, 5 microm) in the isocratic mode using 0.1% phosphoric acid-acetonitrile (38 + 62, v/v), pH 3.5 +/- 0.05, mobile phase at a flow rate of 1 ml/min. The retention times were 6.42 and 2.86 min for atorvastatin calcium and ramipril, respectively. Quantification was achieved with a photodiode array detector set at 210 nm over the concentration range of 0.5-5 microg/mL for each, with mean recoveries (at three concentration levels) of 100.06 +/- 0.49% and 99.95 +/- 0.63% RSD for atorvastatin calcium and ramipril, respectively. The HPTLC separation was achieved on silica gel 60 F254 HPTLC plates using methanol-benzene-glacial acetic acid (19.6 + 80.0 + 0.4, v/v/v) as the mobile phase. The Rf values were 0.40 and 0.20 for atorvastatin calcium and ramipril, respectively. Quantification was achieved with UV densitometry at 210 nm over the concentration range of 50-500 ng/spot for each, with mean recoveries (at three concentration levels) of 99.98 +/- 0.75% and 99.87 +/- 0.83% RSD for atorvastatin calcium and ramipril, respectively. Both methods were validated according to International Conference on Harmonization guidelines and found to be simple, specific, accurate, precise, and robust. The mean assay percentages for atorvastatin calcium and ramipril were 99.90 and 99.55% for HPLC and 99.91 and 99.47% for HPTLC, respectively. The methods were successfully applied for the determination of atorvastatin calcium and ramipril in capsule dosage forms without any interference from common excipients.

  9. Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: An application in quantitative analysis of pharmaceutical dosage forms

    Prathyusha Vemula

    2015-01-01

    Full Text Available To enhance patient compliance toward treatment in diseases like diabetes, usually a combination of drugs is prescribed. Therefore, an anti-diabetic fixed-dose combination of 2.5 mg of linagliptin 500 mg of metformin was taken for simultaneous estimation of both the drugs by reverse phase-high performance liquid chromatography (RP-HPLC method. The present study aimed to develop a simple and sensitive RP-HPLC method for the simultaneous determination of linagliptin and metformin in pharmaceutical dosage forms. The chromatographic separation was designed and evaluated by using linagliptin and metformin working standard and sample solutions in the linearity range. Chromatographic separation was performed on a C 18 column using a mobile phase of 70:30 (v/v mixture of methanol and 0.05 M potassium dihydrogen orthophosphate (pH adjusted to 4.6 with orthophosphoric acid delivered at a flow rate of 0.6 mL/min and UV detection at 267 nm. Linagliptin and metformin shown linearity in the range of 2-12 μg/mL and 400-2400 μg/mL respectively with correlation co-efficient of 0.9996 and 0.9989. The resultant findings analyzed for standard deviation (SD and relative standard deviation to validate the developed method. The retention time of linagliptin and metformin was found to be 6.3 and 4.6 min and separation was complete in <10 min. The method was validated for linearity, accuracy and precision were found to be acceptable over the linearity range of the linagliptin and metformin. The method was found suitable for the routine quantitative analysis of linagliptin and metformin in pharmaceutical dosage forms.

  10. Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

    Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

    2014-06-01

    Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

  11. A Stability-Indicating HPLC-DAD Method for Determination of Stiripentol: Development, Validation, Kinetics, Structure Elucidation and Application to Commercial Dosage Form

    Hany W. Darwish

    2014-01-01

    Full Text Available A rapid, simple, sensitive, and accurate isocratic reversed-phase stability-indicating high performance liquid chromatography method has been developed and validated for the determination of stiripentol and its degradation product in its bulk form and pharmaceutical dosage form. Chromatographic separation was achieved on a Symmetry C18 column and quantification was achieved using photodiode array detector (DAD. The method was validated in accordance with the ICH requirements showing specificity, linearity (r2=0.9996, range of 1–25 μg/mL, precision (relative standard deviation lower than 2%, accuracy (mean recovery 100.08±1.73, limits of detection and quantitation (LOD = 0.024 and LOQ = 0.081 μg/mL, and robustness. Stiripentol was subjected to various stress conditions and it has shown marked stability under alkaline hydrolytic stress conditions, thermal, oxidative, and photolytic conditions. Stiripentol degraded only under acidic conditions, forming a single degradation product which was well resolved from the pure drug with significantly different retention time values. This degradation product was characterized by 1H-NMR and 13C-NMR spectroscopy as well as ion trap mass spectrometry. The results demonstrated that the method would have a great value when applied in quality control and stability studies for stiripentol.

  12. Cascade reactor: granule fabrication processes

    Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

    1985-01-01

    A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

  13. Kinetic and equilibrium studies of the removal of ammonium ions from aqueous solution by rice husk ash-synthesized zeolite Y and powdered and granulated forms of mordenite

    Yusof, Alias Mohd; Keat, Lee Kian; Ibrahim, Zaharah; Majid, Zaiton Abdul; Nizam, Nik Ahmad

    2010-01-01

    The removal of ammonium from aqueous solutions using zeolite NaY prepared from a local agricultural waste, rice husk ash waste was investigated and a naturally occurring zeolite mordenite in powdered and granulated forms was used as comparison. Zeolite NaY and mordenite were well characterized by powder X-ray diffraction (XRD), energy dispersive X-ray (EDX) analysis and the total cation exchange capacity (CEC). CEC of the zeolites were measured as 3.15, 1.46 and 1.34 meq g -1 for zeolite Y, powdered mordenite and granular mordenite, respectively. Adsorption kinetics and equilibrium data for the removal of NH 4 + ions were examined by fitting the experimental data to various models. Kinetic studies showed that the adsorption followed a pseudo-second-order reaction. The equilibrium pattern fits well with the Langmuir isotherm compared to the other isotherms. The monolayer adsorption capacity for zeolite Y (42.37 mg/g) was found to be higher than that powdered mordenite (15.13 mg/g) and granular mordenite (14.56 mg/g). Thus, it can be concluded that the low cost and economical rice husk ash-synthesized zeolite NaY could be a better sorbent for ammonium removal due to its rapid adsorption rate and higher adsorption capacity compared to natural mordenite.

  14. Development and Validation of a Rapid RP-HPLC Method for the Determination of Venlafaxine Hydrochloride in Pharmaceutical Dosage forms using Experimental Design

    Vanita Somasekhar

    2009-01-01

    Full Text Available The objective of the current study was to develop a simple, accurate, precise and rapid reversed-phase HPLC method and subsequent validation as per ICH guidelines for the determination of venlafaxine hydrochloride in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a 5 μm Varian® Microsorb-MV 100 C18 column (250 mmx4.6 mm at ambient temperature. A 23 factorial design consisting of 3 factors at 2 levels was set up to standardize the chromatographic conditions. A numerical optimization technique employing the desirability approach was used to locate the optimum chromatographic conditions. The optimum mobile phase consisted of acetonitrile, 0.04 M potassium dihydrogen phosphate buffer and methanol (45:25:30, v/v, with pH adjusted to 5.5 using 10% phosphoric acid solution. The mobile phase was delivered isocratically at a flow rate of 1 mL/min with UV detection at 224 nm. The calibration plots constructed using the optimized chromatographic conditions displayed good linear relationship in the concentration range of 1-50 μg/mL with r=0.9992. The method was validated for precision, accuracy, robustness and recovery. The minimum detectable and minimum quantifiable amounts were found to be 0.568 and 1.72 μg/mL, respectively and the method was found to be reproducible from the statistical data generated. Venlafaxine hydrochloride was eluted at 3.43 min

  15. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

  16. Optimization of Forced Degradation Using Experimental Design and Development of a Stability-Indicating Liquid Chromatographic Assay Method for Rebamipide in Bulk and Tablet Dosage Form

    Sandeep SONAWANE

    2016-09-01

    Full Text Available A novel stability-indicating RP-HPLC assay method was developed and validated for quantitative determination of rebamipide in bulk and tablet dosage form. Rebamipide (drug and drug product solutions were exposed to acid and alkali hydrolysis, thermal stress, oxidation by hydrogen peroxide and photodegradation. Experimental design has been used during forced degradation to determine significant factors responsible for degradation and to obtain optimal degradation conditions. In addition, acid and alkali hydrolysis was performed using a microwave oven. The chromatographic method employed the HiQ sil C-18HS (250 × 4.6 mm; 5 μm column with mobile phase consisting of 0.02 M potassium phosphate (pH adjusted to 6.8 and methanol (40:60, v/v and the detection was performed at 230 nm. The procedure was validated for specificity, linearity, accuracy, precision and robustness. There was no interference observed of excipients and degradation products in the determination of the active pharmaceutical ingredient. The method showed good accuracy and precision (intra and inter day and the response was linear in a range from 0.5 to 5 μg mL−1. The method was found to be simple and fast with less trial and error experimentation by making use of experimental design. Also, it proved that microwave energy can be used to expedite hydrolysis of rebamipide.

  17. A Localized Surface Plasmon Resonance Sensing Method for Simultaneous Determination of Atenolol and Amiloride in Pharmaceutical Dosage Forms and Urine Samples

    Marwa R. El-Zahry

    2018-01-01

    Full Text Available This contribution describes a simple, fast, and sensitive application of localized surface plasmon resonance effect of silver nanoparticles for simultaneous determination of antihypertensive drugs’ mixture atenolol and amiloride in both pharmaceutical dosage forms and in biological samples (urine. Silver nanoparticles were prepared by chemical reduction of silver nitrate using hydroxylamine HCL in an alkaline medium. Application of silver-hydroxylamine nanoparticles (SH NPs provides many advantages including reproducibility, sensitivity, and cost effective way of analyte determination. Amiloride has four amino groups which act as attachment points on the surface of silver nanoparticles resulting in a synergistic effect on the absorption intensity of atenolol, leading to increase the sensitivity of the determination of both compounds. This method shows excellent advantages comparing with the previously reported methods, including accuracy, precision, and selectivity. The linear range of atenolol is 1 × 10−5–1 × 10−4 mol·L−1 and of amiloride is 1 × 10−6–1 × 10−5 mol·L−1. The limit of detection (LOD values of atenolol and amiloride are 0.89 × 10−5 and 0.42 × 10−6 mol·L−1, respectively.

  18. A Simple and Specific Stability- Indicating RP-HPLC Method for Routine Assay of Adefovir Dipivoxil in Bulk and Tablet Dosage Form.

    Darsazan, Bahar; Shafaati, Alireza; Mortazavi, Seyed Alireza; Zarghi, Afshin

    2017-01-01

    A simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation was performed on a C 18 column using a mixture of acetonitrile-citrate buffer (10 mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 mL/min. Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a retention time of 5.8 ± 0.01 min. No interferences were observed from its stress degradation products. The method was validated according to the international guidelines. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 0.5-16 μg/mL; the regression coefficient was 0.9999and the linear regression equation was y = 24844x-2941.3. The detection (LOD) and quantification (LOQ) limits were 0.12 and 0.35 μg/mL, respectively. The results proved the method was fast (analysis time less than 7 min), precise, reproducible, and accurate for analysis of ADV over a wide range of concentration. The proposed specific method was used for routine quantification of ADV in pharmaceutical bulk and a tablet dosage form.

  19. Analytical Method Development and Validation for the Simultaneous Estimation of Abacavir and Lamivudine by Reversed-phase High-performance Liquid Chromatography in Bulk and Tablet Dosage Forms.

    Raees Ahmad, Sufiyan Ahmad; Patil, Lalit; Mohammed Usman, Mohammed Rageeb; Imran, Mohammad; Akhtar, Rashid

    2018-01-01

    A simple rapid, accurate, precise, and reproducible validated reverse phase high performance liquid chromatography (HPLC) method was developed for the determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage forms. The quantification was carried out using Symmetry Premsil C18 (250 mm × 4.6 mm, 5 μm) column run in isocratic way using mobile phase comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a detection wavelength of 245 nm and injection volume of 20 μl, with a flow rate of 1 ml/min. In the developed method, the retention times of ABAC and LAMI were found to be 3.5 min and 7.4 min, respectively. The method was validated in terms of linearity, precision, accuracy, limits of detection, limits of quantitation, and robustness in accordance with the International Conference on Harmonization guidelines. The assay of the proposed method was found to be 99% - 101%. The recovery studies were also carried out and mean % recovery was found to be 99% - 101%. The % relative standard deviation from reproducibility was found to be performance liquid chromatography, UV: Ultraviolet, ICH: International Conference on Harmonization, ABAC: Abacavir, LAMI: Lamivudine, HIV: Human immunodeficiency virus, AIDS: Acquired immunodeficiency syndrome, NRTI: Nucleoside reverse transcriptase inhibitors, ARV: Antiretroviral, RSD: Relative standard deviation, RT: Retention time, SD: Standard deviation.

  20. Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 2: In vitro approach using mechanical force methods.

    Drumond, Nélio; Stegemann, Sven

    2018-06-01

    Predicting the potential for unintended adhesion of solid oral dosage forms (SODF) to mucosal tissue is an important aspect that should be considered during drug product development. Previous investigations into low strength mucoadhesion based on particle interactions methods provided evidence that rheological measurements could be used to obtain valid predictions for the development of SODF coatings that can be safely swallowed. The aim of this second work was to estimate the low mucoadhesive strength properties of different polymers using in vitro methods based on mechanical forces and to identify which methods are more precise when measuring reduced mucoadhesion. Another aim was to compare the obtained results to the ones achieved with in vitro particle interaction methods in order to evaluate which methodology can provide stronger predictions. The combined results correlate between particle interaction methods and mechanical force measurements. The polyethylene glycol grades (PEG) and carnauba wax showed the lowest adhesive potential and are predicted to support safe swallowing. Hydroxypropyl methylcellulose (HPMC) along with high molecular grades of polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) exhibited strong in vitro mucoadhesive strength. The combination of rheological and force tensiometer measurements should be considered when assessing the reduced mucoadhesion of polymer coatings to support safe swallowing of SODF. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Validated RP-HPLC Method for the Assay of Etoricoxib (A Non-Steroidal Anti-Inflammatory Drug in Pharmaceutical Dosage Forms

    Srinivasu Topalli

    2012-01-01

    Full Text Available A simple, accurate, sensitive and reproducible reverse phase high performance liquid chromatographic method has been developed for the quantitative determination of Etoricoxib in pharmaceutical dosage forms. The assay was performed on Hypersil ODS C-18 (250 x 4.6 mm., 5µm particle size column using acetonitrile and potassium dihydrogen phosphate buffer (pH 4.2 (46:54 % v/v as mobile phase with UV detection at 280 nm (flow rate 1.2 ml/min. Bromhexine was used as an internal standard. Quantization was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection (LOD and the limit of quantification (LOQ were 0.0704 µg ml-1 and 0.2134 µg ml-1 respectively. Each analysis required no longer than 10 minutes. The calibration curve was linear over the concentration range from 0.5-85.0 µg ml-1. The retention times of Etoricoxib and Bromhexine were found to be 3.083 and 7.631 minutes respectively. The proposed method was validated according to the ICH guidelines and can be used successfully to analyse marketed formulations.

  3. Stability-Indicating RP-UPLC Method for the Simultaneous Determination of Potential Degradation and Process Impurities of Amlodipine Basylate and Benazepril HCl in Pharmaceutical Dosage Form

    Gajanan B. Kasawar

    2014-10-01

    Full Text Available A stability-indicating RP-UPLC method was developed for the quantification of related impurities of amlodipine basylate (AB and Benazepril hydrochloride (BH in solid pharmaceutical dosages form. The chromatographic separation employs a C18 column using a gradient elution, being solvent-A (1.36 g of potassium dihydrogen phosphate dissolved in one liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent-B (acetonitrile delivered at a flow rate of 0.3 mL min-1. The analytes were detected and quantified at 217 nm and 240 nm using photo diode-array detector. The method was validated demonstrating to be accurate and precise within the corresponding linear range of all components. The stability of the method was investigated under different stress conditions including hydrolytic, oxidative, exposed to photolytic, humidity and thermal as recommended by ICH guidelines. Relevant degradation was found under hydrolytic and oxidative conditions. Robustness against small modification in mobile phase pH, column oven temperature, flow rate and percentage of the mobile phase composition was ascertained. Lower limit of quantification and detection was also determined. The peak purity indices (purity angle < purity threshold obtained with the aid of PDA detector and satisfactory resolution between related impurities established the specificity of the determination.

  4. Matrix effect on leaching of Bisphenol A diglycidyl ether (BADGE) from epoxy resin based inner lacquer of aluminium tubes into semi-solid dosage forms.

    Lipke, Uwe; Haverkamp, Jan Boris; Zapf, Thomas; Lipperheide, Cornelia

    2016-04-01

    To study the impact of different semi-solid dosage form components on the leaching of Bisphenol A (BPA) and Bisphenol A diglycidyl ether (BADGE) from the epoxy resin-based inner lacquer of aluminium tubes, the tubes were filled with different matrix preparations and stored at an elevated temperature. Despite compliance with the European Standards EN 15348 and EN 15766 on porosity and polymerisation of internal coatings of aluminium tubes, the commercially available tubes used in the study contained an increased amount of polymerisation residues, such as unbound BPA, BADGE and BADGE derivatives in the lacquer, as determined by acetonitrile extraction. Storage of Macrogol ointments in these tubes resulted in an almost quantitative migration of the unbound polymerisation residues from the coating into the ointment. In addition, due to alterations observed in the RP-HPLC chromatograms of the matrix spiked with BADGE and BADGE derivatives it is supposed that the leachates can react with formulation components. The contamination of the medicinal product by BPA, BADGE and BADGE derivatives can be precluded by using aluminium tubes with an internal lacquer with a low degree of unbound polymerisation residues. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Development and Validation of a Precise, Single HPLC Method for the Determination of Tolperisone Impurities in API and Pharmaceutical Dosage Forms.

    Raju, Thummala Veera Raghava; Seshadri, Raja Kumar; Arutla, Srinivas; Mohan, Tharlapu Satya Sankarsana Jagan; Rao, Ivaturi Mrutyunjaya; Nittala, Someswara Rao

    2013-01-01

    A novel, sensitive, stability-indicating HPLC method has been developed for the quantitative estimation of Tolperisone-related impurities in both bulk drugs and pharmaceutical dosage forms. Effective chromatographic separation was achieved on a C18 stationary phase with a simple mobile phase combination delivered in a simple gradient programme, and quantitation was by ultraviolet detection at 254 nm. The mobile phase consisted of a buffer and acetonitrile delivered at a flow rate 1.0 ml/min. The buffer consisted of 0.01 M potassium dihydrogen phosphate with the pH adjusted to 8.0 by using diethylamine. In the developed HPLC method, the resolution between Tolperisone and its four potential impurities was found to be greater than 2.0. Regression analysis showed an R value (correlation coefficient) of greater than 0.999 for the Tolperisone impurities. This method was capable of detecting all four impurities of Tolperisone at a level of 0.19 μg/mL with respect to the test concentration of 1000 μg/mL for a 10 µl injection volume. The tablets were subjected to the stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in base hydrolysis, water hydrolysis, and oxidation. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 100%. The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.

  6. Brand versus generic dispensing trend for ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg (oral dosage forms) among pharmacies of Karachi, Pakistan.

    Zehra, Fatima; Naqvi, Atta Abbas; Tasneem, Sumbul; Ahmad, Rizwan; Ahmad, Niyaz; Shamsi, Adnan Zia; Asghar, Naqiya Ali; Khan, Ghufran Ullah

    2017-01-01

    Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month. It was aimed at gathering response from different pharmacies to understand the brand versus generic dispensing trend of ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg oral dosage forms. The study employed convenience sampling and used a survey checklist. The data gathered was entered in SPSS version 22. The mean price per tablet for ciprofloxacin brand and generic was reported at Pakistani Rupees (PKR) 48.44 and PKR 26.85, respectively. The trend for dispensing ciprofloxacin highlighted a split in the market between brand (51%) and generic (49%). For levofloxacin brand and generic, the price per tablet was reported at PKR 36.50 and PKR 36.15 respectively, and despite same price, the market was dominated by generic levofloxacin (92%). Due to a price difference between brand and generic moxifloxacin, i.e., PKR 129.44 and PKR 71.91, respectively, the market was mostly occupied by the generic form (75%). Pricing mechanism must be revisited, and the authorities should take stern actions against any illegitimate price hike. The surging burden of drug expenditure on poorer sections of the society must be addressed by the government on an urgent basis.

  7. A study of knowledge, attitude and practice regarding administration of pediatric dosage forms and allied health literacy of caregivers for children

    Amrita Sil

    2017-01-01

    Full Text Available Context: Caregivers of sick children have to be careful with medicine dosing and giving medicines to a reluctant child can be challenging. Aim: To assess the knowledge, attitude, and practices of caregivers regarding pediatric medicine administration and health literacy allied to this task. Settings and Design: This cross-sectional study was carried out on outpatient and inpatient basis in the pediatrics department of a teaching hospital over 6 months. Subjects and Methods: Data regarding sociodemographic profile of patient and caregiver, idea regarding pediatric dosage forms, dosing of medicines, and medication errors during administration were recorded from 377 caregivers. Reconstitution of dry powder and measurement of 5 mL liquid medicine using measuring cup of the medicine phial was demonstrated by the caregivers. Statistical Analysis: Association assessed by point biserial correlation and Spearman's rank correlation. Results: Majority of the primary caregivers surveyed were young, educated, homemaker mothers. Liquid medicines were used maximally (88.9%. Majority (87.3% of the caregivers used standardized dosing instruments to measure liquids and reconstitution (85.9%, and teaspoon measurement task (91% was performed satisfactorily by most. Some potentially wrong practices (e.g., adding medicine to milk, redilution of reconstituted medicine, and storing beyond the recommended period were recorded. Medication errors were reported by 44.5% caregivers, significantly more in the outpatient setting. Although the statistical correlation was weak, the chance of medication error was less, and the precision of measurement was better with increasing education of the caregiver. Conclusions: Physicians need to be aware of the limitations of knowledge and the possibility of wrong administration practices among caregivers of children. Remedial measures in this regard can reduce the risk of medication errors.

  8. Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

    Sutirtho Mukhopadhyay

    2011-01-01

    Full Text Available Objective : Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods : Simultaneous determination of related substances was performed on Kromasil C 18 analytical column (250 × 4.6 mm; 5΅m pertical size column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v was used at a flow rate of 1.0 ml min−1 . UV detection was performed at 270 nm. Results : During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions : HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets.

  9. A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method

    Md. Sarowar Jahan

    2014-01-01

    Full Text Available A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and system suitability. Forced degradation study was validated according to International Conference on Harmonisation (ICH. For this, an isocratic condition of mobile phase comprising phosphate buffer (pH 6.8 and acetonitrile in a ratio of 65:35, v/v at a flow rate of 0.7 mL/minute over RP C18 (octadecylsilane (ODS, 150 × 4.6 mm, 5 μm, Phenomenex Inc. column at ambient temperature was maintained. The method showed excellent linear response with correlation coefficient ( R 2 values of 0.999 and 1.0 for paracetamol and ibuprofen respectively, which were within the limit of correlation coefficient ( R 2 > 0.995. The percent recoveries for two drugs were found within the acceptance limit of (97.0-103.0%. Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (%RSD ≤ 2.0. Forced degradation of the drug product was carried out as per the ICH guidelines with a view to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions. The degradation of ibuprofen was within the limit (5-20%, according to the guideline of ICH, while paracetamol showed <20% degradation in oxidation and basic condition.

  10. A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method.

    Jahan, Md Sarowar; Islam, Md Jahirul; Begum, Rehana; Kayesh, Ruhul; Rahman, Asma

    2014-01-01

    A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP) guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and system suitability. Forced degradation study was validated according to International Conference on Harmonisation (ICH). For this, an isocratic condition of mobile phase comprising phosphate buffer (pH 6.8) and acetonitrile in a ratio of 65:35, v/v at a flow rate of 0.7 mL/minute over RP C18 (octadecylsilane (ODS), 150 × 4.6 mm, 5 μm, Phenomenex Inc.) column at ambient temperature was maintained. The method showed excellent linear response with correlation coefficient (R (2)) values of 0.999 and 1.0 for paracetamol and ibuprofen respectively, which were within the limit of correlation coefficient (R (2) > 0.995). The percent recoveries for two drugs were found within the acceptance limit of (97.0-103.0%). Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (%RSD) ≤ 2.0. Forced degradation of the drug product was carried out as per the ICH guidelines with a view to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions. The degradation of ibuprofen was within the limit (5-20%, according to the guideline of ICH), while paracetamol showed degradation in oxidation and basic condition.

  11. Stability indicating RP-HPLC method development and validation for the simultaneous determination of aminexil and minoxidil in pharmaceutical dosage form.

    Siddiraju, S; Sahithi, M

    2015-03-01

    The objective of the present work is to develop stability indicating high-performance liquid chromatographic method for the simultaneous determination of aminexil and minoxidil in pharmaceutical dosage form. The chromatographic separation was achieved with BDS Hypersil C18 column (250 mm×4.6 mm×5 μ) as stationary phase and phosphate buffer and acetonitrile (78:22) as mobile phase. The method was employed by using a flow rate of 1.1 mL/min kept at 30°C. The detection wavelength was kept at 238 nm by using photo-diode array detector. The retention times of the aminexil and minoxidil were found to be 2.3 min and 3.9 min, respectively. The method developed was validated in accordance with ICH guidelines with respect to the stability indicating capacity of the method including system suitability, accuracy, precision, linearity, range, limit of detection, limit of quantification and robustness. The linearity responses of aminexil and minoxidil were found to be in the concentration ranges of 18.75-112.5 μg/mL and 25-150 μg/mL, respectively. The LOD and LOQ values for aminexil were found to be 0.31 and 0.92 μg/mL and minoxidil were found to be 0.03 and 0.10 μg/mL respectively. The percentage recoveries for both the drugs were found in the range of 98-101%. This method is accurate, precise and sensitive; hence, it can be employed for routine quality control of aminexil and minoxidil in pharmaceutical industries and drug testing laboratories. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Simultaneous determination of nortriptyline hydrochloride and fluphenazine hydrochloride in microgram quantities from low dosage forms by liquid chromatography–UV detection

    Safwan Ashour

    2012-12-01

    Full Text Available A novel method for the simultaneous high-performance liquid chromatographic determination of nortriptyline hydrochloride and fluphenazine hydrochloride was developed and validated. Fluvastatin sodium was used as internal standard. The determination was performed on a Hypersil Gold C8 column (250 mm × 4.6 mm i.d., 5 μm particle size at 25 °C; the mobile phase, consisting of a mixture of formic acid (0.1 M, pH 2.16-methanol (33:67, v/v, was delivered at a flow rate of 1.1 mL/min and detector wavelength at 251 nm. The retention time of nortriptyline, fluphenazine and fluvastatin was found to be 5.11, 8.05 and 11.38 min, respectively. Linearity ranges were 5.0–1350.0 and 10.0–1350.0 μg/mL with limit of detection values of 0.72 and 0.31 μg/mL, for nortriptyline and fluphenazine, respectively. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. Correlation coefficients (r2 of the regression equations were greater than 0.999 in all cases. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of nortriptyline and fluphenazine. Keywords: Nortriptyline hydrochloride, Fluphenazine hydrochloride, Liquid chromatography, Pharmaceutical dosage form

  13. Development and validation of RP-HPLC method for determination of famotidine and its application in quality control of different pharmaceutical dosage forms

    Hassan, S.S.; Ayub, M.; Ishtiaq, S.; Ahmad; I; Khalid, N.

    2013-01-01

    A precise and fast novel high-performance liquid chromatography method was developed and validated for the quantitative determination of Famotidine (FMT) in commercially available pharmaceutical dosage forms. An Agilent 1200 Series High Performance Liquid Chromatography (HPLC) system having the column C 1 8 (5 micro m particle size, 150*4.6 mm) was used in this study and detection (diode array detector) was made at 280 nm. The mobile phase was acetonitrile, distilled water, triethylamine and phosphoric acid (49.9:49.9:0.1:0.1, v/v), isocratic elution under ambient temperature at flow rate of 1.5 mL min/sup -1/ with injection volume 5 micro L. In this method, the retention times for FMT pure, tablets and suspension were 0.787 min, 0.789 min and 0.839 minutes respectively. The new method was validated by different validation parameters. The procedure provided a linear response over the concentration range of 0.1-1.0 mg mL/sup -1/ (r/sup 2/ =0.998) and equation was y=3902.6+18.651. The mean % recovery for inter-day (96.56%) and intra-day (97.36%) assuring a good precision and accuracy was 96-98%. The method was found to be very rapid and the overall assay time was less than 2 minutes and the results obtained were accurate, precise and selective enough to allow the determination of FMT in the presence of certain excipients. (author)

  14. Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms.

    Krishnaiah, Ch; Vishnu Murthy, M; Kumar, Ramesh; Mukkanti, K

    2011-03-25

    A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at 250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r(2)>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Effects of x irradiation on the postnatally-forming granule cell populations in the olfactory bulb, hippocampus, and cerebellum of the rat

    Bayer, S.A.; Altman, J.

    1975-01-01

    Beginning on the second postnatal day, either two (2X group), four (4X group) or six (6X group) daily or alternate daily exposures to low-level x irradiation (150 to 200 R) were used to interfere with the acquisition of granule cells in the olfactory bulb, hippocampus, and cerebellum of the rat. At 60 days of age, the relationship between post-irradiation recovery and permanent granule cell loss was assessed with two quantitative techniques. First, the total number of granule cells was determined to estimate the magnitude of permanent loss. Secondly, the number of labeled granule cells were counted on day 60 after a 3 H-thymidine injection given on either day 15 or on day 20 to estimate differential rates of cell proliferation during the recovery period. Permanent loss of granule cells was sustained in all regions by all schedules of irradiation. The time for the most effective exposures was earlier in the hippocampus and olfactory bulb than in the cerebellum. In all regions, both the irradiated groups and the controls showed a decrease in the level of cell proliferation between 15 and 20 days. The number of cells that could be labeled after either the 15 or 20 day injection was below control levels for all groups in the hippocampus, at control levels for all groups in the cerebellum, and either at (2X and 4X) or below (6X) control levels in the olfactory bulb. These results are discussed in the light of the formation time of the granule cells in each region

  16. Effects of x-irradiation on the postnatally-forming granule cell populations in the olfactory bulb, hippocampus, and cerebellum of the rat

    Bayer, S.A.; Altman, J.

    1975-01-01

    Beginning on the second postnatal day, either two (2X group), four (4X group) or six (6X group) daily or alternate daily exposures to low-level x irradiation (150-200 r) were used to interfere with the acquisition of granule cells in the olfactory bulb, hippocampus, and cerebellum of the rat. At 60 days of age, the relationship between post-irradiation recovery and permanent granule cell loss was assessed with two quantitative techniques. First, the total number of granule cells was determined to estimate the magnitude of permanent loss. Secondly, the number of labeled granule cells were counted on day 60 after a 3 H-thymidine injection given on either day 15 or on day 20 to estimate differential rates of cell proliferation during the recovery period. Permanent loss of granule cells was sustained in all regions by all schedules of irradiation. The time for the most effective exposures was earlier in the hippocampus and olfactory bulb than in the cerebellum. In all regions, both the irradiated groups and the controls showed a decrease in the level of cell proliferation between 15 and 20 days. The number of cells that could be labeled after either the 15 or 20 day injection was below control levels for all groups in the hippocampus, at control levels for all groups in the cerebellum, and either at (2X and 4X) or below (6X) control levels in the olfactory bulb. These results are discussed in the light of the formation time of the granule cells in each region

  17. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    Rybachuk VD

    2016-12-01

    Full Text Available Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms of granules: isodiametric and nonisodiametric. The first group of particles forms has globular shape with a smooth surface and the proportion in which the length, thickness and height are about the same. They are usually made by fluidized bed granulation, spray drying, pelletizing and granulation in dragee pan. Granules of nonisodiametric form in which length is several times the width and height are made mostly by extrusion and compacting. The geometrical parameters of obtained granules are affected by the properties of raw materials, the granulation modes, type and amount of added humidifier and so on. The shape and size of granules, from a technological point of view, are the key factors that contribute, except organoleptic characteristics of the product, its technological properties such as particle size distribution, bulk volume, the ability of the material to shrinkage, porosity, fluidity, mechanical strength and so on. Properly selected for specific conditions granulation method is able to provide the finished product with the specified technological parameters depending on the needs. The aim of this work was to study the effect of granulation method and its conditions on the kinetics of growth of the natural zeolite granules and some quality characteristics of obtained granules. Material & methods. As objects of study served the natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch paste and solution of polyvinylpyrrolidone (PVP

  18. Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

    Guo S

    2016-04-01

    over 2.5-fold compared to RTV solution. Conclusion: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development. Keywords: ritonavir, pediatric formulation, taste, pharmacokinetics, lipid formulation, drug loading

  19. QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

    Ke Li

    2017-01-01

    Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

  20. Low cost technology for the rapid and safe in-house (hospital-based) preparation of dual - radiotherapeutic (Rx) and radiodiagnostic (Dx) - dosage forms of high specific activity 131I-mIBG for clinical application

    Noronha, O.P.D.; Sonawane, G.A.; Samuel, A.M.

    1998-01-01

    Radioiodinated mIBG is finding increasing utility in nuclear medicine. However, its widespread use in developing countries is precluded by logistic constraints owing to the relative instability of the labelled molecule with respect to time and temp., and high costs. This prompted us to develop a low cost in-house batch process technology that could be used for the small-scale preparation of 131 I-mIBG even in a less equipped hospital-based radiopharmacy. The production of large amounts of 131 I-mIBG for clinical use requires sophisticated infrastructure (a scarce resource) to contain / safeguard against internal and external radiation exposures. We have indigenously designed a semi-automated, self-shielded, remote-controlled and safe microplant + process assemblies using easily accessible and cheap inputs, and developed the complete technology for the rapid and safe production of dual dosage forms of 131 I-mIBG, a radiotherapeutic (R x ) single dosage form of high activity along with 1-3 low activity radiodiagnostics (D x ) as multidosage forms. The radioiodide exchange reaction was effected in the solid / melt phase at 190 deg. C in 1.0 h. The radiolabelling yield was ∼80.0-86.0%, and the radiochemical purity > 99.5% and specific activity of R x /D x =900-1300/60-800 MBq ( x dosage forms at 3 weeks. The dosage forms (especially R x ) were only made against firm patient appointment(s). Thus far we have prepared 14 R x (49.0 GBq) and 70 + 14 batches (43.43 GBq) of (∼150 nos.) D x forms, and used them in 14 and > 1100 patients respectively. (author)

  1. Effect of surfactants, gastric emptying, and dosage form on supersaturation of dipyridamole in an in vitro model simulating the stomach and duodenum.

    Mitra, A; Fadda, H M

    2014-08-04

    The purpose of this study was to investigate the influence of gastric emptying patterns, surfactants, and dosage form on the supersaturation of a poorly soluble weakly basic drug, dipyridamole, using an in vitro model mimicking the dynamic environment of the upper gastrointestinal tract, and, furthermore, to evaluate the usefulness of this model in establishing correlations to in vivo bioavailability for drugs with solubility/dissolution limited absorption. A simulated stomach duodenum model comprising four compartments was used to assess supersaturation and precipitation kinetics as a function of time. It integrates physiologically relevant fluid volumes, fluid transfer rates, and pH changes of the upper GI tract. Monoexponential gastric emptying patterns simulating the fasted state were compared to linear gastric emptying patterns simulating the fed state. The effect of different surfactants commonly used in oral preparations, specifically, sodium lauryl sulfate (SLS), poloxamer-188, and polysorbate-80, on dipyridamole supersaturation was investigated while maintaining surface tension of the simulated gastric fluids at physiological levels and without obtaining artificial micellar solubilization of the drug. The supersaturation behavior of different dose strengths of dipyridamole was explored. Significant levels of dipyridamole supersaturation were observed in the duodenal compartment under all the different in vivo relevant conditions explored. Dipyridamole supersaturation ratios of up to 11-fold have been observed, and supersaturation has been maintained for up to 120 min. Lower duodenal concentrations of dipyridamole were observed under linear gastric emptying patterns compared to mononexponential gastric emptying. The mean duodenal area under concentration-time curves (AUC60min) for the dipyridamole concentration profile in the duodenal compartment is significantly different for all the surfactants explored (P stomach duodenum model can provide a reliable and

  2. Influence of the segregation of the granulate from the radwaste-mortar mixture from on the {sup 137}Cs leach-rate; Uticaj segregacije granulata iz sastava betonske - RAO forme na izluzivanje Cs{sup 137}

    Peric, A; Plecas, I; Pavlovic, R; Pavlovic, S [Institute of Nuclear Sciences VINCA, Belgrade (Yugoslavia)

    1994-07-01

    In this paper. influence of the segregation of the granulate, presented in the radwaste-mortar matrix formulation, on the {sup 137}Cs, immobilized in the waste form, leach-rate is presented. {sup 137}Cs leach-rates of the two inspected groups of the radwaste-mortar mixture samples were compared, where the first group of the orthocylinder shaped samples was treated due to the Standard Hespe's method and the second group was treated using modified Hespe's method. In the prolonged experimental time, both groups have obtained leach-rate values that are nearly the same, striving to the saturation leach-rate values. This fact indicates that the leaching of the radionuclide as a consequence of the granulate segregation process is in same way rebuilt, as a result of the completed hydratation of the mortar matrix, and 'self healing' of the new open pores and cavities (author)

  3. Effect of binders on 500mg metformin hydrochloride tablets produced by wet granulation

    LUCIANA CATIA BLOCK

    2009-12-01

    Full Text Available Metformin hydrochloride (MH is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch 1500® /PVP K30®, PVP K30® and PVP K90® in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr’s Index (CI and the Hausner ratio (HR. Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500® /PVP K30® mixtures were best for producing 500 mg MH tablets. Keywords: Metformin hydrochloride. Tablets. Wet granulation. Binders.

  4. Regularities of formation of granules at granulation of powdered materials in drum devices

    Kelbaliyev, G.I; Samedli, V.M.

    2008-01-01

    Full text:Granulation of powdered materials in the presence of binding agent is widely used in the most multi-tankage productions of chemical, food, pharmaceutical, metallurgical and agrarian technology. Granulation of powdered materials with participation of liquid phase is carried out in screw, disk, plase-shaped and drum devices and also in devices with mixers. In all cases a formation and growth of granules takes place owing to wetting of separate particles of powder leading to agglomeration and coagulation of particles in their contact with each other. It is apparent that in early stage of granule formation a growth and formation of granules takes place owing to adherence of small particles and agglomerates to larger granules. The content of liquid phase owing to which are appeared adhesive, capillary and surface forces, keeping particles on surface of granule exerts an essential influence on process of granule formation. Besides composition of mixture, its moisture and physical-chemical properties of initial components a mixing frequency degree of filling and angle of inclination of the device, ratio of liquid and hard phases which defines finally qualitative characteristics of the process exert an essential influence on formation of granules as a result of agglomeration of particles of powder. Powder lamination on granule surface is as consequence of its consolidation whereas as a result of consolidation and compression, a binding agent containing in pores squeezed out to a surface, which increases a possibility and probability of further sticking of dry particles of powder. In all cases the further growth and completeness of form of granule is determined by distribution of concentration of binding agent in volume of granule, i.e. moisture content or moisture of granule surface

  5. Shelf-life evaluation of Kaṃsaharītakī avaleha and its granules: A preliminary study.

    Khemuka, Nidhi; Galib, R; Patgiri, B J; Prajapati, Pradeep Kumar

    2015-01-01

    Savīryatā-avadhi (shelf life) of different Ayurvedic dosage forms is described in Śārṅgadharasaṃhitā. Though the concepts have a strong background, we seek to re-evaluate the age old concepts by following current norms. An attempt has been made in the present study to evaluate shelf-life of Kaṃsaharītakī avaleha and its granules. Raw materials were procured from Pharmacy, Gujarat Ayurved University, Jamnagar and utilized after proper authentication in pharmacognosy lab. The avaleha and its granules were prepared in the departmental laboratory following classical guidelines and subjected to accelerated stability studies. Both the products were found to be free from microbial contamination. Heavy metals were within the prescribed limit. Changes in physico-chemical profiles at different intervals are insignificant. On extrapolation of the observations, the shelf life of avaleha was found to be18 months and 27 months to the granules. Stability of granules was found to be comparatively higher than the avaleha. This observation may be exclusive to Kaṃsaharītakī avaleha. Studies on other avalehas and their granules need to be carried out to confirm this preliminary observation.

  6. APPLICATION OF GRANULATION TECHNOLOGY IN VARIOUS INDUSTRIES

    B. V. YEGOROV

    2017-10-01

    Full Text Available Science and practice proved the high efficiency of granulated mixed fodders. This article presents an overview of granulation technologies for various industries. This article discusses the application of granulation technologies in various industries. The processes of granulation are mass technological processes currently used in a wide range of industries: feed industry, food industry, pharmaceutical industry, fertilizer production, polyethylene, metal production, mining, etc. A wide range of different materials are granulated, including chemicals, iron ore, mixed fodder, and much more. Granulation is a process of pressing or shaping a material in the form of granulesGranulation is widely used in the production of pigments, dyes, synthetic detergents, catalysts, plastics, soot, chemical reagents, etc. The use of granular raw materials in the metallurgical industry helps not only to mechanize processes, but also to increase their intensity by increasing the contact surface of interacting media. Granular fertilizers retain their properties for a long time. In the mining industry, granulation processes are used at the stage of preparation and enrichment of raw materials and release of the finished product.  Particular attention is paid to the feed industry. Granulation allows to ensure stable homogeneity, to improve sanitary and hygienic parameters, to increase nutritional value, to increase the storage period, improve the physical properties. However, despite all the advantages, the existing granulation production lines have a relatively high productivity and, at the same time, a high energy intensity. In this regard, this article proposes a technology for improving the granulation of mixed fodders. According to a preliminary literary review, It should be concluded that improving the technology of the granulation process for feed production is a topical issue in the feed industry today. The development of technology for improving the

  7. Development of the fast, simple and fully validated high performance liquid chromatographic method with diode array detector for quantification of testosterone esters in an oil-based injectable dosage form.

    Kozlik, Petr; Tircova, Barbora

    2016-11-01

    Counterfeit steroids are available on the black market, ultimately to consumers who believe they are buying a legitimate pharmaceutical item from the labeled company. In many cases, counterfeit steroids can contain lower doses or some products can be overdosed. This can unwittingly expose users to a significant health risks. The mixture of testosterone propionate, phenylpropionate, isocaproate and decanoate in an oil-based injectable dosage form belongs to the one of the most misused illicit drugs by a variety of athletes. This study developed a new, fast, simple and reliable HPLC method combined with a simple sample preparation step to determine testosterone propionate, phenylpropionate, isocaproate and decanoate in an oil-based injectable dosage form without the use of sophisticated and expensive instrumentation. The developed analytical procedure provides high throughput of samples where LC analysis takes only 6min and sample preparation of oil matrix in one step takes approximately 10min with precision ranging from 1.03 to 3.38% (RSD), and accuracy (relative error %) within ±2.01%. This method was found to be precise, linear, accurate, sensitive, selective and robust for routine application in screening of commercial pharmaceutical products based on content of mentioned testosterone esters in their oil-based injectable dosage form for counterfeit drugs. This method was successfully applied to the analysis of nine samples of commercial testosterone mixtures purchased from various sources and will be further used as an effective screening method for determination of previously mentioned testosterone esters in samples confiscated by Institute of Forensic Science (Slovakia) during the illegal trade. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Multi-unit dosage formulations of theophylline for controlled release applications.

    Uhumwangho, Michael U; Okor, Roland S

    2007-01-01

    The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The

  9. The life cycle of platelet granules [version 1; referees: 2 approved

    Anish Sharda

    2018-02-01

    Full Text Available Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types—dense granules, α-granules, and lysosomes—although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans-Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  10. Granulation of snow: From tumbler experiments to discrete element simulations

    Steinkogler, Walter; Gaume, Johan; Löwe, Henning; Sovilla, Betty; Lehning, Michael

    2015-06-01

    It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded -1∘C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed.

  11. Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 3: Review of in vitro and in vivo methods used to predict esophageal adhesion and transit time.

    Drumond, Nélio; Stegemann, Sven

    2018-05-01

    The oral cavity is frequently used to administer pharmaceutical drug products. This route of administration is seen as the most accessible for the majority of patients and supports an independent therapy management. For current oral dosage forms under development, the prediction of their unintended mucoadhesive properties and esophageal transit profiles would contribute for future administration safety, as concerns regarding unintended adhesion of solid oral dosage forms (SODF) during oro-esophageal transit still remain. Different in vitro methods that access mucoadhesion of polymers and pharmaceutical preparations have been proposed over the years. The same methods might be used to test non-adhesive systems and contribute for developing safe-to-swallow technologies. Previous works have already investigated the suitability of non-animal derived in vitro methods to assess such properties. The aim of this work was to review the in vitro methodology available in the scientific literature that used animal esophageal tissue to evaluate mucoadhesion and esophageal transit of pharmaceutical preparations. Furthermore, in vivo methodology is also discussed. Since none of the in vitro methods developed are able to mimic the complex swallowing process and oro-esophageal transit, in vivo studies in humans remain as the gold standard. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Mining the granule proteome

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  13. Intercavitary implants dosage calculation

    Rehder, B.P.

    The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

  14. Collages of granulation pictures

    Dunn, R. B.; November, L. J.

    Two small-area selection schemes are applied to CCD observations of solar granulation. One procedure, referred to as mosaic, divides a 128 x 128 array into 64 subarrays of 16 x 16 pixels; the rms contrast of the fine structure is measured and compared in order to develop a mosaic of the subarrays. The second technique, collage, involves calculating rms values within a sliding Gaussian window and gating the pixel into the final image. Methods for assessing seeing quality, which involve the calculation of rms after high-pass filtering, are examined; a simple high-pass filter or an edge-locating function can be utilized for filtering. The rms map is then formed from the convolution of a Gaussian with either the high-pass or the Laplacian filters. The usefulness of the two procedures is demonstrated by applying the mosaic and collage processes to data recorded on July 17, 1983 with a CCD device on the NSO/Sac Peak Vacuum Tower Telescope.

  15. Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

    Pham, Kevin; Li, Diana; Guo, Shujie; Penzak, Scott; Dong, Xiaowei

    2016-03-28

    The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Effect of matrix granulation and wax coating on the dissolution rates ...

    disintegrating) granules consisting of paracetamol (drug) and acrylatemethacrylate copolymer, a matrix forming material. The effect of coating the matrix granules with wax on the drug release profiles was also investigated. The objective was to ...

  17. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  18. UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

    Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

    2012-10-01

    The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

  19. Identification of different shapes, colors and sizes of standard oral dosage forms in diabetes type 2 patients-A pilot study.

    Stegemann, Sven; Riedl, Regina; Sourij, Harald

    2017-01-30

    The clear identification of drug products by the patients is essential for a safe and effective medication management. In order to understand the impact of shape, size and color on medication identification a study was performed in subjects with type 2 diabetes mellitus (T2D). Ten model drugs differentiated by shape, size and color were evaluated using a mixed method of medication schedule preparation by the participants followed by a semi-structured interview. Detection times were fastest for the large round tablet shape and the bi-chromatic forms. Larger size was easier to identify than the smaller sizes except for the bi-chromatic forms. The shape was the major source of errors, followed by the size and the color dimension. The results from this study suggests that color as a single dimension are perceived more effectively by subjects with T2D compared to shape and size, which requires a more demanding processing of three dimension and is dependent on the perspective. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. RESEARCH OF MICROWAVE DRYING OF NATURAL ZEOLITE GRANULES AND ITS INFLUENCE ON THE TECHNOLOGICAL PROPERTIES

    Rybachuk V.D.

    2016-06-01

    Full Text Available Introduction. The wet granulation technique is often used in the preparation of free-flowing granules in the manufacture of tablets and capsules. It is very important that granules obtained by this technology be dried before further processing. And also, it is important that the method of drying is entirely controlled and managed and the result is quite predictable. In recent years, microwave drying of granules make a considerable interest. Microwave drying is especially useful for moisture sensitive materials which are mostly pharmaceutical substances. Microwave drying technology is useful for dosage forms with high purity, since this method provides the possibility of drying in the same container production, which reduces the chance of cross contamination of matter and its direct contact with staff. The aim of this work was to study the effect of microwave radiation on the technological properties of natural zeolite peets compared to traditional convection method and to determine the optimal drying modes and specific humidity of the material. Material & methods. Granules were prepared by wet granulation technology by using a laboratory granulator NG-12. As the humidifier we used potato starch gel and PVP in an amount of 25% by weight of the dry product. The resulting granules were divided into two equal parts and subjected to drying in a microwave oven (Delfa D20MW of installed capacity (119 W, 280 W, 336 W, 462 W, ​​595 W and 700 W and shelf dryer to a residual moisture level of 0.01 g.w./g.d.m. or less. Determination of the specific humidity of granules was carried out by mass loss on drying. Fractional composition of granules was determined using a standard set of sieves with the diameter of the holes 2.0; 1.0; 0.5 and 0.25 mm. The friability of the granules was determined using friabilator Pharma Test PTF 10E / ER, Germany. To characterize the fluidity of granule Carr`s indicator (IC and coefficient Hausnera (HR. Results & discussion

  1. The application dosage of Azolla pinnata in fresh and powder form as organic fertilizer on soil chemical properties, growth and yield of rice plant

    Setiawati, Mieke Rochimi; Damayani, Maya; Herdiyantoro, Diyan; Suryatmana, Pujawati; Anggraini, Derisfha; Khumairah, Fiqriah Hanum

    2018-02-01

    The yield of rice plants is strongly influenced by N fertilizer. Nitrogen in rice plants has roles in vegetative growth, tiller formation and increasing yield through rice protein formation. Nitrogen supplied from organic fertilizers is better than inorganic fertilizers that may have environmental problem effects. Organic fertilizers from Azolla pinnata water fern contain higher N than other organic fertilizers. Symbiosis between A. pinnata and the N-fixing cyanobacteria results in high content of nitrogen, 3 to 5%. A. pinnata can be added to the rice field as organic fertilizer in form of fresh biomass or composted. Composted form can be ground into powder which passes through 100 mesh sieve. Preparation of compost powder of A. pinnata is done to reduce the constraints of voluminous application of organic fertilizers and to improve the efficiency of its use. The objective of this research was to compare the effect of the use of fresh A. pinnata and compost powder of A. pinnata on some soil and plant chemical properties and rice yield. The treatments applied were fresh A. pinnata at the dose of 0, 10 and 20 ton ha-1 and A. pinnata compost powder at 12.5 and 25 kg ha-1. The results showed that incorporation of fresh A. pinnata at 20 tons ha-1 and its compost powder at 25 kg ha-1 increased the available P of soil, plant P content and tiller number, but did not affect the content of organic-C, total soil N, plant N content and rice yield. This study suggested the benefits of A. pinnata compost powder technology in organic fertilization of soil to increase the nutrient content of soil and rice plants.

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

    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.

  3. Development and validation of a reversed-phase HPLC method for simultaneous estimation of clotrimazole and beclomethasone dipropionate in lotion and cream dosage form

    Komal R Dhudashia

    2013-01-01

    Full Text Available Background: The combination of Clotrimazole and Beclomethasone dipropionate is used as anti-fungal and anti-inflammatory for external use in the form of cream and lotion. Aim: A simple, specific, economic, precise, and accurate reversed-phase high performance liquid chromatographic method development for the simultaneous estimation of clotrimazole (CT and beclomethasone dipropionate (BD in lotion and cream formulations. Materials and Methods: The chromatographic separation was achieved on a Kromasil C18 (150 mm × 4.6 mm, 5 μm analytical column. A mixture of acetonitrile-water (70:30, v/v was used as the mobile phase, at a flow rate of 1 ml/min and detector wavelength at 254 nm. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation, and system suitability test as per ICH guideline. Results: The retention time of CT and BD was found to be 5.4 and 4 min, respectively. The linear dynamic ranges were from 2-16 μg/ml and 80-640 μg/ml for BD and CT, respectively. Limit of detection and quantification for BD were 0.039 and 0.12 μg/ml, for CT 1.24 and 3.77 μg/ml, respectively. Conclusions: The developed method was validated and found to be simple, specific, accurate and precise and can be used for routine quality control analysis of titled drugs in combination in lotion and cream formulation.

  4. Development of a validated HPLC method for the quantitative determination of trelagliptin succinate and its related substances in pharmaceutical dosage forms.

    Luo, Zhiqiang; Chen, Xinjing; Wang, Guopeng; Du, Zhibo; Ma, Xiaoyun; Wang, Hao; Yu, Guohua; Liu, Aoxue; Li, Mengwei; Peng, Wei; Liu, Yang

    2018-01-01

    Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is used as a new long-acting drug for once-weekly treatment of type 2 diabetes mellitus (DM). In the present study, a rapid, sensitive and accurate high-performance liquid chromatography (HPLC) method was developed and validated for separation and determination of trelagliptin succinate and its eight potential process-related impurities. The chromatographic separation was achieved on a Waters Xselect CSH™ C 18 (250mm×4.6mm, 5.0μm) column. The mobile phases comprised of 0.05% trifluoroacetic acid in water as well as acetonitrile containing 0.05% trifluoroacetic acid. The compounds of interest were monitored at 224nm and 275nm. The stability-indicating capability of this method was evaluated by performing stress test studies. Trelagliptin succinate was found to degrade significantly in acid, base, oxidative and thermal stress conditions and only stable in photolytic degradation condition. The degradation products were well resolved from the main peak and its impurities. In addition, the major degradation impurities formed under acid, base, oxidative and thermal stress conditions were characterized by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). The method was validated to fulfill International Conference on Harmonisation (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The developed method in this study could be applied for routine quality control analysis of trelagliptin succinate tablets, since there is no official monograph. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Continuous production of controlled release dosage forms based on hot-melt extruded gum arabic: Formulation development, in vitro characterization and evaluation of potential application fields.

    Kipping, Thomas; Rein, Hubert

    2016-01-30

    Controlled release matrices based on gum arabic are prepared by applying a continuous hot-melt extrusion technology: the pre-mixture consisting of gum arabic and the incorporated API is plasticized by a co-rotating twin-screw extruder, an intermediate strand is formed by a round nozzle. Single dosed matrices are prepared by cutting the semi elastic strand with a rotary fly cutter. Paracetamol and phenazone are used as model drug substances. High drug loadings up to 70% can be realized. Matrices are characterized concerning their crystalline structure, in vitro dissolution, disintegration time and various physical parameters including glass transition temperature (Tg). Release characteristic behavior is mainly influenced by erosion of the matrices. At higher drug loadings also diffusion based transport gain importance. The solubility of the API shows an influence on the erosion rate of the matrix and should therefore be considered during formulation development. Tg is mainly influenced by the solubility of the API in the surrounding matrix. High soluble phenazone shows a decrease, whereas paracetamol addition has nearly no influence on the Tg of the polymeric system. Activation energy (EA) of the glass transition is determined via dynamic mechanical analysis. The addition of APIs leads to a reduction of EA indicating an increased molecular movement at Tg region compared to placebo extrudates. X-ray diffraction is used to determine the crystalline state of the extruded matrices and interaction between matrix and incorporated APIs. The production of thin layer matrices is an interesting option to provide a fast drug delivery to the oral cavity. High mechanical strength combined with fast disintegration times can be a great advantage for the development of oro-dispersible tablets. A great benefit of the evaluated processing technology is the simple adaption of the final dose by varying either the cutting length or the diameter of the nozzle resulting in a cost

  6. Study of granulated nickel alloy superplasticity

    Anoshkin, N.F.; Fatkullin, O.Kh.; Ermanok, M.Z.; Sharshagin, N.A.

    1982-01-01

    Peculiarities of the structure and properties of compact material obtained from granules of the EhI 698 and ZhS6U alloys in the form of pressed rods are investigated. It is shown, that granule metallurgy is the most rational technology method, ensuring the receipt of stable fine-grained structure in the initial blank. After appropriate thermal treatment the products obtained by the method of granule metallyrgy have more high strength characteristics at the room temperature and heat resistance, than typical for the products produced by traditional technology. Creation of specialized vertical presses providing low rates of deformation as well as their equipment by vacuum mechanizms which permit to use a tool from molybdenum alloys is necessary for successful introduction into production of the processes of plastic metal working under conditions of superplasticity

  7. Foreign matter identification from solid dosage forms

    Pekka Pajander, Jari; Haugshøj, Kenneth Brian; Bjørneboe, Kathrine

    2013-01-01

    Despite the increased request for robust quality systems, the end product may contain unidentified defects or discoloured regions. The foreign matter has to be monitored, identified and its source defined in order to prevent further contamination. However, the identification task can be complicated......, since the origin and nature of foreign matter are various. The aim of this study is to provide an efficient foreign matter identification procedure for various substances possibly originating from pharmaceutical manufacturing environment. The surface or cross-section of the uncoated and coated tablets...... was analysed by utilization of different analytical techniques, such as light microscopy (LM), scanning electron microscopy in combination with energy dispersive X-ray microanalysis (SEM/EDX), Fourier transform infrared spectroscopy (FT-IR) and time-of-flight secondary ion mass spectrometry (To...

  8. A review on granules initiation and development inside UASB Reactor and the main factors affecting granules formation process

    Habeeb, S.A.; Latiff, Ab Aziz Bin Abdul; Daud, Zawawi Bin; Ahmad, Zulkifli Bin [Civil and Environmental Engineering, University Tun Hussein Onn Malaysia (Malaysia)

    2011-07-01

    Decades of investigations and explorations in the field of anaerobic wastewater treatment have resulted in significant indications about the role importance of sludge granules in biodegradation anaerobic process. It is believed that the development of anaerobic granules is reflecting an important role on the performance of reactor. An overview on the concept of up-flow anaerobic sludge bed (UASB) reactor operation as well as the main parts that reactor consists of is briefly explained in this paper, whereas the major theories of anaerobic granules formation are listed by related researchers. The correlations and compositions of such sludge granule have been specifically explained. It is believed that the extracellular polymer (ECP) is totally responsible of bacterial cell correlations and the formation of bacterial communities in the form of granules. In addition, the dependable factors for the performance of anaerobic granules formation process e.g. temperature, organic loading rate, pH, and alkalinity, nutrients, and cations and heavy metals have been discussed in this paper. Strong evidences proved that the process of gas production in the form of biogas is related to the methanogens activities, which are practically found in the core of granules. The aim of this review is to explore and assess the mechanisms of granules initiation and development inside UASB reactor.

  9. Chromospheric impact of an exploding solar granule

    Fischer, C. E.; Bello González, N.; Rezaei, R.

    2017-06-01

    Context. Observations of multi-wavelength and therefore height-dependent information following events throughout the solar atmosphere and unambiguously assigning a relation between these rapidly evolving layers are rare and difficult to obtain. Yet, they are crucial for our understanding of the physical processes that couple the different regimes in the solar atmosphere. Aims: We characterize the exploding granule event with simultaneous observations of Hinode spectroplarimetric data in the solar photosphere and Hinode broadband Ca II H images combined with Interface Region Imaging Spectrograph (IRIS) slit spectra. We follow the evolution of an exploding granule and its connectivity throughout the atmosphere and analyze the dynamics of a magnetic element that has been affected by the abnormal granule. Methods: In addition to magnetic flux maps we use a local correlation tracking method to infer the horizontal velocity flows in the photosphere and apply a wavelet analysis on several IRIS chromospheric emission features such as Mg II k2v and Mg II k3 to detect oscillatory phenomena indicating wave propagation. Results: During the vigorous expansion of the abnormal granule we detect radially outward horizontal flows, causing, together with the horizontal flows from the surrounding granules, the magnetic elements in the bordering intergranular lanes to be squeezed and elongated. In reaction to the squeezing, we detect a chromospheric intensity and velocity oscillation pulse which we identify as an upward traveling hot shock front propagating clearly through the IRIS spectral line diagnostics of Mg II h&k. Conclusions: Exploding granules can trigger upward-propagating shock fronts that dissipate in the chromosphere. Movies associated to Figs. A.1 and A.2 are available in electronic form at http://www.aanda.org

  10. Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

    Bacher, Charlotte; Olsen, P.M.; Bertelsen, P.

    2008-01-01

    The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10...... size fractions between 0 and 2000 µm and by calculating the demixing potential. Significant inhomogeneous occurrence of calcium carbonate in the size fractions was demonstrated, depending mostly on the particles sizes of sorbitol but also on the morphological forms of calcium carbonate......, the ability of the powder to agglomerate in the roller compactor was demonstrated to be related to the ability of the powder to be compacted into a tablet, thus the most compactable calcium carbonate and the smallest sized sorbitol improved the homogeneity by decreasing the demixing potential....

  11. Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

    Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

  12. Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.

    Coyne, Alyssa N; Yamada, Shizuka B; Siddegowda, Bhavani Bagevalu; Estes, Patricia S; Zaepfel, Benjamin L; Johannesmeyer, Jeffrey S; Lockwood, Donovan B; Pham, Linh T; Hart, Michael P; Cassel, Joel A; Freibaum, Brian; Boehringer, Ashley V; Taylor, J Paul; Reitz, Allen B; Gitler, Aaron D; Zarnescu, Daniela C

    2015-12-15

    RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Assessment of physical properties of granules with paracetamol and caffeine

    Michal Szumilo

    2017-09-01

    Full Text Available Caffeine increases the analgesic properties of acetaminophen and therefore it is reasonable to use both substances together in one drug form in stronger pain. Currently, there are no commercially available pharmaceutical combination products containing acetaminophen and caffeine, which is present as granules. The aim of the study was to obtain twelve different granules with these therapeutic substances and determine the effect of various excipients on the quality of the drug form. All the granules were made by wet granulation. Two types of binders were used: polyethylene glycol 6000 (PEG and polyvinylpyrrolidone K30 (PVP as well as different types of fillers. The physical properties of granules were assessed in accordance to the requirements of the European Pharmacopoeia 8th ed. The highest apparent density was found in preparations containing calcium hydrophosphate (0.609 g/mL and the lowest – containing mannitol (0.353 g/mL as a filler. The Hausner ratio of most prepared granules ranged from 1.05 to 1.11, while the compressibility index ranged from 4.59 to 10.48%. The evaluation of properties of individual granules helped to indicate formulation with good features, which perhaps will be a good alternative to currently available painkillers with caffeine and acetaminophen.

  14. Endotoxin dosage in sepsis

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  15. Formation of tRNA granules in the nucleus of heat-induced human cells

    Miyagawa, Ryu; Mizuno, Rie; Watanabe, Kazunori; Ijiri, Kenichi

    2012-01-01

    Highlights: ► tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. ► tRNAs form the unique granules in the nucleus. ► tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA Met (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA Met was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  16. Collages of granulation pictures

    Dunn, R.B.; November, L.J.

    1985-01-01

    This paper describes two small-area selection schemes that the authors have applied to CCD observations of solar granulation. The first scheme, which the authors call the ''mosaic,'' divides the 128 x 128 array into 64 subarrays each containing 16 x 16 pixels. On each picture in the burst the RMS contrast of the fine structure is measured in each subarray and compared to the corresponding value in a table that contains the highest previous RMS values. The second scheme, which the authors call a ''collage,'' is similar except the RMS value is calculated smoothly within a sliding Gaussian window over the entire scene and the value of an individual pixel is gated into the final collage whenever the RMS contrast at that pixel location exceeds that of all previous frames taken during the burst

  17. Microbial granulation for lactic acid production

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which...... increased, reaching 67 g L-fermenter−1h−1 at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s−1 and 0...

  18. Quercetin topical application, from conventional dosage forms to nanodosage forms.

    Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

    2016-11-01

    Skin is a multifunctional organ with activities in protection, metabolism and regulation. Skin is in a continuous exposure to oxidizing agents and inflammogens from the sun and from the contact with the environment. These agents may overload the skin auto-defense capacity. To strengthen skin defense mechanisms against oxidation and inflammation, supplementation of exogenous antioxidants is a promising strategy. Quercetin is a flavonoid with very pronounced effective antioxidant and antiinflammatory activities, and thus a candidate of first choice for such skin supplementation. Quercetin showed interesting actions in cellular and animal based models, ranging from protecting cells from UV irradiation to support skin regeneration in wound healing. However, due to its poor solubility, quercetin has limited skin penetration ability, and various formulation approaches were taken to increase its dermal penetration. In this article, the quercetin antioxidant and antiinflammatory activities in wound healing and supporting skin against aging are discussed in detail. In addition, quercetin topical formulations from conventional emulsions to novel nanoformulations in terms of skin penetration enhancement are also presented. This article gives a comprehensive review of quercetin for topical application from biological effects to pharmaceutical formulation design for the last 25 years of research. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Biosorption of Sr(II) from aqueous solutions using aerobic granules. Equilibrium and mechanisms

    Li Wang; Xiang Liu; Xiao-feng Chen; Duu-Jong Lee; Joo-Hwa Tay; Yi Zhang; Chun-li Wan

    2015-01-01

    Aqueous strontium biosorption using aerobic granules was investigated. Parameters affecting the biosorption were optimized, including initial pH, biomass dosage, temperature, and rotation speed. The equilibrium data were fitted using Langmuir and Freundlich models, and both could well describe the process (R 2 = 0.987 and 0.989, respectively). Ion exchange and water-desorption experiments were conducted, and ion exchange together with physical adsorption were found to be the main mechanisms. The aerobic granules were characterized with methods including scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The results showed that surface complexation could also be involved in the Sr(II) biosorption. (author)

  20. Effect of roll compaction on granule size distribution of microcrystalline cellulose–mannitol mixtures: computational intelligence modeling and parametric analysis

    Kazemi P

    2017-01-01

    Full Text Available Pezhman Kazemi,1 Mohammad Hassan Khalid,1 Ana Pérez Gago,2 Peter Kleinebudde,2 Renata Jachowicz,1 Jakub Szlęk,1 Aleksander Mendyk1 1Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland; 2Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany Abstract: Dry granulation using roll compaction is a typical unit operation for producing solid dosage forms in the pharmaceutical industry. Dry granulation is commonly used if the powder mixture is sensitive to heat and moisture and has poor flow properties. The output of roll compaction is compacted ribbons that exhibit different properties based on the adjusted process parameters. These ribbons are then milled into granules and finally compressed into tablets. The properties of the ribbons directly affect the granule size distribution (GSD and the quality of final products; thus, it is imperative to study the effect of roll compaction process parameters on GSD. The understanding of how the roll compactor process parameters and material properties interact with each other will allow accurate control of the process, leading to the implementation of quality by design practices. Computational intelligence (CI methods have a great potential for being used within the scope of quality by design approach. The main objective of this study was to show how the computational intelligence techniques can be useful to predict the GSD by using different process conditions of roll compaction and material properties. Different techniques such as multiple linear regression, artificial neural networks, random forest, Cubist and k-nearest neighbors algorithm assisted by sevenfold cross-validation were used to present generalized models for the prediction of GSD based on roll compaction process setting and material properties. The normalized root-mean-squared error and the coefficient of

  1. Effect of operational strategies on activated sludge’s acclimation to phenol, subsequent aerobic granulation, and accumulation of polyhydoxyalkanoates

    Wosman, Afrida; Lu, Yuhao; Sun, Supu; Liu, Xiang; Wan, Chunli; Zhang, Yi; Lee, Duu-Jong; Tay, JooHwa

    2016-01-01

    Highlights: • Activated sludge was acclimated to phenol with 2 different strategies. • Acclimated sludge later underwent aerobic granulation process. • Sludge acclimated with phenol only degraded phenol and formed granules faster. • Sludge acclimated with phenol + acetate formed more stable and robust granules. • Both sludge exhibited significant PHA accumulation in early granulation stage. - Abstract: Aerobic granules, a relative novel form of microbial aggregate, are capable of degrading many toxic organic pollutants. Appropriate strategy is needed to acclimate seed sludge to the toxic compounds for successful granulation. In this study, two distinct strategies, i.e. mixed or single carbon sources, were experimented to obtain phenol-acclimated sludge. Their effects on reactor performance, biomass characteristics, microbial population and the granulation process were analyzed. Sludge fed with phenol alone exhibited faster acclimation and earlier appearance of granules, but possibly lower microbial diversity and reactor stability. Using a mixture of acetate and phenol in the acclimation stage, on the other hand, led to a reactor with slower phenol degradation and granulation, but eventual formation of strong and stable aerobic granules. In addition, the content of intracellular polyhydoxyakanoates (PHA) was also monitored, and significant accumulation was observed during the pre-granulation stage, where PHA >50% of dry weight was observed in both reactors.

  2. Effect of operational strategies on activated sludge’s acclimation to phenol, subsequent aerobic granulation, and accumulation of polyhydoxyalkanoates

    Wosman, Afrida; Lu, Yuhao; Sun, Supu; Liu, Xiang [Department of Environmental Science and Engineering, Fudan University, 220 Handan Road, Yangpu District, Shanghai, 200433 (China); Wan, Chunli, E-mail: hitwan@163.com [Department of Environmental Science and Engineering, Fudan University, 220 Handan Road, Yangpu District, Shanghai, 200433 (China); Zhang, Yi, E-mail: sybil_zhang@yahoo.com [Department of Environmental Science and Engineering, Fudan University, 220 Handan Road, Yangpu District, Shanghai, 200433 (China); Lee, Duu-Jong [Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan (China); Tay, JooHwa [Department of Civil Engineering, University of Calgary, Calgary, AB T2N 1N4 (Canada)

    2016-11-05

    Highlights: • Activated sludge was acclimated to phenol with 2 different strategies. • Acclimated sludge later underwent aerobic granulation process. • Sludge acclimated with phenol only degraded phenol and formed granules faster. • Sludge acclimated with phenol + acetate formed more stable and robust granules. • Both sludge exhibited significant PHA accumulation in early granulation stage. - Abstract: Aerobic granules, a relative novel form of microbial aggregate, are capable of degrading many toxic organic pollutants. Appropriate strategy is needed to acclimate seed sludge to the toxic compounds for successful granulation. In this study, two distinct strategies, i.e. mixed or single carbon sources, were experimented to obtain phenol-acclimated sludge. Their effects on reactor performance, biomass characteristics, microbial population and the granulation process were analyzed. Sludge fed with phenol alone exhibited faster acclimation and earlier appearance of granules, but possibly lower microbial diversity and reactor stability. Using a mixture of acetate and phenol in the acclimation stage, on the other hand, led to a reactor with slower phenol degradation and granulation, but eventual formation of strong and stable aerobic granules. In addition, the content of intracellular polyhydoxyakanoates (PHA) was also monitored, and significant accumulation was observed during the pre-granulation stage, where PHA >50% of dry weight was observed in both reactors.

  3. Microbial granulation for lactic acid production.

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon; Im, Wan-Taek; Yun, Yeo-Myeong; Park, Chul; Kim, Mi-Sun

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L(-1) d(-1) . As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT. Up to the HRT decrease to 0.5 h, the LA concentration was maintained at 19-20 g L(-1) with over 90% of substrate removal efficiency. However, further decrease of HRT resulted in a decrease of LA concentration with increase in residual glucose. Nevertheless, the volumetric LA productivity continuously increased, reaching 67 g L-fermenter (-1) h(-1) at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s(-1) and 0.39-0.92, respectively. © 2015 Wiley Periodicals, Inc.

  4. Plant RNA Regulatory Network and RNA Granules in Virus Infection

    Kristiina Mäkinen

    2017-12-01

    Full Text Available Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and

  5. Plant RNA Regulatory Network and RNA Granules in Virus Infection.

    Mäkinen, Kristiina; Lõhmus, Andres; Pollari, Maija

    2017-01-01

    Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual

  6. Performance of single carbon granules as perspective for larger scale capacitive bioanodes

    Borsje, Casper; Liu, Dandan; Sleutels, Tom H.J.A.; Buisman, Cees J.N.; Heijne, ter Annemiek

    2016-01-01

    The use of high surface area electrodes, like carbon-based felt or granules, in Bioelectrochemical Systems is crucial for high volumetric current production. In case activated carbon granules are used, charge can also be stored in the form of an electric double layer in the pores, which has been

  7. Calcium phosphate granulation in anaerobic treatment of black water: a new approach to phosphorus recovery

    Tervahauta, T.H.; Weijden, van der R.D.; Flemming, R.L.; Hernández, L.; Zeeman, G.; Buisman, C.J.N.

    2014-01-01

    Recovery of phosphorus from wastewater as calcium phosphate could diminish the need for mining of scarce phosphate rock resources. This study introduces a novel approach to phosphorus recovery by precipitation of calcium phosphate granules in anaerobic treatment of black water. The granules formed

  8. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    Xie Ming

    2012-01-01

    Full Text Available The protective effect of Compound Yangshen Granules was observed in myocardial infarction rat model. Rats were randomly divided into 6 groups: the model group, the control group (sham operated, the positive drug group, and small, medium, and large dosage of the Yangshen granule groups, respectively. The rats in the 3 Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and model groups orally administrated with saline. The rat model of acute myocardial infarction was established with ligation of coronary artery. Electrocardiograms at different time points, the blood rheology, myocardial enzymes, infarct size, and myocardial morphologic changes were measured. The results demonstrated that the granules could improve blood rheology, decrease st-segment of electrocardiograms and the activities of LDH and CK in serum, reduce myocardial infarction size, and alleviate myocardial histopathologic changes. In addition, the effect of the granules depended on the dose administrated orally. The results suggest that the Yangshen granules could produce cardioprotection effect and have potential benefits in the prevention of ischemic heart disease.

  9. Multidimensional modelling of anaerobic granules

    Picioreanu, C.; Batstone, Damien J.; van Loosdrecht, M.C.M.

    2005-01-01

    A multispecies, two- and three-dimensional model was developed, based on a previously published planar biofilm model, and the biochemical structure of the ADM1. Several soluble substrates diffuse and react in the granule. Local pH is calculated from acid-base equilibria and charge balance. The mo...

  10. Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

    Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

    2007-11-01

    Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

  11. Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

    Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

    2018-04-01

    Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

  12. Layered growth with bottom-spray granulation for spray deposition of drug.

    Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

    2009-07-30

    The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

  13. Granulation for Coking Wastewater Treatment in a Coupled Anaerobic-Aerobic Reactor

    Dong, Chunjuan; Lv, Bingnan

    2018-06-01

    A coupled anaerobic-aerobic granular bio-film reactor was employed with two operation stages: Stage I, granular sludge was formed from digestion sludge using brewery wastewater, and Stage II, granular sludge was acclimatized using coking wastewater. Two oxygenation methods (i.e. A and B) were employed to acclimatize the granules. For method A, dissolved O 2 was supplied through a continuous oxygenation way of 800-15000ml-min-1 . And for method B, dissolved O2 was supplied of 800-15000ml-min-1 18-12 times at 20-60min intervals, 1h each time. The experimental results showed that granules could quickly form in 10d in the EGSB reactor seeded with digestion sludge and little loose granules lack of nutrition, and it was the key factor for granules forming to add little loose granules. It took only about 6 months for granules acclimation using coking wastewater. Both oxygenation methods could run well when acclimatizing the granules. However, method A could have comparatively high and stable operation effect. The actual coking wastewater had distinct inhibition effect on the granules, but the supplement of some oxygen could promote the recovery of SMA, and NaHCO3 supplement could also weaken the inhibition effect of the CWW. Method A had more strongly activity recovery ability than method B.

  14. [Pharmacological availability of erythromycin granules for children's use].

    Korenev, S V; Garsheva, G B; Nesterova, L Ia; Grakovskaia, L K; Tentsova, A I

    1990-08-01

    Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied. With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent. The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media. The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug.

  15. UVC-induced stress granules in mammalian cells.

    Mohamed Taha Moutaoufik

    Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

  16. Formation of tRNA granules in the nucleus of heat-induced human cells

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  17. Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process.

    Nozawa, Kenji; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2015-11-10

    To generate products containing a stable form of clarithromycin (CAM) (form II) regardless of the initial crystal form of CAM or type of granulation solvent, the effects of five surfactants, or a water-soluble polymer (macrogol 400) were determined on the crystal transition of CAM. The metastable form (form I) was kneaded with water, after adding surfactants, or a water-soluble polymer. Form II was also kneaded with ethanol, after adding the same additives. The resulting samples were analyzed by powder X-ray diffraction. Form I was completely converted to form II by a wet granulation using water with additives bearing polyoxyethylene chains such as polysorbate 80 (PS80), polyoxyl 40 stearate or macrogol 400. The granulation of the form II using ethanol with these additives did not result in a crystal transition to form I. Furthermore, CAM tablets were manufactured using granules with PS80, and these crystal forms and dissolution behaviors were investigated. As a result, the wet granulation of CAM with PS80 gave CAM tablets containing only form II and PS80 did not have any adverse effects on tablet characteristics. Therefore, these data suggests that the crystal form of CAM can be controlled to be form II using a wet granulation process with additives bearing polyoxyethylene chains regardless of the initial crystal form of CAM or type of granulation solvent. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience

    Cecilia Zampedri

    2016-10-01

    Full Text Available Stress granules are cytoplasmic foci that directly respond to the protein synthesis status of the cell. Various environmental insults, such as oxidative stress or extreme heat, block protein synthesis; consequently, mRNA will stall in translation, and stress granules will immediately form and become enriched with mRNAs. P54 DEAD box RNA helicases are components of RNA granules such as P-bodies and stress granules. We studied the expression, in cytoplasmic foci, of both zebrafish P54 RNA helicases (P54a and P54b during development and found that they are expressed in cytoplasmic granules under both normal conditions and stress conditions. In zebrafish embryos exposed to heat shock, some proportion of P54a and P54b helicases move to larger granules that exhibit the properties of genuine stress granules. Knockdown of P54a and/or P54b in zebrafish embryos produces developmental abnormalities restricted to the posterior trunk; further, these embryos do not form stress granules, and their survival upon exposure to heat-shock conditions is compromised. Our observations fit the model that cells lacking stress granules have no resilience or ability to recover once the stress has ended, indicating that stress granules play an essential role in the way organisms adapt to a changing environment.

  19. The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG

    Hiroshi Takasaki

    2015-01-01

    Full Text Available The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met using the moist aqueous granulation (MAG process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64, polyvidone (Povidone K12: PVP, hydroxypropyl cellulose (HPC SSL SF: HPC and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API. HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance.

  20. Improving the hardness of dry granulated tablets containing sodium lauryl sulfate.

    Moore, Francis; Okelo, Geoffrey; Colón, Ivelisse; Kushner, Joseph

    2010-11-15

    The impact of the addition of a wetting agent, the surfactant sodium lauryl sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form was investigated. In three batches, SLS was added concurrently with: (1) a poorly soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other excipients prior to the initial blending step, (2) magnesium stearate prior to roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch, which did not contain SLS, served as a control. The maximum hardness of 100 mg, 1/4″-SRC tablets for the four batches--SLS added initially, prior to roller compaction, prior to tableting, and no SLS--were 61±3, 71±3, 89±5, and 86±3N, respectively, suggesting reduced processing of SLS improves tablet hardness by ∼50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with paddles at 75 rpm showed that: (1) there was no impact on the insertion point of SLS into the process on API dissolution, and (2) that the presence of SLS improved dissolution by 5% compared to the control tablets. Adding SLS just prior to tableting can improve tablet hardness and yield similar dissolution performance relative to SLS addition prior to the initial blending step. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Effect of particle size of granules on some mechanical properties of ...

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... compacts formed from larger granules as a result of plastic deformation and fragmentation than ... whether an increase or a decrease in particle size will ... many) was used for the preparation of the tablets from the various.

  2. Increased accuracy of starch granule type quantification using mixture distributions

    Tanaka, Emi; Ral, Jean-Phillippe F.; Li, Sean; Gaire, Raj; Cavanagh, Colin R.; Cullis, Brian R.; Whan, Alex

    2017-01-01

    Background The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority...

  3. A Single-Granule-Level Approach Reveals Ecological Heterogeneity in an Upflow Anaerobic Sludge Blanket Reactor.

    Kyohei Kuroda

    Full Text Available Upflow anaerobic sludge blanket (UASB reactor has served as an effective process to treat industrial wastewater such as purified terephthalic acid (PTA wastewater. For optimal UASB performance, balanced ecological interactions between syntrophs, methanogens, and fermenters are critical. However, much of the interactions remain unclear because UASB have been studied at a "macro"-level perspective of the reactor ecosystem. In reality, such reactors are composed of a suite of granules, each forming individual micro-ecosystems treating wastewater. Thus, typical approaches may be oversimplifying the complexity of the microbial ecology and granular development. To identify critical microbial interactions at both macro- and micro- level ecosystem ecology, we perform community and network analyses on 300 PTA-degrading granules from a lab-scale UASB reactor and two full-scale reactors. Based on MiSeq-based 16S rRNA gene sequencing of individual granules, different granule-types co-exist in both full-scale reactors regardless of granule size and reactor sampling depth, suggesting that distinct microbial interactions occur in different granules throughout the reactor. In addition, we identify novel networks of syntrophic metabolic interactions in different granules, perhaps caused by distinct thermodynamic conditions. Moreover, unseen methanogenic relationships (e.g. "Candidatus Aminicenantes" and Methanosaeta are observed in UASB reactors. In total, we discover unexpected microbial interactions in granular micro-ecosystems supporting UASB ecology and treatment through a unique single-granule level approach.

  4. A Single-Granule-Level Approach Reveals Ecological Heterogeneity in an Upflow Anaerobic Sludge Blanket Reactor

    Mei, Ran; Narihiro, Takashi; Bocher, Benjamin T. W.; Yamaguchi, Takashi; Liu, Wen-Tso

    2016-01-01

    Upflow anaerobic sludge blanket (UASB) reactor has served as an effective process to treat industrial wastewater such as purified terephthalic acid (PTA) wastewater. For optimal UASB performance, balanced ecological interactions between syntrophs, methanogens, and fermenters are critical. However, much of the interactions remain unclear because UASB have been studied at a “macro”-level perspective of the reactor ecosystem. In reality, such reactors are composed of a suite of granules, each forming individual micro-ecosystems treating wastewater. Thus, typical approaches may be oversimplifying the complexity of the microbial ecology and granular development. To identify critical microbial interactions at both macro- and micro- level ecosystem ecology, we perform community and network analyses on 300 PTA–degrading granules from a lab-scale UASB reactor and two full-scale reactors. Based on MiSeq-based 16S rRNA gene sequencing of individual granules, different granule-types co-exist in both full-scale reactors regardless of granule size and reactor sampling depth, suggesting that distinct microbial interactions occur in different granules throughout the reactor. In addition, we identify novel networks of syntrophic metabolic interactions in different granules, perhaps caused by distinct thermodynamic conditions. Moreover, unseen methanogenic relationships (e.g. “Candidatus Aminicenantes” and Methanosaeta) are observed in UASB reactors. In total, we discover unexpected microbial interactions in granular micro-ecosystems supporting UASB ecology and treatment through a unique single-granule level approach. PMID:27936088

  5. Polymorphic Transformation of Indomethacin during Hot Melt Extrusion Granulation: Process and Dissolution Control.

    Xu, Ting; Nahar, Kajalajit; Dave, Rutesh; Bates, Simon; Morris, Kenneth

    2018-05-10

    To study and elucidate the effect of the intensity and duration of processing stresses on the possible solid-state changes during a hot melt extrusion granulation process. Blends of α-indomethacin and PEG 3350 (w/w 4:1) were granulated using various screw sizes/designs on the melt extruder under different temperature regimes. Differential Scanning Calorimetry and X-ray Powder Diffraction were employed for characterization. The dissolution behavior of the pure polymorphs and the resulting granules was determined using in-situ fiber optic UV testing system. An XRPD quantitation method using Excel full pattern fitting was developed to determine the concentration of each constituent (amorphous, α and γ indomethacin and PEG) in samples collected from each functioning zone and in granules. Analysis of in-process samples and granules revealed that higher temperature (≥130°C) and shear stress accelerated the process induced phase transitions from amorphous and/or the α form to γ indomethacin during heating stage. However, rapid cooling resulted in an increased percentage of the α form allowing isolation of the meta-stable form. By determining the conditions that either prevent or facilitate process induced transformations of IMC polymorphs during melt granulation, a design space was developed to control the polymorph present in the resulting granules. This represents the conditions necessary to balance the thermodynamic relationships between the polymorphs of the IMC system and the kinetics of the possible transformations as a function of the processing stresses.

  6. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  7. Aspergillus oryzae AoSO is a novel component of stress granules upon heat stress in filamentous fungi.

    Hsiang-Ting Huang

    Full Text Available Stress granules are a type of cytoplasmic messenger ribonucleoprotein (mRNP granule formed in response to the inhibition of translation initiation, which typically occurs when cells are exposed to stress. Stress granules are conserved in eukaryotes; however, in filamentous fungi, including Aspergillus oryzae, stress granules have not yet been defined. For this reason, here we investigated the formation and localization of stress granules in A. oryzae cells exposed to various stresses using an EGFP fusion protein of AoPab1, a homolog of Saccharomyces cerevisiae Pab1p, as a stress granule marker. Localization analysis showed that AoPab1 was evenly distributed throughout the cytoplasm under normal growth conditions, and accumulated as cytoplasmic foci mainly at the hyphal tip in response to stress. AoSO, a homolog of Neurospora crassa SO, which is necessary for hyphal fusion, colocalized with stress granules in cells exposed to heat stress. The formation of cytoplasmic foci of AoSO was blocked by treatment with cycloheximide, a known inhibitor of stress granule formation. Deletion of the Aoso gene had effects on the formation and localization of stress granules in response to heat stress. Our results suggest that AoSO is a novel component of stress granules specific to filamentous fungi. The authors would specially like to thank Hiroyuki Nakano and Kei Saeki for generously providing experimental and insightful opinions.

  8. Determination of methadone hydrochloride in a maintenance dosage formulation.

    Hoffmann, T J; Thompson, R D

    1975-07-01

    A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

  9. Medical image of the week: granulation tissue

    Ganesh A

    2014-03-01

    Full Text Available A 57 year old woman presented with a tickling sensation in the back of throat and intermittent bleeding from the healing stoma one month after decannulation of her tracheostomy tube. On bronchoscopy a granuloma with surrounding granulation tissue was present in the subglottic space (Figure 1. Argon plasma coagulation (APC was performed to cauterize the granulation tissue (Figure 2. Formation of granulation tissue after tracheostomy is a common complication which can result in tracheal stenosis. APC and electrocautery using flexible bronchoscopy has been shown to safely and effectively remove the granulation tissue.

  10. Development of clinical dosage forms for a poorly water-soluble drug II: formulation and characterization of a novel solid microemulsion preconcentrate system for oral delivery of a poorly water-soluble drug.

    Li, Ping; Hynes, Sara R; Haefele, Thomas F; Pudipeddi, Madhu; Royce, Alan E; Serajuddin, Abu T M

    2009-05-01

    The solution of a poorly water-soluble drug in a liquid lipid-surfactant mixture, which served as a microemulsion preconcentrate, was converted into a solid form by incorporating it in a solid polyethylene glycol (PEG) matrix. The solid microemulsion preconcentrates thus formed consisted of Capmul PG8 (propylene glycol monocaprylate) as oil, Cremophor EL (polyoxyl 35 castor oil) as surfactant, and hydrophilic polymer PEG 3350 as solid matrix. The drug (aqueous solubility: 0.17 microg/mL at pH 1-8 and 25 degrees C) was dissolved in a melt of the mixture at 65-70 degrees C and then the hot solution was filled into hard gelatin capsules; the liquid gradually solidified upon cooling below 55 degrees C. The solid system was characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), confocal Raman microscopy (CRM), and the dispersion testing in water. It was confirmed that a solid microemulsion preconcentrate is a two-phase system, where clusters of crystalline PEG 3350 formed the solid structure (m.p. 55-60 degrees C) and the liquid microemulsion preconcentrate dispersed in between PEG 3350 crystals as a separate phase. The drug remained dissolved in the liquid phase. In vitro release testing showed that the preconcentrate dispersed readily in water forming a microemulsion with the drug dissolved in the oil particles (PEG 3350 did not interfere with the process of self-microemulsification.

  11. Distribution of binder in granules produced by means of twin screw granulation

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen

    2014-01-01

    According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding...

  12. The paradox of high shear granulation : the formation of non-homogeneous granules

    Dries, Kaspar van den

    2004-01-01

    Wet granulation is a process used for the particle size enlargement of primary powders. The mixing of a liquid with the powder glues the primary particles together, which results in the formation of the granules. The mixing action can be performed in many ways, like tumbling (drum granulation),

  13. Ocular Injury due to Potassium Permanganate Granules

    Chareenun Chirapapaisan

    2018-02-01

    Full Text Available Purpose: We report a rare case of ocular injury due to potassium permanganate (KMnO4 granules in a child. Methods: This is a retrospective case report. Results: A 2-year-old boy was transferred to our emergency room with severe pain in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical injury was suspected. Copious eye irrigation was immediately performed. Diffuse brownish splotches were then observed at the inferior bulbar conjunctiva. Otherwise, systemic organs were intact. Complete eye exam under general anesthesia revealed a 5-mm epithelial defect at the central cornea, along with generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi-dissolved granules of KMnO4 trapped in the inferior fornix were identified. The chemical particles were gradually washed out and removed; however, the brownish stains remained. The patient received preservative-free steroid, antibiotic eye drops, and lubricants as regular management for mild to moderate degree of ocular burn. Pseudomembrane developed early and transformed into symblepharon within a few days after the injury. Membrane adhesion was lysed, and more aggressive medications were then substituted. Commercial amniotic membrane (PROKERA® was also applied to promote wound healing and to prevent recurrence of symblepharon. The ocular surface was eventually restored, and corneal transparency was preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its toxicity is comparable to concentrated KMnO4 solution. However, the dissolved particles that had been absorbed in the stained conjunctiva were continuously released and damaged the ocular surface more than we primarily anticipated. Awareness of this condition and prompt management yield a good treatment outcome.

  14. Melatonin charge transfer complex with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone: Molecular structure, DFT studies, thermal analyses, evaluation of biological activity and utility for determination of melatonin in pure and dosage forms

    Mohamed, Gehad G.; Hamed, Maher M.; Zaki, Nadia G.; Abdou, Mohamed M.; Mohamed, Marwa El-Badry; Abdallah, Abanoub Mosaad

    2017-07-01

    A simple, accurate and fast spectrophotometric method for the quantitative determination of melatonin (ML) drug in its pure and pharmaceutical forms was developed based on the formation of its charge transfer complex with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an electron acceptor. The different conditions for this method were optimized accurately. The Lambert-Beer's law was found to be valid over the concentration range of 4-100 μg mL- 1 ML. The solid form of the CT complex was structurally characterized by means of different spectral methods. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were carried out. The different quantum chemical parameters of the CT complex were calculated. Thermal properties of the CT complex and its kinetic thermodynamic parameters were studied, as well as its antimicrobial and antifungal activities were investigated. Molecular docking studies were performed to predict the binding modes of the CT complex components towards E. coli bacterial RNA and the receptor of breast cancer mutant oxidoreductase.

  15. Coating of waste containing ceramic granules

    Neumann, W.; Kofler, O.

    1979-01-01

    Simulated high-level waste granules produced by fluidized-bed calcination were overcoated by chemical vapor deposition (CVD) with pyrocarbon and nickel in laboratory-scale experiments. Successful development enables pyrocrbon deposition at temperatures of 600 to 800 0 K. The coated granules have excellent properties for long-term waste storage

  16. Multiphase flow in spout fluidized bed granulators

    Buijtenen, van M.S.

    2011-01-01

    Spout fluidized beds are frequently used for the production of granules or particles through granulation, which are widely applied, for example, in the production of detergents, pharmaceuticals, food and fertilizers (M¨orl et al. 2007). Spout fluidized beds have a number of advantageous properties,

  17. Twin screw wet granulation: Binder delivery.

    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-06-20

    The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV). The binder was delivered in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed with powder mixture and 50% mixed with water, all the solid binder dissolved in water. Incorporation of all solid binder with powder mixture resulted in the relatively longer residence time and higher torque, narrower granule size distribution, more spherical granules, weaker big-sized granules, stronger small-sized granules and better binder distribution compared to that in other two ways. The surface velocity of granules showed variation from one screw to another as a result of uneven liquid distribution as well as shown a reduction while introducing the kneading elements into the screw configuration. Copyright © 2015. Published by Elsevier B.V.

  18. Surface Modification of Porous Titanium Granules for Improving Bioactivity.

    Karaji, Zahra Gorgin; Houshmand, Behzad; Faghihi, Shahab

    The highly porous titanium granules are currently being used as bone substitute material and for bone tissue augmentation. However, they suffer from weak bone bonding ability. The aim of this study was to create a nanostructured surface oxide layer on irregularly shaped titanium granules to improve their bioactivity. This could be achieved using optimized electrochemical anodic oxidation (anodizing) and heat treatment processes. The anodizing process was done in an ethylene glycol-based electrolyte at an optimized condition of 60 V for 3 hours. The anodized granules were subsequently annealed at 450°C for 1 hour. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) were used to characterize the surface structure and morphology of the granules. The in vitro bioactivity of the samples was evaluated by immersion of specimens in simulated body fluid (SBF) for 1, 2, and 3 weeks. The human osteoblastic sarcoma cell line, MG63, was used to evaluate cell viability on the samples using dimethylthiazol-diphenyl tetrazolium bromide (MTT) assay. The results demonstrated the formation of amorphous nanostructured titanium oxide after anodizing, which transformed to crystalline anatase and rutile phases upon heat treatment. After immersion in SBF, spherical aggregates of amorphous calcium phosphate were formed on the surface of the anodized sample, which turned into crystalline hydroxyapatite on the surface of the anodized annealed sample. No cytotoxicity was detected among the samples. It is suggested that anodic oxidation followed by heat treatment could be used as an effective surface treatment procedure to improve bioactivity of titanium granules implemented for bone tissue repair and augmentation.

  19. GRANULATION AND BRIQUETTING OF SOLID PRODUCTS FROM FLUE GAS DESULFURIZATION

    Jan J. Hycnar

    2015-11-01

    Full Text Available Most flue gas desulfurization products can be characterized by significant solubility in water and dusting in dry state. These characteristics can cause a considerable pollution of air, water, and soil. Among many approaches to utilization of this waste, the process of agglomeration using granulation or briquetting has proved very effective. Using desulfurization products a new material of aggregate characteristics has been acquired, and this material is resistant to water and wind erosion as well as to the conditions of transportation and storage. The paper presents the results of industrial trials granulation and briquetting of calcium desulphurization products. The granulation of a mixture of phosphogypsum used with fly ash (in the share 1:5. The resulting granules characterized by a compressive strength of 41.6 MPa, the damping resistance of 70% and 14.2% abrasion. The granulate was used for the production of cement mix. The produced concrete mortar have a longer setting and hardening time, as compared to the traditional ash and gypsum mortar, and have a higher or comparable flexural and compressive strength during hardening. Briquetting trials made of a product called synthetic gypsum or rea-gypsum both in pure form and with the addition of 5% and 10% of the limestone dust. Briquettes have a high initial strength and resistance to abrasion. The values ​​of these parameters increased after 72 hours of seasoning. It was found that higher hardiness of briquettes with rea-gypsum was obtained with the impact of atmospheric conditions and higher resistance to elution of water-soluble components in comparison to ash briquettes.

  20. Spontaneous calcium waves in granule cells in cerebellar slice cultures

    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and es......, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits....

  1. Light scattering on PHA granules protects bacterial cells against the harmful effects of UV radiation.

    Slaninova, Eva; Sedlacek, Petr; Mravec, Filip; Mullerova, Lucie; Samek, Ota; Koller, Martin; Hesko, Ondrej; Kucera, Dan; Marova, Ivana; Obruca, Stanislav

    2018-02-01

    Numerous prokaryotes accumulate polyhydroxyalkanoates (PHA) in the form of intracellular granules. The primary function of PHA is the storage of carbon and energy. Nevertheless, there are numerous reports that the presence of PHA granules in microbial cells enhances their stress resistance and fitness when exposed to various stress factors. In this work, we studied the protective mechanism of PHA granules against UV irradiation employing Cupriavidus necator as a model bacterial strain. The PHA-accumulating wild type strain showed substantially higher UV radiation resistance than the PHA non-accumulating mutant. Furthermore, the differences in UV-Vis radiation interactions with both cell types were studied using various spectroscopic approaches (turbidimetry, absorption spectroscopy, and nephelometry). Our results clearly demonstrate that intracellular PHA granules efficiently scatter UV radiation, which provides a substantial UV-protective effect for bacterial cells and, moreover, decreases the intracellular level of reactive oxygen species in UV-challenged cells. The protective properties of the PHA granules are enhanced by the fact that granules specifically bind to DNA, which in turn provides shield-like protection of DNA as the most UV-sensitive molecule. To conclude, the UV-protective action of PHA granules adds considerable value to their primary storage function, which can be beneficial in numerous environments.

  2. NEDDylation promotes stress granule assembly.

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-07-06

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

  3. Roll Compaction/Dry Granulation of Dibasic Calcium Phosphate Anhydrous-Does the Morphology of the Raw Material Influence the Tabletability of Dry Granules?

    Grote, Simon; Kleinebudde, Peter

    2018-04-01

    The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, 2 agglomerated grades with different porosities, and a functionalized structure, that is, an agglomerate formed by very small primary particles, were included. Particle size, density, and specific surface area of raw materials were measured. The starting materials and 2 fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force, granule size, and lubrication on tablet tensile strength was evaluated. All materials showed a loss in tabletability induced by a previous compaction step but to a varying extent. Only in case of the functionalized calcium phosphate morphology, this effect depended on the specific compaction force. In contrast to the other materials, the tabletability of functionalized calcium phosphate was influenced by the granule size. This effect was not related to an overlubrication as internal and external lubrication resulted in similar tensile strengths. A clear influence of the particle morphology on tablet strength was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. The functionalized dibasic calcium phosphate and the more porous agglomerate performed as potential filler/binder in the field of roll compaction/dry granulation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor

    Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

    2015-08-01

    Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3--N could be removed or reduced, some amount of NO2--N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy.

  5. Dissipation and residue of clothianidin in granules and pesticide fertilizers used in cabbage and soil under field conditions.

    Zhang, P W; Wang, S Y; Huang, C L; Fu, J T; Huang, R L; Li, Z H; Zhang, Z X

    2018-01-01

    The single application of 0.5 % clothianidin granules, a novel formulation, was used to control pests in vegetables under a high dose. In this article, residues of clothianidin in cabbage and soil samples under field conditions from Guangzhou, Nanning, and Qianjiang were determined by HPLC. The terminal residues of clothianidin in cabbage were less than the limit of detection (clothianidin residual, clothianidin granules and fertilizers of chicken manure, urea, and organic fertilizer were mixed into different pesticide fertilizers through their normal field using dosage and evaluate residual influence of clothianidin in different formula. After analysis of variance of the effect factors, the effect of different pesticide types on half-life was not significant, but the effect of sample types was significant. Clothianidin granules and pesticide fertilizers could be safely applied in cabbage under a single high-dose administration.

  6. Dosage of trace carbon in sodium (1963); Dosage de traces de carbone dans le sodium (1963)

    Sannier, J; Vasseur, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    A wet method for dosing carbon in sodium has been developed. The carbon is oxidised in a vacuum using Van SLYKE'S solution. The carbonic acid formed is measured volumetrically; its purity can be controlled by chromatographic analysis. The results obtained show that this method makes it possible to measure carbon in concentrations of about 10 ppm. (authors) [French] Une methode de dosage par voie humide du carbone dans le sodium a ete mise au point. L'oxydation du carbone par la solution de Van SLYKE est realisee sous vide. Le gaz carbonique forme est dose volumetriquement; sa purete peut etre controlee par analyse chromatographique. Les resultats obtenus montrent que cette methode permet de doser des teneurs en carbone de l'ordre de 10 ppm. (auteurs)

  7. Hydraulic Modular Dosaging Systems for Machine Drives

    A. J. Kotlobai

    2005-01-01

    Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

  8. Study on acute toxicity of anti-vertigo granule on mice

    Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

    2018-04-01

    To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

  9. Polyhydroxyalkanoate (PHA) Granules Have no Phospholipids

    Bresan, Stephanie; Sznajder, Anna; Hauf, Waldemar; Forchhammer, Karl; Pfeiffer, Daniel; Jendrossek, Dieter

    2016-01-01

    Polyhydroxybutyrate (PHB) granules, also designated as carbonosomes, are supra-molecular complexes in prokaryotes consisting of a PHB polymer core and a surface layer of structural and functional proteins. The presence of suspected phospholipids in the surface layer is based on in vitro data of isolated PHB granules and is often shown in cartoons of the PHB granule structure in reviews on PHB metabolism. However, the in vivo presence of a phospholipid layer has never been demonstrated. We addressed this topic by the expression of fusion proteins of DsRed2EC and other fluorescent proteins with the phospholipid-binding domain (LactC2) of lactadherin in three model organisms. The fusion proteins specifically localized at the cell membrane of Ralstonia eutropha but did not co-localize with PHB granules. The same result was obtained for Pseudomonas putida, a species that accumulates another type of polyhydroxyalkanoate (PHA) granules related to PHB. Notably, DsRed2EC-LactC2 expressed in Magnetospirillum gryphiswaldense was detected at the position of membrane-enclosed magnetosome chains and at the cytoplasmic membrane but not at PHB granules. In conclusion, the carbonosomes of representatives of α-proteobacteria, β-proteobacteria and γ-proteobacteria have no phospholipids in vivo and we postulate that the PHB/PHA granule surface layers in natural producers generally are free of phospholipids and consist of proteins only. PMID:27222167

  10. Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

    Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth

    2009-01-01

    Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... is the major intracellular proteoglycan of haematopoietic cells. Serglycin is important for localization of proteins in granules of different haematopoietic cell types. Previous reports have indicated a role for serglycin in granule formation and localization of zymogens in granules of the exocrine pancreas...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

  11. Toward quality assessment of 3D printed oral dosage forms

    Markl, Daniel; Zeitler, Axel; Rades, Thomas

    2017-01-01

    The additive manufacturing industry achieved a corporate annual growth rate of 25.9% according to the Forbes analysis of the Wohlers Report 2016. This high growth rate is placed in perspective when looking at the past 27 years where the corporate annual growth rate has averaged 26.2% each year in...... methods to assess the quality of the 3D printed geometries. This will be especially important for pharmaceutical products where a sub-standard quality of the final product can have detrimental consequences for patient health and safety....

  12. Development and clinical application of oral dosage forms of taxanes

    Moes, J.J.

    2013-01-01

    Cancer is still one of the leading causes of death in the Western World. Despite the development and introduction of new anti-cancer agents, docetaxel and paclitaxel remain the cornerstone of adjuvant and metastatic chemotherapy against solid tumors. Taxanes belong to the class of anti-mitotic

  13. Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

    Erah

    Purpose: To develop simple, rapid and selective spectrophotometric methods for ... Conclusion: These validated methods may be useful for routine analysis of cilostazol ... Keywords: Cilostazol tablets, UV spectrophotometry, Linear regression ...

  14. Near infrared spectroscopy in the development of solid dosage forms.

    Räsänen, Eetu; Sandler, Niklas

    2007-02-01

    The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field.

  15. Kinetic spectrophotometric determination of ethamsylate in dosage forms.

    El-Enany, Nahed; Belal, Fathalla; Rizk, Mohamed

    2007-01-01

    A simple and sensitive kinetic method has been developed for the determination of ethamsylate (ESL) in its pharmaceutical preparations. The method is based upon oxidation of ESL with 3-methyl-2-benzothiazolinone hydrazone hydrochloride in presence of cerium (IV) ammonium sulfate at room temperature for 20 min. The absorbance of the reaction product is measured at 514 nm. The absorbance-concentration plot was rectilinear over the range of 4-30 microg/mL (r = 0.9999). The lower detection limit was 0.267 microl/mL (9.110 x 10(-6) M) and the lower quantitation limit was 0.808 microg/mL. The different experimental parameters affecting the development and stability of the reaction product were studied and optimized. The proposed method was applied to the determination of ESL in formulations, and the results obtained were in good agreement with those obtained using a reference method. The proposed method was also used for the in vitro detection of ESL in spiked human plasma at its therapeutic concentration level.

  16. Spectrophotometeric determination of metoprolol in tablet dosage form

    Metoprolol, a beta-1 selective adrenegic receptor blocker antihypertensive agent is fairly new in Nigeria. In view of the endemic faking and adulterating of drugs in Nigeria, a simple, quick, and accurate method was developed for its assay. Metoprolol was coupled with 4-chloro-7-nitrobenzo-2-oxa-1, 3 diazole (NBD-Cl) in ...

  17. 75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

    2010-09-08

    ... certain bacterial respiratory and enteric diseases in swine. The supplemental NADA provides for use of a... Health US, Inc. The supplemental NADA provides for use of an increased strength of tiamulin concentrate solution in the drinking water of swine for the treatment of certain bacterial respiratory and enteric...

  18. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

    Albed Alhnan, Mohamed; Okwuosa, Tochukwu; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-01-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet...

  19. The rationale of scored tablets as dosage form.

    Rodenhuis, N.; Smet, P.A.G.M. de; Barends, D.M.

    2004-01-01

    The aim of the study was to get insight into the rationale of scored tablets. This was pursued by studying patient's reasons for subdividing ("breaking") scored and unscored tablets. Patients who picked up their prescriptions in 5 community pharmacies in The Netherlands were questioned. Two-hundred

  20. quality evaluation of paracetamol in the bulk, dosage forms

    Prince Acheampong

    assay of paracetamol-codeine combination drug as well as estimation of the amount of ... post-market is very essential in the policy and technical guidelines of drug regulatory authorities such as the Food and Drugs Board. ... Pharmaceutical industries may also have simple analytical procedures for both in-process and.

  1. Microbial quality of some herbal solid dosage forms | Enayatifard ...

    Herbal remedies are widely used for the treatment and prevention of various diseases and often contain highly active pharmacological compounds. These products have the potential of contamination with different microorganisms. This is due to raw materials contamination and unhygienic production conditions.

  2. Ocular Insert: Dosage Form for Sustain Opthalmic Drug Delivery

    Sunil Kumar

    2012-06-01

    Full Text Available Except for skin, the eye is the most easily accessible site for topical administration of a medication. Traditional topical ophthalmic formulations (eye drops and ointments have poor bioavailability because of rapid pre-corneal elimination, conjunctival absorption, solution drainage by gravity, induced lacrimation and normal tear turnover. This leads to frequent installations of concentrated medication to achieve a therapeutic effect. The typical “pulse-entry” type drug release observed with ocular aqueous solutions (eye drops, suspensions and ointments can be replaced by more controlled, sustained, and continuous drug delivery, using a controlled-release ocular drug delivery system. Ocular inserts are solid or semisolid sterile preparations, of appropriate size and shape, designed to be inserted behind the eyelid or held on the eye and to deliver drugs for topical or systemic effect. These are polymeric systems into which the drug is incorporated as a solution or dispersion. They are better tolerated as to drainage and tear flow compared with other ophthalmic formulation and produce reliable drug release in the conjunctival cul-de-sac.

  3. 77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

    2012-03-19

    ... Laboratories, Inc. The NADA provides for the veterinary prescription use of phenylpropanolamine hydrochloride... Veterinary Medicine (HFV-116), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276... Ely Rd., Pensacola, FL 32514, filed NADA 141-324 that provides for the veterinary prescription use of...

  4. 76 FR 78815 - Oral Dosage Form New Animal Drugs; Cyclosporine

    2011-12-20

    ..., Inc. The NADA provides for the veterinary prescription use of cyclosporine oral solution, USP.... FOR FURTHER INFORMATION CONTACT: Angela K.S. Clarke, Center for Veterinary Medicine (HFV-112), Food... (cyclosporine oral solution, USP (MODIFIED)) by veterinary prescription for the control of feline allergic...

  5. Morphological study of the solar granulation. Pt. 2

    Kawaguchi, I.

    1980-01-01

    A time sequence of granulation images of 46 min long has allowed us to make a detailed study of the evolution of granules in an area of approximately 17 x 17 on the solar surface; It is found that the granules evolve by repeated fragmentation into smaller granules or merging with adjacent ones and that there are few granules which appear in the intergranular lanes as new granules (Table III). The statistical nature of granules is as follows: (1) A family of granules is defined as a group of granules produced from a single granule by fragmentation or merging. The lifetime is estimated for single granules and for families of granules. The lifetime shows a close correlation with the maximum size of a single granule or with that of the largest granule belonging to a family (Figures 5 and 7). (2) The smaller the size, the more probably a granule will disappear without further fragmentation or merging. The granule whose size is larger than 2 will certainly split or merge as the next evolutional step (Table IV.). (orig.)

  6. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... morphometry and function. Eliane Florencio ... granules is greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. ... family: Atrial natriuretic peptide (ANP), Urodilatin, Brain natriuretic ...

  7. Actinomyces associated with persistent vaginal granulation tissue.

    Wai, Clifford Y; Nihira, Mikio A; Drewes, Peter G; Chang, Joe S; Siddiqui, Momin T; Hemsell, David L

    2005-01-01

    BACKGROUND: We report a case of symptomatic actinomycosis associated with vaginal suture erosion and granulation tissue refractory to conservative management, in an outpatient setting. CASE: Three months after total vaginal hysterectomy and uterosacral ligament vaginal vault suspension, a woman complained of painless, intermittent vaginal discharge and spotting. Despite cauterization of granulation tissue, vaginal spotting persisted for another month. On re-examination, braided polyester sutu...

  8. Mathematical model of melt flow channel granulator

    A. A. Kiselev

    2016-01-01

    Full Text Available Granulation of carbohydrate-vitamin-mineral supplements based on molasses is performed at a high humidity (26 %, so for a stable operation of granulator it is necessary to reveal its melt flow pattern. To describe melt non-isothermal flow in the granulator a mathematical model with following initial equations: continuity equation, motion equation and rheological equation – was developed. The following assumptions were adopted: the melt flow in the granulator is a steady laminar flow; inertial and gravity forces can be ignored; melt is an incompressible fluid; velocity gradient in the flow direction is much smaller than in the transverse direction; the pressure gradient over the cross section of the channel is constant; the flow is hydrodynamically fully developed; effects impact on the channel inlet and outlet may be neglected. Due to the assumptions adopted, it can be considered that in this granulator only velocity components in the x-direction are significant and all the members of the equation with the components and their derivatives with respect to the coordinates y and z can be neglected. The resulting solutions were obtained: the equation for the mean velocity, the equation for determining the volume flow, the formula for calculating of mean time of the melt being in the granulator, the equation for determining the shear stress, the equation for determining the shear rate and the equation for determining the pressure loss. The results of calculations of the equations obtained are in complete agreement with the experimental data; deviation range is 16–19 %. The findings about the melt movement pattern in granulator allowed developing a methodology for calculating a rational design of the granulator molding unit.

  9. Preliminary Research on Granulation Process of Dust Waste from Reclamation Process of Moulding Sands with Furan Resin

    J. Kamińska

    2012-09-01

    Full Text Available The results of investigations of the granulation process of foundry dusts generated in the dry mechanical reclamation process of usedsands, where furan resins were binders are presented in the paper. Investigations concerned producing of granules of the determineddimensions and strength parameters.Granules were formed from the dusts mixture consisting in 50 mass% of dusts obtained after the reclamation of the furane sands and in50 mass % of dusts from sands with bentonite. Dusts from the bentonite sands with water were used as a binder allowing the granulation of after reclamation dusts from the furane sands.The following parameters of the ready final product were determined: moisture content (W, shatter test of granules (Wz performeddirectly after the granulation process and after 1, 3, 5, 10 days and nights of seasoning, water-resistance of granules after 24 hours of being immersed in water, surface porosity ep and volumetric porosity ev. In addition the shatter test and water-resistance of granulate dried at a temperature of 105oC were determined.Investigations were performed at the bowl angle of inclination 45o, for three rotational speeds of the bowl being: 10, 15, 20 rpm.For the speed of 10 rpm the granulation tests of dusts mixture after the preliminary mixing in the roller mixer and with the addition ofwater-glass in the amount of 2% in relation to the amount of dust were carried out.The obtained results indicate that the granulator allows to obtain granules from dusts originated from the reclamations of mouldingsands with the furane resin with an addition of dusts from the bentonite sands processing plants.

  10. Does Thermal Granulation Drive Tephra Jets?

    White, J. D.; Zimanowski, B.; Buettner, R.; Sonder, I.; Dellino, P.

    2011-12-01

    Surtseyan tephra jets, also called cypressoid or cock's tail plumes, comprise a characteristic mixture of ash with bombs travelling roughly ballistic paths that tip the individual fingers of the projecting jet. Jets of similar form but smaller scale are generated by littoral magma-water interactions, confirming the general inference that surtseyan tephra jets are a characteristic product of explosive magma-water interaction, and suggesting that magmatic volatiles play a subsidiary role, if any, in their formation. Surtseyan jets have been inferred to result from both intense fuel-coolant interactions, and from simple boiling of water entrained into rising magma, and little new information has become available to test these two positions since they were clearly developed in the 1980s. Recent experiments in which magma is poured into standing water have produced vigorous jetting of hot water as melt solidifies and undergoes extensive thermal granulation. We present high-resolution hi-speed video of these jets, which we see as having the following origin. As thermal granulation takes place, a fracture network advances into the melt/glass body, and water invading the cracks at the rate of propagation is heated nearly instantaneously. Vapor produced at the contact expands and drives outward through cooled cracks, condensing as it moves to the exterior of the magma body where it is emitted as a jet of hot water. In ocean ridge hydrothermal systems a diffuse crack network inducts cold water, which is heated and expelled in focused jets. Focusing of hot outflow in experiments is inferred to result, as suggested for ridge hydrothermal systems, from thermoelastic closure of cracks near the one(s) feeding the jet. From the cooled products of our experimental runs, we know that thermal contraction produces a network of curved cracks with modal spacing of 1-2 mm, which separate domains of unbroken glass. It is during growth of this crack network that cold water enters, is

  11. Kit systems for granulated decontamination formulations

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  12. Recreating the synthesis of starch granules in yeast

    Pfister, Barbara; Sánchez-Ferrer, Antoni; Diaz, Ana; Lu, Kuanjen; Otto, Caroline; Holler, Mirko; Shaik, Farooque Razvi; Meier, Florence; Mezzenga, Raffaele; Zeeman, Samuel C

    2016-01-01

    Starch, as the major nutritional component of our staple crops and a feedstock for industry, is a vital plant product. It is composed of glucose polymers that form massive semi-crystalline granules. Its precise structure and composition determine its functionality and thus applications; however, there is no versatile model system allowing the relationships between the biosynthetic apparatus, glucan structure and properties to be explored. Here, we expressed the core Arabidopsis starch-biosynthesis pathway in Saccharomyces cerevisiae purged of its endogenous glycogen-metabolic enzymes. Systematic variation of the set of biosynthetic enzymes illustrated how each affects glucan structure and solubility. Expression of the complete set resulted in dense, insoluble granules with a starch-like semi-crystalline organization, demonstrating that this system indeed simulates starch biosynthesis. Thus, the yeast system has the potential to accelerate starch research and help create a holistic understanding of starch granule biosynthesis, providing a basis for the targeted biotechnological improvement of crops. DOI: http://dx.doi.org/10.7554/eLife.15552.001 PMID:27871361

  13. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages

    Jena, Prajna; Mohanty, Soumitra; Mohanty, Tirthankar

    2012-01-01

    Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil...... and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule...... proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane...

  14. TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2+

    Joseph B. Rayman

    2018-01-01

    Full Text Available Summary: Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity. A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1. Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN. Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN. In addition, Zn2+ is released in cells treated with arsenite, before stress granule formation. These findings suggest that Zn2+ is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules. : Rayman et al. show that Zn2+ is a stress-inducible second messenger that triggers self-multimerization and phase separation of TIA-1 and regulates dynamic recruitment of TIA-1 into stress granules. This mechanism is part of an adaptive cellular response to environmental adversity. Keywords: TIA-1, TIA1, stress granules, cellular stress, functional prion, phase separation, zinc regulation

  15. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Somanath, Sangeeta [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Partridge, Christopher J. [Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Churchill Hospital, University of Oxford, Oxford, OX3 7LJ (United Kingdom); Marshall, Catriona [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Rowe, Tony [CSL Limited, 45 Poplar Road, Parkville, Victoria 3052 (Australia); Turner, Mark D., E-mail: mark.turner@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS (United Kingdom)

    2016-04-29

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  16. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Somanath, Sangeeta; Partridge, Christopher J.; Marshall, Catriona; Rowe, Tony; Turner, Mark D.

    2016-01-01

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  17. Aerobic granulation strategy for bioaugmentation of a sequencing batch reactor (SBR) treating high strength pyridine wastewater

    Liu, Xiaodong; Chen, Yan [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China); Zhang, Xin [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China); Suzhou Institute of Architectural Design Co., Ltd, Suzhou 215021, Jiangsu Province (China); Jiang, Xinbai; Wu, Shijing [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China); Shen, Jinyou, E-mail: shenjinyou@mail.njust.edu.cn [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China); Sun, Xiuyun; Li, Jiansheng; Lu, Lude [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China); Wang, Lianjun, E-mail: wanglj@mail.njust.edu.cn [Jiangsu Key Laboratory for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu Province (China)

    2015-09-15

    Abstract: Aerobic granules were successfully cultivated in a sequencing batch reactor (SBR), using a single bacterial strain Rhizobium sp. NJUST18 as the inoculum. NJUST18 presented as both a good pyridine degrader and an efficient autoaggregator. Stable granules with diameter of 0.5–1 mm, sludge volume index of 25.6 ± 3.6 mL g{sup −1} and settling velocity of 37.2 ± 2.7 m h{sup −1}, were formed in SBR following 120-day cultivation. These granules exhibited excellent pyridine degradation performance, with maximum volumetric degradation rate (V{sub max}) varied between 1164.5 mg L{sup −1} h{sup −1} and 1867.4 mg L{sup −1} h{sup −1}. High-throughput sequencing analysis exhibited a large shift in microbial community structure, since the SBR was operated under open condition. Paracoccus and Comamonas were found to be the most predominant species in the aerobic granule system after the system had stabilized. The initially inoculated Rhizobium sp. lost its dominance during aerobic granulation. However, the inoculation of Rhizobium sp. played a key role in the start-up process of this bioaugmentation system. This study demonstrated that, in addition to the hydraulic selection pressure during settling and effluent discharge, the selection of aggregating bacterial inocula is equally important for the formation of the aerobic granule.

  18. Aerobic granulation strategy for bioaugmentation of a sequencing batch reactor (SBR) treating high strength pyridine wastewater

    Liu, Xiaodong; Chen, Yan; Zhang, Xin; Jiang, Xinbai; Wu, Shijing; Shen, Jinyou; Sun, Xiuyun; Li, Jiansheng; Lu, Lude; Wang, Lianjun

    2015-01-01

    Abstract: Aerobic granules were successfully cultivated in a sequencing batch reactor (SBR), using a single bacterial strain Rhizobium sp. NJUST18 as the inoculum. NJUST18 presented as both a good pyridine degrader and an efficient autoaggregator. Stable granules with diameter of 0.5–1 mm, sludge volume index of 25.6 ± 3.6 mL g −1 and settling velocity of 37.2 ± 2.7 m h −1 , were formed in SBR following 120-day cultivation. These granules exhibited excellent pyridine degradation performance, with maximum volumetric degradation rate (V max ) varied between 1164.5 mg L −1 h −1 and 1867.4 mg L −1 h −1 . High-throughput sequencing analysis exhibited a large shift in microbial community structure, since the SBR was operated under open condition. Paracoccus and Comamonas were found to be the most predominant species in the aerobic granule system after the system had stabilized. The initially inoculated Rhizobium sp. lost its dominance during aerobic granulation. However, the inoculation of Rhizobium sp. played a key role in the start-up process of this bioaugmentation system. This study demonstrated that, in addition to the hydraulic selection pressure during settling and effluent discharge, the selection of aggregating bacterial inocula is equally important for the formation of the aerobic granule

  19. Morphological Characterization of Photosynthetic Microbial Granule from Palm Oil Mill Effluent (POME)

    Najib, M.Z.M.

    2013-01-01

    Presently, global warming is the most highlighted subjects in the environmental issues which relates closely to greenhouse gases (GHG) emissions. In 2007, the Intergovernmental Panel on Climate Change (IPCC) assigns only methane (CH 4 ) emissions to wastewater treatment rather than GHG emissions specifically carbon dioxide (CO 2 ) gas from the aerobic treatment processes. Focusing on the palm oil industry in Malaysia, the most commonly used treatment of palm oil mill effluent (POME) which is the conventional pounding system, has caused excessive generation of GHG such as CH 4 and CO 2 gases. To develop a novel, innovative and environmental-friendly mitigation method, this study explores into the possibility of growing the photosynthetic bacteria in the form of granules via the aerobic granulation process with potential applications in reducing CO 2 gases. The cultivation of photosynthetic microbial granules was investigated using POME as the substrate in a sequencing batch reactor (SBR) system via the sequencing cycle of feeding, reacting, settling and decanting. Evidence of the formation of granule was based on microscopic examination of the morphological changes during the development of the granule in the SBR system over a period of 90 days. It shows changes from dispersed loose structure of the sludge merging into small flocs of irregular shapes and finally into dense and compact granular form. The granule was formed by applying an organic loading rate (OLR) at 2.75 kg COD/ m 3 .day, hydraulic retention time (HRT) at 4 h and superficial air velocity of 2.07 cm/ s. The biomass concentration began to decreased first (initial sludge biomass = 16750 mg/ L) and then increased steadily to a constant value of 32000 mg/ L after 90 days. Besides, the results also demonstrated a good accumulation of biomass as the settleability between raw sludge and granule increased from 0.03 cm/ s to 0.94 cm/ s. The maximum settling velocity obtained in the reactor was approximately 2

  20. Granule size control and targeting in pulsed spray fluid bed granulation.

    Ehlers, Henrik; Liu, Anchang; Räikkönen, Heikki; Hatara, Juha; Antikainen, Osmo; Airaksinen, Sari; Heinämäki, Jyrki; Lou, Honxiang; Yliruusi, Jouko

    2009-07-30

    The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period. The study was performed with a laboratory-scale top-spray fluid bed granulator with duty cycle length and atomization pressure as studied variables. The liquid feed rate, amount and inlet air temperature were constant. The granules were small, indicating that the powder has only undergone ordered mixing, nucleation and early growth. The effect of atomizing pressure on granule size depends on inlet air relative humidity, with premature binder evaporation as a reason. The duty cycle length was of critical importance to the end product attributes, by defining the extent of intermittent drying and rewetting. By varying only the duty cycle length, it was possible to control granule nucleation and growth, with a wider granule size target range in increased relative humidity. The present study confirms that pulsed liquid feed in fluid bed granulation is a useful tool in end product particle size targeting.

  1. Study of light scattering by a granulated coated sphere - a model of granulated blood cells

    Yurkin, M.A.; de Kanter, D.; Hoekstra, A.G.

    2008-01-01

    We performed extensive simulations of light scattering by granulated coated sphere model using the discrete dipole approximation and varying model parameters in the ranges of sizes and refractive indices of granulated blood cells. We compared these results with predictions of Maxwell-Garnett

  2. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

  3. Strategy to identify the causes and to solve a sludge granulation problem in methanogenic reactors: application to a full-scale plant treating cheese wastewater.

    Macarie, Hervé; Esquivel, Maricela; Laguna, Acela; Baron, Olivier; El Mamouni, Rachid; Guiot, Serge R; Monroy, Oscar

    2017-08-26

    Granulation of biomass is at the basis of the operation of the most successful anaerobic systems (UASB, EGSB and IC reactors) applied worldwide for wastewater treatment. Despite of decades of studies of the biomass granulation process, it is still not fully understood and controlled. "Degranulation/lack of granulation" is a problem that occurs sometimes in anaerobic systems resulting often in heavy loss of biomass and poor treatment efficiencies or even complete reactor failure. Such a problem occurred in Mexico in two full-scale UASB reactors treating cheese wastewater. A close follow-up of the plant was performed to try to identify the factors responsible for the phenomenon. Basically, the list of possible causes to a granulation problem that were investigated can be classified amongst nutritional, i.e. related to wastewater composition (e.g. deficiency or excess of macronutrients or micronutrients, too high COD proportion due to proteins or volatile fatty acids, high ammonium, sulphate or fat concentrations), operational (excessive loading rate, sub- or over-optimal water upflow velocity) and structural (poor hydraulic design of the plant). Despite of an intensive search, the causes of the granulation problems could not be identified. The present case remains however an example of the strategy that must be followed to identify these causes and could be used as a guide for plant operators or consultants who are confronted with a similar situation independently of the type of wastewater. According to a large literature based on successful experiments at lab scale, an attempt to artificially granulate the industrial reactor biomass through the dosage of a cationic polymer was also tested but equally failed. Instead of promoting granulation, the dosage caused a heavy sludge flotation. This shows that the scaling of such a procedure from lab to real scale cannot be advised right away unless its operability at such a scale can be demonstrated.

  4. A Survey of Sludge Granulation Theories Under Anaerobic Conditions

    Jalal Shayegan

    2011-01-01

    Full Text Available This paper surveys the different theories developed on anaerobic sludge granulation. The theories are generally categorized as physical, microbial, and thermodynamic approaches. In the physical approach to the granulation process, granulation is described by such physical conditions of the reactor as upflow velocity of gas and liquid streams, suspended solids in the effluent flow, and excess sludge removal. Microbial theories are based on the properties of specific organisms and on granule properties (granule structure and its microbiology. The thermodynamic approach studies such factors as hydrophobia, electrophoretic mobility, effective energy in granule adhesion process, and effect of proton transferring activities on bacterial membrane surfaces.

  5. Antimicrobial-Coated Granules for Disinfecting Water

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  6. Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions

    Nakamura, Hideki; Lee, Albert A.; Afshar, Ali Sobhi; Watanabe, Shigeki; Rho, Elmer; Razavi, Shiva; Suarez, Allister; Lin, Yu-Chun; Tanigawa, Makoto; Huang, Brian; Derose, Robert; Bobb, Diana; Hong, William; Gabelli, Sandra B.; Goutsias, John; Inoue, Takanari

    2018-01-01

    Some protein components of intracellular non-membrane-bound entities, such as RNA granules, are known to form hydrogels in vitro. The physico-chemical properties and functional role of these intracellular hydrogels are difficult to study, primarily due to technical challenges in probing these materials in situ. Here, we present iPOLYMER, a strategy for a rapid induction of protein-based hydrogels inside living cells that explores the chemically inducible dimerization paradigm. Biochemical and biophysical characterizations aided by computational modelling show that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that acts as a size-dependent molecular sieve. We functionalize these polymers with RNA-binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. These results show that iPOLYMER can be used to synthetically reconstitute the nucleation of biologically functional entities, including RNA granules in intact cells.

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

    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 ...

  8. Lemongrass Oil Granules AS Aedes Aegypti Larvicide

    Mulyani, Sri

    2014-01-01

    One way to prevent the spread of Haemorrhage Dengue Fever is the use of abate. The use of abate as larvicides often complained causing an unpleasant smell, and can cause resistance. Lemongrass oil is reported to have activity as larvicides, and this study aims to make granules of lemongrass oil preparation, as well as determining the value of LC50, LC90 against larvae of Ae. aegypti instar III. The granules of lemongrass oil preparation are made with lactose filler and binder CMC-Na. Larvicid...

  9. Method of producing granulated ceramic nuclear fuels

    Wilkinson, W.L.

    1976-01-01

    For the production of granulated ceramic nuclear fuels with a grain size spectrum as narrow as possible it is proposed to suspend the nuclear fuel powder in a non-aqueous solvent with small content of hydrogen (e.g. chloridized hydrocarbons) while adding a binding agent and then dry it by means of rays. As binding agent polybutyl methane acrylate in dibutyl phthalate is proposed. The method is described by the example of UO 2 -powder in trichloroethylene. The dry granulated material is produced in one working step. (UWI) [de

  10. Arachnoid granulation affected by subarachnoid hemorrhage

    R.P. Chopard

    1993-11-01

    Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

  11. Creep of granulated loose-fill insulation

    Rasmussen, Torben Valdbjørn

    This report presents a proposal for a standardised method for creep tests and the necessary theoretical framework that can be used to describe creep of a granulated loose-fill material. Furthermore results from a round robin test are shown. The round robin test was carried out in collaboration...... with SP-Building Physics in Sweden and VTT Building Technology in Finland. For the round robin test a cellulosic fibre insulation material was used. The proposed standardised method for creep tests and theories are limited to cases when the granulated loose-fill material is exposed to a constant...

  12. Molecular composition of IMP1 ribonucleoprotein granules

    Jønson, Lars; Vikesaa, Jonas; Krogh, Anders

    2007-01-01

    Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in mo......Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization...

  13. beta. -Amyloid gene dosage in Alzheimer's disease

    Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

    1988-01-11

    The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

  14. Vaccine adjuvants: Tailor-made mast-cell granules

    Gunzer, Matthias

    2012-03-01

    Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

  15. Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer.

    De Leersnyder, F; Vanhoorne, V; Bekaert, H; Vercruysse, J; Ghijs, M; Bostijn, N; Verstraeten, M; Cappuyns, P; Van Assche, I; Vander Heyden, Y; Ziemons, E; Remon, J P; Nopens, I; Vervaet, C; De Beer, T

    2018-03-30

    Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and, hence, a cost-effective practical implementation. Therefore, the aim of the current study is to increase understanding of the drying kinetics and the breakage and attrition phenomena during fluid bed drying after continuous twin screw granulation. Experiments were performed on a continuous manufacturing line consisting of a twin-screw granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a tablet press. Granulation parameters were fixed in order to only examine the effect of drying parameters (filling time, drying time, air flow, drying air temperature) on the size distribution and moisture content of granules (both of the entire granulate and of size fractions). The wet granules were transferred either gravimetrically or pneumatically from the granulator exit to the fluid bed dryer. After a certain drying time, the moisture content reached an equilibrium. This drying time was found to depend on the applied airflow, drying air temperature and filling time. The moisture content of the granules decreased with an increasing drying time, airflow and drying temperature. Although smaller granules dried faster, the multimodal particle size distribution of the granules did not compromise uniform drying of the granules when the target moisture content was achieved. Extensive breakage of granules was observed during drying. Especially wet granules were prone to breakage and attrition during pneumatic transport, either in the wet transfer line or in the dry transfer line. Breakage and attrition of granules during transport and drying should be anticipated early on during process and formulation development by performing integrated experiments on the granulator

  16. Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation

    Aguilera-Gomez, Angelica; Zacharogianni, Margarita; van Oorschot, Marinke M; Genau, Heide; Grond, Rianne; Veenendaal, Tineke; Sinsimer, Kristina S; Gavis, Elizabeth R; Behrends, Christian; Rabouille, Catherine

    2017-01-01

    Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and sta...

  17. Sodium phenylbutyrate coated granules (Pheburane). Defective urea synthesis: a welcome formulation.

    2015-02-01

    Compared with Ammonaps granules, Pheburane coated granules mask the unpleasant taste of sodium phenylbutyrate. A more precise dosing device is provided with the coated granules than with the uncoated granules (Ammonaps).

  18. Detection and Analysis of the Quality of Ibuprofen Granules

    Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

    2017-12-01

    The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

  19. Tracheostomy Decannulation: Suprastomal Granulation Tissue in ...

    Background: Suprastomal granulation tissue is a complication of tracheostomy which may make decannulation difficult and presents a therapeutic challenge to the Otorhinolaryngologists. The aims of this study therefore were to evaluate tracheostomy in black African population, determine the prevalence of suprastomal ...

  20. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    ANP) are present in the four regions of the atrial-auricular complex (two atria and two auricles). ANP-immunoreactivity was detected in all granules from the four regions. Ultrastructurally, atrial myocytes show the presence of very electron dense ...

  1. Water Filtration through Homogeneous Granulated Charge

    A. M. Krautsou

    2005-01-01

    Full Text Available General relationship for calculation of water filtration through homogeneous granulated charge has been obtained. The obtained relationship has been compared with experimental data. Discrepancies between calculated and experimental values do not exceed 6 % throughout the entire investigated range.

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

    ... 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: ...

  3. Intelligent system for improving dosage control

    Fabio Cosme Rodrigues dos Santos

    2017-02-01

    Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

  4. A brief history of dosage compensation

    depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

  5. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs.

    Lei, Zhixin; Liu, Qianying; Yang, Bing; Xiong, Jincheng; Li, Kun; Ahmed, Saeed; Hong, Liping; Chen, Pin; He, Qigai; Cao, Jiyue

    2017-01-01

    A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t 1/2β ), T max , and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different ( p enrofloxacin enteric-coated granules had significant potential for treating APP and MS

  6. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

    Zhixin Lei

    2017-05-01

    Full Text Available A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP and Mycoplasam suis (MS in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3 and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2β, Tmax, and area under the curve (AUC were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05 to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive

  7. Amylolytic hydrolysis of native starch granules affected by granule surface area.

    Kim, J C; Kong, B W; Kim, M J; Lee, S H

    2008-11-01

    Initial stage of hydrolysis of native starch granules with various amylolytic enzymes, alpha-amylase from Bacillus subtilis, glucoamylase I (GA-I) and II (GA-II) from Aspergillus niger, and beta-amylase from sweet potato showed that the reaction was apparently affected by a specific surface area of the starch granules. The ratios of the reciprocal of initial velocity of each amylolytic hydrolysis for native potato and maize starch to that for rice with the amylolytic enzymes were nearly equivalent to the ratio of surface area per mass of the 2 starch granules to that of rice, that is, 6.94 and 2.25, respectively. Thus, the reciprocal of initial velocity of each enzymatic hydrolysis as expressed in a Lineweaver-Burk plot was a linear function of the reciprocal of surface area for each starch granule. As a result, it is concluded that amylolytic hydrolysis of native starch granules is governed by the specific surface area, not by the mass concentration, of each granule.

  8. Pelletizing of NaF granules as adsorbent for fluorides of nuclear fuel materials, (2)

    Kimura, Syojiro; Tsutsui, Tenson; Kanagawa, Akira.

    1976-01-01

    Experimental studies on compressibility of NaF granules are investigated. Brittleness and porosity of a tableted pellet depend on compressive power applied to the granules. Relation of the compressive power and distortion of NaF granules agree with Kawakita's formula. About the brittleness of NaF pellet tableted with optional pressure, the follow experimental formula is formed between axial destructive power and compressive power. Dsub(p)=f.psup(n) Then, relation of the axial destructive power and porosity of NaF pellet is given from the above mentioned experimental formula and Kawakita's formula. At the lower value of the porosity than 0.4, the axial destructive power varies steeply as compared with variation of the porosity. At optional porosity, the brittleness of the tableted NaF pellet are lower than Harshow Chem. Co. NaF.HF pellet. So it requires some process raising the brittleness of the pellet after the compression. (auth.)

  9. Botanical origin, colour, granulation, and sensory properties of the Harenna forest honey, Bale, Ethiopia.

    Belay, Abera; Solomon, W K; Bultossa, Geremew; Adgaba, Nuru; Melaku, Samuel

    2015-01-15

    In this study, the Harenna forest honey samples were investigated with respect to their botanical origin, granulation, colour and sensory properties. Sixteen honey samples were collected from two representative sites (Chiri, C, and Wabero, W) using random sampling techniques. Botanical origin was investigated using qualitative pollen analysis by counting 500 pollen grains using harmonised methods of melissopalynology. Granulation, colour, and sensory properties of honey were determined by visual observation, using Pfund grader, acceptability and preference tests, respectively. Honey samples were also tested for tetracycline. Honey obtained from Wabero is originated dominantly from Syzygium guineense while Chiri was multifloral. The colour of honey ranged from 34 to 85 with light amber and extra light amber colours. The honey samples were free from tetracycline residue and form coarse granules slowly. Significant variation (p>0.05) in sensory preference and acceptability tests not observed due to hive types and locations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Thermophilic fermentative hydrogen production from starch-wastewater with bio-granules

    Akutsu, Yohei; Harada, Hideki [Department of Civil and Environmental Engineering, Tohoku University, 6-6-06 Aoba, Sendai, Miyagi 980-8579 (Japan); Lee, Dong-Yeol [Research Center for Material Cycles and Waste Management, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan); Chi, Yong-Zhi [Department of Environmental and Municipal Engineering, Tianjin Institute of Urban Construction, Jinjinggonglu 26, Tianjin 300384 (China); Li, Yu-You [Department of Environmental and Municipal Engineering, Tianjin Institute of Urban Construction, Jinjinggonglu 26, Tianjin 300384 (China); Department of Environmental Science, Tohoku University, 6-6-06 Aoba, Sendai, Miyagi 980-8579 (Japan); Yu, Han-Qing [School of Chemistry, University of Science and Technology of China, Hefei 230026 (China)

    2009-06-15

    In this study, the effects of the hydraulic retention time (HRT), pH and substrate concentration on the thermophilic hydrogen production of starch with an upflow anaerobic sludge bed (UASB) reactor were investigated. Starch was used as a sole substrate. Continuous hydrogen production was stably attained with a maximum H{sub 2} yield of 1.7 mol H{sub 2}/mol glucose. A H{sub 2}-producing thermophilic granule was successfully formed with diameter in the range of 0.5-4.0 mm with thermally pretreated methanogenic granules as the nuclei. The metabolic pathway of the granules was drastically changed at each operational parameter. The production of formic or lactic acids is an indication of the deterioration of hydrogen production for H{sub 2}-producing thermophilic granular sludge. (author)

  11. Structure and microhardness of alloy VT22 granules additionally doped with carbon and boron

    Sysoeva, N.V.; Polyakova, I.G.; Karpova, I.G.

    1996-01-01

    Aimed to improve heat resistance and strength of titanium base alloys due to carbon and boron additions (up to 0.3%) a study was made into regularities of phase decomposition in VT22 alloy during its rapid quenching from a liquid state on manufacturing granules 100-400 μm in size. Cooling rates on quenching were found to be sufficiently high to prevent precipitating carbides and borides. Subsequent annealing of granules promotes homogeneous precipitation of strengthening phases in the form of titanium carbides and borides, a reasonable amount of carbon and boron remaining in solid solution. An increase in microhardness of annealed granules reaches 20-25% compared to the standard alloy. 6 refs.; 2 figs.; 2 tabs

  12. Bacterial selection during the formation of early-stage aerobic granules in wastewater treatment systems operated under wash-out dynamics

    David Gregory Weissbrodt

    2012-09-01

    Full Text Available Aerobic granular sludge is attractive for high-rate biological wastewater treatment. Biomass wash-out conditions stimulate the formation of aerobic granules. Deteriorated performances in biomass settling and nutrient removal during start-up have however often been reported. The effect of wash-out dynamics was investigated on bacterial selection, biomass settling behavior, and metabolic activities during the formation of early-stage granules from activated sludge of two wastewater treatment plants (WWTP over start-up periods of maximum 60 days. Five bubble-column sequencing batch reactors were operated with feast-famine regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic starvation. Slow-settling fluffy granules were formed when an insufficient superficial air velocity (SAV; 1.8 cm s-1 was applied, when the inoculation sludge was taken from a WWTP removing organic matter only, or when reactors were operated at 30°C. Fast-settling dense granules were obtained with 4.0 cm s-1 SAV, or when the inoculation sludge was taken from a WWTP removing all nutrients biologically. However, only carbon was aerobically removed during start-up. Fluffy granules and dense granules were displaying distinct predominant phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives, respectively. The latter were predominant in dense granules independently from the feeding regime. A combination of insufficient solid retention time and of leakage of acetate into the aeration phase during intensive biomass wash-out was the cause for the proliferation of Zoogloea spp. in dense granules, and for the deterioration of BNR performances. It is however not certain that Zoogloea-like organisms are essential in granule formation. Optimal operation conditions should be elucidated for maintaining a balance between organisms with granulation propensity and nutrient removing organisms in order to form granules with BNR activities in

  13. Bacterial Selection during the Formation of Early-Stage Aerobic Granules in Wastewater Treatment Systems Operated Under Wash-Out Dynamics.

    Weissbrodt, David G; Lochmatter, Samuel; Ebrahimi, Sirous; Rossi, Pierre; Maillard, Julien; Holliger, Christof

    2012-01-01

    Aerobic granular sludge is attractive for high-rate biological wastewater treatment. Biomass wash-out conditions stimulate the formation of aerobic granules. Deteriorated performances in biomass settling and nutrient removal during start-up have however often been reported. The effect of wash-out dynamics was investigated on bacterial selection, biomass settling behavior, and metabolic activities during the formation of early-stage granules from activated sludge of two wastewater treatment plants (WWTP) over start-up periods of maximum 60 days. Five bubble-column sequencing batch reactors were operated with feast-famine regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic starvation. Slow-settling fluffy granules were formed when an insufficient superficial air velocity (SAV; 1.8 cm s(-1)) was applied, when the inoculation sludge was taken from a WWTP removing organic matter only, or when reactors were operated at 30°C. Fast-settling dense granules were obtained with 4.0 cm s(-1) SAV, or when the inoculation sludge was taken from a WWTP removing all nutrients biologically. However, only carbon was aerobically removed during start-up. Fluffy granules and dense granules were displaying distinct predominant phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives, respectively. The latter were predominant in dense granules independently from the feeding regime. A combination of insufficient solid retention time and of leakage of acetate into the aeration phase during intensive biomass wash-out was the cause for the proliferation of Zoogloea spp. in dense granules, and for the deterioration of BNR performances. It is however not certain that Zoogloea-like organisms are essential in granule formation. Optimal operation conditions should be elucidated for maintaining a balance between organisms with granulation propensity and nutrient removing organisms in order to form granules with BNR activities in short

  14. Effect of Slag Content and Hardening Accelerator Dosage on the Physico Mechanical Properties of Cement and Concrete

    Derabla, R.; Mokrani, I.; Benmalek, M.L.

    2011-01-01

    Our contribution consists at the study of the effect of (0 %, 0.2 % and 0.34 %) dosage of an hardening accelerating plasticizer (Plastocrete 160, produced by Sika Aldjazair) on the properties of normal mortar and concretes prepared with portland cement artificial of Hadjar Soud cement factory (Skikda - Algeria) with addition of (10 % and 20 %) of granulated blast furnace slag finely crushed of the El Hadjar blast furnace (Annaba - Algeria). The tests are focused to the physical and mechanical characteristics of elaborated materials to knowing: setting time, porosity, water absorption capacity and the test of compressive strength at 2, 7 and 28 days. The results obtained show clearly the reliability of the additive used to accelerate the hardening and to obtain high strengths at early age, which increase by increasing of the additive dosage. For the slag, its low hydraulic capacity does not make it profitable than at the long term (beyond 28 days). (author)

  15. Numerical study of a stochastic particle algorithm solving a multidimensional population balance model for high shear granulation

    Braumann, Andreas; Kraft, Markus; Wagner, Wolfgang

    2010-01-01

    This paper is concerned with computational aspects of a multidimensional population balance model of a wet granulation process. Wet granulation is a manufacturing method to form composite particles, granules, from small particles and binders. A detailed numerical study of a stochastic particle algorithm for the solution of a five-dimensional population balance model for wet granulation is presented. Each particle consists of two types of solids (containing pores) and of external and internal liquid (located in the pores). Several transformations of particles are considered, including coalescence, compaction and breakage. A convergence study is performed with respect to the parameter that determines the number of numerical particles. Averaged properties of the system are computed. In addition, the ensemble is subdivided into practically relevant size classes and analysed with respect to the amount of mass and the particle porosity in each class. These results illustrate the importance of the multidimensional approach. Finally, the kinetic equation corresponding to the stochastic model is discussed.

  16. Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation

    Angelica Aguilera-Gomez

    2017-07-01

    Full Text Available Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein.

  17. Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation.

    Aguilera-Gomez, Angelica; Zacharogianni, Margarita; van Oorschot, Marinke M; Genau, Heide; Grond, Rianne; Veenendaal, Tineke; Sinsimer, Kristina S; Gavis, Elizabeth R; Behrends, Christian; Rabouille, Catherine

    2017-07-25

    Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Factors Involved in Sludge Granulation under Anaerobic Conditions

    Jalal Shayegan

    2011-03-01

    Full Text Available This paper investigates the effects of factors involved in sludge anaerobic granulation. Granulated sludge formation is the main parameter contributing to the success of UASB reactors. Anaerobic granulation leads to reduced reactor size, space requirement, and investment costs. Operation costs are also greatly reduced due to lack of aeration. An important parameter affecting process performance is the size of sludge granules; the factors involved in granule size will be investigated. Some of the important parameters of anaerobic sludge granulation are: existence of growth cores as inert particles or granulated sludge, process operational conditions (Sludge Loading Rate and Organic Loading Rate, Loading rate increase and …, and environment conditions (nutrients, temperature, pH, combination and ….

  19. Giant renin secretory granules in beige mouse renal afferent arterioles

    Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

    1997-01-01

    The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

  20. Modifying the properties of finely ground limestone by tumbling granulation

    Macho, Oliver; Eckert, Maroš; Tomášová, Barbora; Peciar, Peter; Ščasný, Martin; Fekete, Roman; Peciar, Marián

    2016-06-01

    Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  1. Modifying the properties of finely ground limestone by tumbling granulation

    Macho Oliver

    2016-06-01

    Full Text Available Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  2. Increased accuracy of starch granule type quantification using mixture distributions.

    Tanaka, Emi; Ral, Jean-Phillippe F; Li, Sean; Gaire, Raj; Cavanagh, Colin R; Cullis, Brian R; Whan, Alex

    2017-01-01

    The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority of the studies that have considered granule types analyse them based on a size threshold rather than chemical composition. This is understandable due to the expense of separating starch into different types. While the use of a size threshold to classify granule type is a low-cost measure, this results in misclassification. We present an alternative, statistical method to quantify the proportion of granule types by a fit of the mixture distribution, along with an R package, a web based app and a video tutorial for how to use the web app to enable its straightforward application. Our results show that the reliability of the genotypic effects increase approximately 60% using the proportions of the A-type and B-type granule estimated by the mixture distribution over the standard size-threshold measure. Although there was a marginal drop in reliability for C-type granules. The latter is likely due to the low observed genetic variance for C-type granules. The determination of the proportion of granule types from size-distribution is better achieved by using the mixing probabilities from the fit of the mixture distribution rather than using a size-threshold.

  3. Optimizing the dosage of stabilizing chemical

    Harjula, Tomi

    2013-01-01

    A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

  4. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Modified granulation of red mud by weak gelling and its application to stabilization of Pb.

    Luo, Hui-li; Huang, Sheng-sheng; Luo, Lin; Wu, Gen-yi; Liu, Yan

    2012-08-15

    This study presents a novel modification of red mud (RM) with cementitious materials by rotary drum granulation under partial hydration. Admixtures and surfactants were applied to improve the microspore structure of red mud-based granules in order to stabilize Pb steadily. Through XRD and SEM-EDS analyses, it was demonstrated that calcite, the main alkali in RM, was partially concreted and coated. Compared to pH 12.47 for RM, the lowest pH of the granules was 10.66 implying that the release of OH(-) from hydrolysis and decomposition was decreased. Based on stabilization of Pb, influence on soil properties and forming qualities, composition of the optimum granule PSP was determined as 5% cement, 5% gypsum, 1% rice straw, and 0.1% emulsifier OP-10. Within a 90 d remediation, immobilization of ionic Pb in a 500 mg kg(-1) Pb-contaminated artificial soil was 9.85 mg kg(-1) at day 30 with 5% PSP2 as substitute. Furthermore, the reverse increase diminished as the final concentration was 11.13 mg kg(-1) while it was 14.25 mg kg(-1) by RM. The increase of residual Pb was 122.61%, which was better than the 83.92% of RM. Particularly, the highest pH in mine soil was 11.09 at day 1 with RM, but the decrease of ionic Pb was 46.26%. Meanwhile, a significant deviation from the control soil zeta-potential lasted longer and the recovery was more difficult, as compared to the granules. Therefore, a granulated modification of RM is shown to be very important when aiming at steady release of OH(-) to improve the later stabilization of Pb. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

    Hermann Cuntz

    2014-03-01

    passive and/or active membrane properties, the plastic remodeling of dendrites following lesion of entorhinal inputs to granule cells will boost the efficacy of action potential backpropagation significantly and maintain their firing rate. Our results suggest that in addition to synaptic and intrinsic plasticity, a novel form of homeostatic plasticity,structural plasticity due todendritic remodeling.is operating in denervated neurons.

  7. Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons.

    Srivastava, Rupali; Kumar, Manoj; Peineau, Stéphane; Csaba, Zsolt; Mani, Shyamala; Gressens, Pierre; El Ghouzzi, Vincent

    2013-04-01

    Directing differentiation of embryonic stem cells (ESCs) to specific neuronal subtype is critical for modeling disease pathology in vitro. An attractive means of action would be to combine regulatory differentiation factors and extrinsic inductive signals added to the culture medium. In this study, we have generated mature cerebellar granule neurons by combining a temporally controlled transient expression of Math1, a master gene in granule neuron differentiation, with inductive extrinsic factors involved in cerebellar development. Using a Tetracyclin-On transactivation system, we overexpressed Math1 at various stages of ESCs differentiation and found that the yield of progenitors was considerably increased when Math1 was induced during embryonic body stage. Math1 triggered expression of Mbh1 and Mbh2, two target genes directly involved in granule neuron precursor formation and strong expression of early cerebellar territory markers En1 and NeuroD1. Three weeks after induction, we observed a decrease in the number of glial cells and an increase in that of neurons albeit still immature. Combining Math1 induction with extrinsic factors specifically increased the number of neurons that expressed Pde1c, Zic1, and GABAα6R characteristic of mature granule neurons, formed "T-shaped" axons typical of granule neurons, and generated synaptic contacts and action potentials in vitro. Finally, in vivo implantation of Math1-induced progenitors into young adult mice resulted in cell migration and settling of newly generated neurons in the cerebellum. These results show that conditional induction of Math1 drives ESCs toward the cerebellar fate and indicate that acting on both intrinsic and extrinsic factors is a powerful means to modulate ESCs differentiation and maturation into a specific neuronal lineage. Copyright © 2012 AlphaMed Press.

  8. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  9. TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2.

    Rayman, Joseph B; Karl, Kevin A; Kandel, Eric R

    2018-01-02

    Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity. A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1). Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN. Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN. In addition, Zn 2+ is released in cells treated with arsenite, before stress granule formation. These findings suggest that Zn 2+ is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Early x-irradiation of rats. Part 2. Effect of granule cells and their dendrodendritic synapses in the olfactory bulb

    Halasz, N

    1987-01-01

    Low, repeated doses of X-rays from a Co/sup 60/ source were used to impair the development of the granule cells and their dendritic terminals in the olfactory bulb, and the resulting effect was studied under light and electron microscopes at 9 days of age. Irradiation of rats from embryonic day 18 (in utero) to postnatal day 5 resulted, among others, in maldevelopment of the (internal) granule cell and external plexiform layers. This was accompanied by a decrease in the number and the density of the granule cells, and the remaining granule cells contained less ribosomes, regardless of their position within the layer. This implies that both supposed subtypes of granule cells were effected. In the external plexiform layer, a reduced number of mature dendrodendritic synapses and signs of harmed granule gemmules were observed. The results suggest that intrauterinal plus postnatal irradiation with low, repeated doses of X-rays may be an effective tool impairing the development of prenatally forming neurons.

  11. Oscillating behavior of carbohydrate granule formation and dinitrogen fixation in the cyanobacterium Cyanothece sp. strain ATCC 51142

    Schneegurt, M. A.; Sherman, D. M.; Nayar, S.; Sherman, L. A.; Mitchell, C. A. (Principal Investigator)

    1994-01-01

    It has been shown that some aerobic, unicellular, diazotrophic cyanobacteria temporally separate photosynthetic O2 evolution and oxygen-sensitive N2 fixation. Cyanothece sp. ATCC strain 51142 is an aerobic, unicellular, diazotrophic cyanobacterium that fixes N2 during discrete periods of its cell cycle. When the bacteria are maintained under diurnal light-dark cycles, N2 fixation occurs in the dark. Similar cycling is observed in continuous light, implicating a circadian rhythm. Under N2-fixing conditions, large inclusion granules form between the thylakoid membranes. Maximum granulation, as observed by electron microscopy, occurs before the onset of N2 fixation, and the granules decrease in number during the period of N2 fixation. The granules can be purified from cell homogenates by differential centrifugation. Biochemical analyses of the granules indicate that these structures are primarily carbohydrate, with some protein. Further analyses of the carbohydrate have shown that it is a glucose polymer with some characteristics of glycogen. It is proposed that N2 fixation is driven by energy and reducing power stored in these inclusion granules. Cyanothece sp. strain ATCC 51142 represents an excellent experimental organism for the study of the protective mechanisms of nitrogenase, metabolic events in cyanobacteria under normal and stress conditions, the partitioning of resources between growth and storage, and biological rhythms.

  12. Loss of Melanin by Eye Retinal Pigment Epithelium Cells Is Associated with Its Oxidative Destruction in Melanolipofuscin Granules.

    Dontsov, A E; Sakina, N L; Ostrovsky, M A

    2017-08-01

    The effect of superoxide radicals on melanin destruction and degradation of melanosomes isolated from cells of retinal pigment epithelium (RPE) of the human eye was studied. We found that potassium superoxide causes destruction of melanin in melanosomes of human and bovine RPE, as well as destruction of melanin from the ink bag of squid, with the formation of fluorescent decay products having an emission maximum at 520-525 nm. The initial kinetics of the accumulation of the fluorescent decay products is linear. Superoxide radicals lead simultaneously to a decrease in the number of melanosomes and to a decrease in concentration of paramagnetic centers in them. Complete degradation of melanosomes leads to the formation of a transparent solution containing dissolved proteins and melanin degradation products that do not exhibit paramagnetic properties. To completely degrade one melanosome of human RPE, 650 ± 100 fmol of superoxide are sufficient. The concentration of paramagnetic centers in a melanolipofuscin granule of human RPE is on average 32.5 ± 10.4% (p melanin undergoing a destruction process in these granules. RPE cells also contain intermediate granules that have an EPR signal with a lower intensity than that of melanolipofuscin granules, but higher than that of lipofuscin granules. This signal is due to the presence of residual melanin in these granules. Irradiation of a mixture of melanosomes with lipofuscin granules with blue light (450 nm), in contrast to irradiation of only melanosomes, results in the appearance of fluorescent melanin degradation products. We suggest that one of the main mechanisms of age-related decrease in melanin concentration in human RPE cells is its destruction in melanolipofuscin granules under the action of superoxide radicals formed during photoinduced oxygen reduction by lipofuscin fluorophores.

  13. Batch study, equilibrium and kinetics of adsorption of naphthalene using waste tyre rubber granules

    Felix A. Aisien

    2014-04-01

    Full Text Available The potential use of waste tyre rubber granules (WTRG for the batch adsorption of naphthalene from aqueous solutions was investigated. The effect of various operational variables such as contact time, initial naphthalene concentration, adsorbent dose, size of adsorbent particles, and temperature of solution on the adsorption capacity of WTRG was evaluated. The adsorption of naphthalene by WTRG was a fast kinetic process with an equilibrium contact time of 60 min. A low temperature (5°C, small adsorbent particle size (0.212 mm and higher adsorbent dosage favored the adsorption process. Results of isotherm studies revealed that adsorption of naphthalene was best described by the Langmuir isotherm equation (R2=0.997 while the kinetics of the process was best described by the Lagergren pseudofirst order kinetic equation (R2=0.998. This study has demonstrated the suitability of WTRG for the removal of naphthalene from aqueous solution.

  14. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the

  15. Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

    Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

    2014-04-01

    Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All

  16. Validation of HPLC, DPPH• and nitrosation methods for mesalamine determination in pharmaceutical dosage forms Validação dos métodos de CLAE, DPPH• e nitrosação para determinação de mesalazina em formas farmacêuticas

    Janice Aparecida Rafael

    2007-03-01

    Full Text Available Mesalamine (5-aminosalicylic acid, 5-ASA is used because of its local effects in the treatment of inflammatory bowel disease. Therefore, the aims of this work were to compare and validate three analytical methods for the quality control of commercial coated tablets containing 5-ASA: high performance liquid chromatography (HPLC, 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH• and nitrosation. The parameters linearity, precision and accuracy were studied in this work. HPLC with ultraviolet detection at 254 nm was carried out with a C18 column and a mobile phase constituted of 30 mmol/L monobasic phosphate buffer (pH 7.0 and methanol (70:30; v/v, with 25% tetrabutylammonium hydrogen sulphate. The DPPH• method was performed at 517 nm and using 100 mmol/L acetate buffer, pH 5.5, ethanol and 250 µmol/L ethanolic solution of DPPH•. The nitrosation method was accomplished by using a platinum electrode and standard 0.1 mol/L sodium nitrite as titrant solution. Repeatability (intra-day and intermediate precision (inter-day, expressed as RSD, were lower than 3%. The experimental recoveries were between 72.5 and 99.9%. Statistical analysis by one-way ANOVA, followed by the multiple comparison test of Bonferroni showed no significant difference among the three methods. All proposed methods can be used for the reliable quantitation of 5-ASA in pharmaceutical dosage forms.Mesalazina (ácido 5-aminosalicílico, 5-ASA é utilizado devido seu efeito local no tratamento de doença inflamatória intestinal. Assim, o objetivo deste trabalho foi comparar e validar três métodos analíticos para o controle de qualidade de comprimidos comerciais revestidos contendo 5-ASA: cromatografia líquida de alta eficiência (CLAE, radical 1,1-difenil-2-picril-hidrazil (DPPH• e nitrosação. Os parâmetros linearidade, precisão e exatidão foram estudados neste trabalho. CLAE com detecção ultravioleta em 254 nm foi realizada utilizando coluna C18 e a eluição em fase m

  17. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat

    2008-01-01

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  18. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat [Pamukkale University, Department of Radiology, School of Medicine, Denizli (Turkey)

    2008-10-15

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  19. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

    Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de; Zanetti, María Natalia [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Fukuda, Mitsunori [Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Fissore, Rafael A. [Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 North Pleasant Street, Amherst, MA 01003 (United States); Mayorga, Luis S. [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Michaut, Marcela A., E-mail: mmichaut@gmail.com [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (Argentina)

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of

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

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

    2013-01-01

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

  1. Understanding the glass-forming ability of active pharmaceutical ingredients for designing supersaturating dosage forms.

    Kawakami, Kohsaku; Usui, Toshinori; Hattori, Mitsunari

    2012-09-01

    Amorphous solid dispersions have great potential for enhancing oral absorption of poorly soluble drugs. Crystallization behavior during storage and after exposure to aqueous media must be examined in detail for designing stable and effective amorphous formulations, and it is significantly affected by the intrinsic properties of an amorphous drug. Many attempts have been made to correlate various thermodynamic parameters of pharmaceutical glasses with their crystallization behavior; however, variations in model drugs that could be used for such investigation has been limited because the amorphous characteristics of drugs possessing a high crystallization tendency are difficult to evaluate. In this study, high-speed differential scanning calorimetry, which could inhibit their crystallization using high cooling rates up to 2000°C/s, was employed for assessing such drugs. The thermodynamic parameters of the glasses, including glass transition temperature (T(g)) and fragility, were obtained to show that their crystallization tendency cannot be explained simply by the parameters, although there have been general thought that fragility may be correlated with crystallization tendency. Also investigated was correlation between the thermodynamic parameters and crystallization tendency upon contact with water, which influences in vivo efficacy of amorphous formulations. T(g) was correlated well with the crystallization tendency upon contact with water. Copyright © 2012 Wiley Periodicals, Inc.

  2. Evaluation of the binding effect of human serum albumin on the properties of granules.

    Kristó, Katalin; Bajdik, János; Eros, István; Pintye-Hódi, Klára

    2008-11-01

    The main objective of this study was the application of a solution of human serum albumin as a granulating fluid. The properties of the granules formed were evaluated and compared with those when a conventional binder was applied in the same concentration. The powder mixture contained a soluble (mannitol) and an insoluble component (different types of cellulose). The protein solution applied exerted an appropriate aggregating effect if the system contained microcrystalline celluloses. Powdered cellulose was not suitable for the granulation with human serum albumin solution. As compared with the same concentration of the conventionally applied cellulose ethers as binder, the prepared granules exhibited a larger particle size, a significantly better compressibility, a higher breaking hardness and a favourable deformation process. These findings mainly reflect the good adhesive properties of the protein. The best compressibility and mechanical behaviour were attained on the application of the microcrystalline cellulose Vivapur type 105. This favourable behaviour may be connected with the wettability of cellulose. These results suggest that the formulation of tablets may be easier from an active agent in the serum that binds to albumin (e.g. interferon) since the amount of additives (binder) can be reduced.

  3. Microbial Community Composition and Ultrastructure of Granules from a Full-Scale Anammox Reactor

    Gonzalez-Gil, Graciela

    2014-12-11

    Granules in anammox reactors contain besides anammox bacteria other microbial communities whose identity and relationship with the anammox bacteria are not well understood. High calcium concentrations are often supplied to anammox reactors to obtain sufficient bacterial aggregation and biomass retention. The aim of this study was to provide the first characterization of bacterial and archaeal communities in anammox granules from a full-scale anammox reactor and to explore on the possible role of calcium in such aggregates. High magnification imaging using backscattered electrons revealed that anammox bacteria may be embedded in calcium phosphate precipitates. Pyrosequencing of 16S rRNA gene fragments showed, besides anammox bacteria (Brocadiacea, 32 %), substantial numbers of heterotrophic bacteria Ignavibacteriacea (18 %) and Anaerolinea (7 %) along with heterotrophic denitrifiers Rhodocyclacea (9 %), Comamonadacea (3 %), and Shewanellacea (3 %) in the granules. It is hypothesized that these bacteria may form a network in which heterotrophic denitrifiers cooperate to achieve a well-functioning denitrification system as they can utilize the nitrate intrinsically produced by the anammox reaction. This network may provide a niche for the proliferation of archaea. Hydrogenotrophic methananogens, which scavenge the key fermentation product H2, were the most abundant archaea detected. Cells resembling the polygon-shaped denitrifying methanotroph Candidatus Methylomirabilis oxyfera were observed by electron microscopy. It is hypothesized that the anammox process in a full-scale reactor triggers various reactions overall leading to efficient denitrification and a sink of carbon as biomass in anammox granules.

  4. DETECTION OF VORTEX TUBES IN SOLAR GRANULATION FROM OBSERVATIONS WITH SUNRISE

    Steiner, O.; Franz, M.; Bello Gonzalez, N.; Nutto, Ch.; Rezaei, R.; Schmidt, W.; Martinez Pillet, V.; Bonet Navarro, J. A.; Del Toro Iniesta, J. C.; Domingo, V.; Solanki, S. K.; Barthol, P.; Gandorfer, A.; Knoelker, M.

    2010-01-01

    We have investigated a time series of continuum intensity maps and corresponding Dopplergrams of granulation in a very quiet solar region at the disk center, recorded with the Imaging Magnetograph eXperiment (IMaX) on board the balloon-borne solar observatory SUNRISE. We find that granules frequently show substructure in the form of lanes composed of a leading bright rim and a trailing dark edge, which move together from the boundary of a granule into the granule itself. We find strikingly similar events in synthesized intensity maps from an ab initio numerical simulation of solar surface convection. From cross sections through the computational domain of the simulation, we conclude that these granular lanes are the visible signature of (horizontally oriented) vortex tubes. The characteristic optical appearance of vortex tubes at the solar surface is explained. We propose that the observed vortex tubes may represent only the large-scale end of a hierarchy of vortex tubes existing near the solar surface.

  5. Microbial community composition and ultrastructure of granules from a full-scale anammox reactor.

    Gonzalez-Gil, Graciela; Sougrat, Rachid; Behzad, Ali R; Lens, Piet N L; Saikaly, Pascal E

    2015-07-01

    Granules in anammox reactors contain besides anammox bacteria other microbial communities whose identity and relationship with the anammox bacteria are not well understood. High calcium concentrations are often supplied to anammox reactors to obtain sufficient bacterial aggregation and biomass retention. The aim of this study was to provide the first characterization of bacterial and archaeal communities in anammox granules from a full-scale anammox reactor and to explore on the possible role of calcium in such aggregates. High magnification imaging using backscattered electrons revealed that anammox bacteria may be embedded in calcium phosphate precipitates. Pyrosequencing of 16S rRNA gene fragments showed, besides anammox bacteria (Brocadiacea, 32%), substantial numbers of heterotrophic bacteria Ignavibacteriacea (18%) and Anaerolinea (7%) along with heterotrophic denitrifiers Rhodocyclacea (9%), Comamonadacea (3%), and Shewanellacea (3%) in the granules. It is hypothesized that these bacteria may form a network in which heterotrophic denitrifiers cooperate to achieve a well-functioning denitrification system as they can utilize the nitrate intrinsically produced by the anammox reaction. This network may provide a niche for the proliferation of archaea. Hydrogenotrophic methananogens, which scavenge the key fermentation product H2, were the most abundant archaea detected. Cells resembling the polygon-shaped denitrifying methanotroph Candidatus Methylomirabilis oxyfera were observed by electron microscopy. It is hypothesized that the anammox process in a full-scale reactor triggers various reactions overall leading to efficient denitrification and a sink of carbon as biomass in anammox granules.

  6. Isolated Poly(3-Hydroxybutyrate) (PHB) Granules Are Complex Bacterial Organelles Catalyzing Formation of PHB from Acetyl Coenzyme A (CoA) and Degradation of PHB to Acetyl-CoA▿

    Uchino, Keiichi; Saito, Terumi; Gebauer, Birgit; Jendrossek, Dieter

    2007-01-01

    Poly(3-hydroxybutyrate) (PHB) granules isolated in native form (nPHB granules) from Ralstonia eutropha catalyzed formation of PHB from 14C-labeled acetyl coenzyme A (CoA) in the presence of NADPH and concomitantly released CoA, revealing that PHB biosynthetic proteins (acetoacetyl-CoA thiolase, acetoacetyl-CoA reductase, and PHB synthase) are present and active in isolated nPHB granules in vitro. nPHB granules also catalyzed thiolytic cleavage of PHB in the presence of added CoA, resulting in...

  7. Dosage of DTPA administration by inhalation

    Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

    2000-01-01

    The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

  8. New developments on transition radiation detectors using superconducting granules

    Yuan, L.C.L.

    1977-01-01

    By raising slightly either the temperature or the magnetic field to above that of the critical temperature or the critical magnetic field, the type I superconducting granules would still remain in the superconducting state which becomes a metastable state and is called the superheated superconducting state. If a relativistic charged particle incident on such a granule which is located in a colloidal suspension has imported to it an energy that is above the threshold energy (for state flipping) of the granule then it would flip to the normal state. The threshold energy of a granule is a function of the square of its radius, whereas the energy loss of a charged particle due to ionization is linearly proportional to the radius. The size of the granule can be pre-determined to be such that its threshold energy is slightly above the ionization loss of a relativistic charged particle. Then the traversal of the charged particle through such a granule would not affect the superconducting state of the granule unless a transition x-ray radiation is emitted at the surface of the granule by the traversing particle and the x-ray transition radiation is immediately absorbed either in total or partially by the metallic granule causing it to flip to the normal state. The total intensity of the x-ray transition radiation is linearly proportional to the Lorentz factor γ of the traversing particle, and the number of granules flipped would also be a measure of γ. Three methods for detecting the flipping of granules from the superconducting state to the normal state are described. They include the frequency measuring method, the SQUID method, and the pulse method with low noise amplifier system

  9. The biology and dynamics of mammalian cortical granules

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  10. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    Bagchi, Samik; Lamendella, Regina; Strutt, Steven; Van Loosdrecht, Mark C. M.; Saikaly, Pascal

    2016-01-01

    to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all

  11. Granule properties of paracetamol made with Bombax ceiba gum ...

    Bombax ceiba gum was extracted from the calyx of the Bombax flower using both hot and cold water extraction method. The gum was used as binder to prepare paracetamol granules in concentrations of 1, 1.5, 2, and 3 %. Acacia gum was used to prepare the standard at the same concentrations. The granule properties of ...

  12. Proximate analysis of Sweet Potato Toasted Granules | Meludu ...

    Sweet potato is an important root crop in the food system of many African countries. The yield, nutrition and economic potential of sweet potato have been identified as very high. In this study, sweet potato was processed and toasted into granules. The proximate analysis performed on the toasted granules showed protein, ...

  13. Application of granulating of tires; Aplicaciones de granulado de NFUs

    Jimenez Justicia, A.

    2001-07-01

    At present, used tires are mainly used as fuel, retreading and granulating of tires. In this article. I will focus on the last option, talking about some of the multiple applications and going into detail of the making process of the granulation of used tires in a recycling plant. (Author)

  14. Roll compaction and granulation system for nuclear fuel material

    Goldmann, L.H. Jr.; Holley, C.C.

    1981-01-01

    A roll compaction and roll granulation system has been designed and fabricated to replace conventional preslugging and crushing operations typically used in the fabrication of mixed oxide nuclear fuel pellets. This equipment will be of maintenance advantage with only the compaction and granulation rolls inside containment. The prototype is being tested and the results will be reported within a year

  15. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, ( 3 H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines

  16. Autophagy meets fused in sarcoma-positive stress granules.

    Matus, Soledad; Bosco, Daryl A; Hetz, Claudio

    2014-12-01

    Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Osseous drill holes to promote granulation tissue: Radiologic appearance

    Resnik, C.S.; Reiner, B.I.; Diaconis, J.N.; Goldberg, N.H.

    1991-01-01

    Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.)

  18. Method for the treatment of waste water with sludge granules

    Van Loosdrecht, M.C.; De Kreuk, M.K.

    2004-01-01

    The invention relates to a method for the treatment of waste water comprising an organic nutrient. According to the invention, the waste water is in a first step fed to sludge granules, after the supply of the waste water to be treated the sludge granules are fluidised in the presence of an

  19. Consolidating nanoparticles in micron-sized granules using spray drying

    Lindeloev, J S; Wahlberg, M

    2011-01-01

    Suspensions of nanoparticles (SiO 2 , SiC, TiO2, CNT, Nanoclay and Hydroxyapatite) were spray dried to produce dry granulated products. The nanoparticles were consolidated in granules making them more convenient and safer to use in further processing compared to handling of nanopowders.

  20. ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics.

    Gal, Jozsef; Kuang, Lisha; Barnett, Kelly R; Zhu, Brian Z; Shissler, Susannah C; Korotkov, Konstantin V; Hayward, Lawrence J; Kasarskis, Edward J; Zhu, Haining

    2016-10-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. The co-localization was also observed in fibroblast cells derived from familial ALS patient carrying SOD1 mutation L144F. Mutant SOD1, unlike wild-type SOD1, interacted with G3BP1 in an RNA-independent manner. Moreover, the interaction is specific for G3BP1 since mutant SOD1 showed little interaction with four other RNA-binding proteins implicated in ALS. The RNA-binding RRM domain of G3BP1 and two particular phenylalanine residues (F380 and F382) are critical for this interaction. Mutant SOD1 delayed the formation of G3BP1- and TIA1-positive stress granules in response to hyperosmolar shock and arsenite treatment in N2A cells. In summary, the aberrant mutant SOD1-G3BP1 interaction affects stress granule dynamics, suggesting a potential link between pathogenic SOD1 mutations and RNA metabolism alterations in ALS.