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

PubMed

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.

Preparation of delayed release tablet dosage forms by compression coating: effect of coating material on theophylline release.

PubMed

El-Malah, Yasser; Nazzal, Sami

2010-06-01

In this study, compression-coated tablets were prepared and examined by real-time swelling/erosion analysis and dissolution studies. Of the coating materials, PVP showed no swelling behavior and had no impact on theophylline release. Polyox(®) exhibited swelling behavior of an entangled polymer, which was reflected in its > 14-hour delayed-release profile. Hydroxypropyl methylcellulose (HPMC), which revealed the characteristics of a disentangled polymer, caused a 2-h delay in theophylline release. Based on preliminary texture analysis data, Polyox(®)/PVP blends were used as coating materials to manipulate the onset of drug release from the compression-coated tablets. Of the blends, at a 1:1 ratio, for example, resulted in a burst release after 10 h, which demonstrated the feasibility of preparing delayed release dosage forms by compression coating. Furthermore, it was feasible to predict the dissolution behavior of polymers from their swelling/erosion data, which were generated from texture analysis.

Evaluation of the viability of Lactobacillus spp. after the production of different solid dosage forms.

PubMed

Brachkova, Mariya I; Duarte, Aida; Pinto, João F

2009-09-01

The work aims to provide evidence on the viability of Lactobacillus spp. and a spore form of Bacillus subtilis from nonprocessed bacteria to coated dosage forms (i.e., mini-tablets, pellets, and their coated forms). Lactobacillus spp. were cultivated overnight in MRS broth (10(9) cfu/mL) and B. subtilis spores were produced on plate count agar (10(7) cfu/mL) for 2 weeks. Bacteria and spores were freeze-dried in skim milk enriched with glycerol. The cakes were further processed into tablets (2.5 mm diameter) by direct compression with or without microcrystalline cellulose and inulin. Pellets (1-1.4 mm diameter) were produced by extrusion-spheronization of bacterial and spore suspensions with microcrystalline cellulose, lactose, inulin, and skim milk. Both tablets and pellets were film coated. The properties of the dosage forms, particularly the bacterial viability, were evaluated immediately after production and throughout storage for 6 months at 4 degrees C. The study has shown that for an adequate stabilization of the bacteria a protective matrix (e.g., skim milk) and cryoprotectors (e.g., glycerol) must be present at early stages of bacterial de-hydration. Tabletting had a less deleterious effect (<2 log units) on bacteria when compared to pelletization (in some cases 3 log units). Enteric coating (15%, w/w) of either tablets or pellets did not affect the viability of the bacteria.

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

PubMed

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.

Manufacturing Solid Dosage Forms from Bulk Liquids Using the Fluid-bed Drying Technology.

PubMed

Qi, Jianping; Lu, Y I; Wu, Wei

2015-01-01

Solid dosage forms are better than liquid dosage forms in many ways, such as improved physical and chemical stability, ease of storage and transportation, improved handling properties, and patient compliance. Therefore, it is required to transform dosage forms of liquid origins into solid dosage forms. The functional approaches are to absorb the liquids by solid excipients or through drying. The conventional drying technologies for this purpose include drying by heating, vacuum-, freeze- and spray-drying, etc. Among these drying technologies, fluidbed drying emerges as a new technology that possesses unique advantages. Fluid-bed drying or coating is highly efficient in solvent removal, can be performed at relatively low temperatures, and is a one-step process to manufacture formulations in pellet forms. In this article, the status of the art of manufacturing solid dosage forms from bulk liquids by fluid-bed drying technology was reviewed emphasizing on its application in solid dispersion, inclusion complexes, self-microemulsifying systems, and various nanoscale drug delivery systems.

A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

PubMed

Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

2010-10-01

An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms.

PubMed

Mwesigwa, Enosh; Basit, Abdul W

2016-01-30

Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating.

PubMed

Nguyen, Cung An; Konan-Kouakou, Yvette Niamien; Allémann, Eric; Doelker, Eric; Quintanar-Guerrero, David; Fessi, Hatem; Gurny, Robert

2006-07-28

The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage forms.

How to adjust desired drug release patterns from ethylcellulose-coated dosage forms.

PubMed

Siepmann, F; Hoffmann, A; Leclercq, B; Carlin, B; Siepmann, J

2007-06-04

The aim of this study was to provide an easy and efficient tool to adjust desired drug release kinetics from (aqueous) ethylcellulose-coated solid dosage forms and to better understand the underlying mass transport mechanisms. Pure ethylcellulose films are poorly permeable for many substances and can result in very low release rates for certain drugs from coated dosage forms, if the film coatings are completely formed and remain intact upon exposure to the release media. To increase the permeability of the polymeric membranes, different amounts of a water-soluble poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) were added to an aqueous ethylcellulose dispersion (Aquacoat ECD). Importantly, the presence of only a low percentage of this hydrophilic copolymer significantly increased the resulting water uptake rate and extent, dry weight loss and drug permeability of the films. In contrast to hydroxypropyl methylcellulose (HPMC), the PVA-PEG graft copolymer does not cause flocculation of the colloidal coating dispersion (leading to potentially variable release rates). Interestingly, the transport of water as well as of the model drug theophylline through the polymeric networks was primarily controlled by pure diffusion. The penetration kinetics could be quantitatively described by Fick's law of diffusion, irrespective of the type of release medium and PVA-PEG graft copolymer content. Most important from a practical point of view, a broad spectrum of pH-independent drug release rates can easily be obtained from drug-loaded pellets by simply varying the PVA-PEG graft copolymer content. An appropriate curing step after coating is required, but interestingly the investigated curing conditions (differing in time and relative humidity) resulted in very similar drug release patterns, indicating that stable film structures are likely to be achieved.

Development of pressure-sensitive dosage forms with a core liquefying at body temperature.

PubMed

Wilde, Lisa; Bock, Mona; Wolf, Marieke; Glöckl, Gunnar; Garbacz, Grzegorz; Weitschies, Werner

2014-04-01

Pressure-sensitive dosage forms have been developed that are intended for pulsatile delivery of drugs to the proximal small intestine. The novel dosage forms are composed of insoluble shell and either a hard fat W32 or polyethylene glycol (PEG) 1000 core that are both liquidizing at body temperature. The release is triggered by predominant pressure waves such as contractions of the pylorus causing rupture of the shell and an immediate emptying of the liquefied filling containing the active ingredient. In consequence immediately after the trigger has been effective the total amount of the drug is intended to be available for absorption in the upper small intestine. Both core types were coated with a cellulose acetate film that creates a pressure-sensitive shell in which mechanical resistance is depending on the coating thickness. Results of the texture analysis confirmed a correlation between the polymer load of the coating and the mechanical resistance. The dissolution test performed under conditions of physiological meaningful mechanical stress showed that the drug release is triggered by pressure waves of ⩾300 mbar which are representing the maximal pressure occurring during the gastric emptying. Copyright © 2013 Elsevier B.V. All rights reserved.

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

PubMed

Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

2010-02-01

Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

Investigation of a new pH-responsive nanoparticulate pore former for controlled release enteric coating with improved processability and stability.

PubMed

Chen, Kuan; Chang, Hao Han R; Shalviri, Alireza; Li, Jason; Lugtu-Pe, Jamie Anne; Kane, Anil; Wu, Xiao Yu

2017-11-01

Water-soluble polymers are often used as pore formers to tailor permeability of film-forming hydrophobic polymers on coated dosage forms. However, their addition to a coating formulation could significantly increase the viscosity thus making the coating process difficult. Moreover, the dissolution of pore formers after oral administration could compromise film integrity resulting in undesirable, inconsistent release profiles. Therefore, a non-leaching, pH-responsive nanoparticulate pore former is proposed herein to preserve film integrity and maintain pH-dependent permeability. Poly(methacrylic acid)-polysorbate 80-grafted-starch terpolymer nanoparticles (TPNs) were incorporated within an ethylcellulose (EC) film (TPN-EC) by casting or spray coating. TPNs at 10%wt (pore former level) only increased viscosity of EC coating suspension slightly while conventional pore formers increased the viscosity by 490-11,700%. Negligible leaching of TPNs led to superior mechanical properties of TPN-EC films compared to Eudragit® L-EC films. As pH increased from 1.2 to 6.8, TPN-EC films with 10% pore former level exhibited an 8-fold higher diltiazem permeability compared to Eudragit® L-EC films. The pH-dependent drug release kinetics of diltiazem HCl beads coated with TPN-EC films was tunable by adjusting the pore former level. These results suggest that the TPNs are promising pH-sensitive nanoparticulate pore formers in EC-coated dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

PubMed

Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

2004-12-01

Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

Statistical optimization and fabrication of a press coated pulsatile dosage form to treat nocturnal acid breakthrough.

PubMed

Agarwal, Vaibhav; Bansal, Mayank

2013-08-01

Present work focuses on the use of mimosa seed gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Mimosa pudica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 3(2) full factorial design was used in designing the experiment.% weight ratio of mimosa gum to hydroxy propyl methyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time and the cumulative % drug release in 360 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert(®) deciphered response which were in close proximity with the experimental responses, thus confirming the robustness as well as accuracy of the predicted model for the utilization of natural polymer like mimosa seed gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Oral controlled release optimization of pellets prepared by extrusion-spheronization processing.

PubMed

Bianchini, R; Vecchio, C

1989-06-01

Controlled release high dosage forms of a typical drug such as Indobufen were prepared as multiple-unit doses by employing extrusion-spheronization processing and subsequently film coating operations. The effects of drug particle size, drug/binder ratio, extruder screen size and preparation reproducibility on the physical properties of the spherical granules were evaluated. Controlled release optimization was obtained on the same granules by coating with polymeric membranes of different thickness consisting of water-soluble and insoluble substances. Film coating was applied from an organic solution using pan coating technique. The drug diffusion is allowed by dissolution of part of the membrane leaving small channels of the polymer coat. Further preparations were conducted to evaluate coatings applied from aqueous dispersion (pseudolatex) using air suspension coating technique. In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The most promising preparations having the desired in vitro release, were metered into hard capsules to obtain the drug unit dosage. Accelerated stability tests were carried out to assess the influence of time and the other storage parameters on the drug release profile.

Printing medicines as orodispersible dosage forms: Effect of substrate on the printed micro-structure.

PubMed

Planchette, C; Pichler, H; Wimmer-Teubenbacher, M; Gruber, M; Gruber-Woelfler, H; Mohr, S; Tetyczka, C; Hsiao, W-K; Paudel, A; Roblegg, E; Khinast, J

2016-07-25

We present our recent advancements in developing a viable manufacturing process for printed medicine. Our approach involves using a non-contact printing system that incorporates both piezoelectric- and solenoid valve-based inkjet printing technologies, to deliver both active and inactive pharmaceutical materials onto medical-graded orodispersible films. By using two complimentary inkjet technologies, we were able to dispense an extensive range of fluids, from aqueous drug solutions to viscous polymer coating materials. Essentially, we demonstrate printing of a wide range of formulations for patient-ready, orodispersible drug dosage forms, without the risk of drug degradation by ink heating and of substrate damages (by contact printing). In addition, our printing process has been optimized to ensure that the drug doses can be loaded onto the orally dissolvable films without introducing defects, such as holes or tears, while retaining a smooth surface texture that promotes patient adherence and allows for uniform post-coatings. Results show that our platform technology can address key issues in manufacturing orodispersible drug dosage forms and bring us closer to delivering personalized and precision medicine to targeted patient populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Low gloss UV-cured coatings for aircraft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowman, Mark; Muschar, Harry

A method of applying a low gloss coating to a substrate such as the exterior surface of an aircraft is disclosed. The coating composition comprising a polyene, a polythiol, a flatting agent and a coloring pigment is applied to the substrate and given a first dosage of UV radiation followed by a second dosage in which the second dosage is greater than the first resulting in an ultralow gloss coating.

Stability of dry coated solid dosage forms.

PubMed

Kablitz, Caroline Désirée; Urbanetz, Nora Anne

2009-01-01

The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage.

Bioavailability and in vivo release behavior of controlled-release multiple-unit theophylline dosage forms in beagle dogs, cynomolgus monkeys, and göttingen minipigs.

PubMed

Ikegami, Kengo; Tagawa, Kozo; Osawa, Takashi

2006-09-01

To determine the usefulness of monkey as an animal model, bioavailability and in vivo release behaviors of theophylline (TP) after oral administration of controlled-release beads in dogs, monkeys, and minipigs were evaluated. Controlled-release beads were prepared using a centrifugal-fluid type granulator, that is, CF-granulator, and Ethylcellulose (EC) was used as controlled-release coating agent. Aqueous solution and EC-coated beads, which contained TP were orally administered to animals after at least 1-week intervals. In dogs and minipigs, their relative bioavailabilities of EC-coated beads were 33.1% and 47.0%, respectively, and in vivo TP release from EC-coated beads in the gastrointestinal tract of dogs and minipigs were not reflected in vitro data. In monkeys, relative bioavailability of EC-coated beads was 80.0% and the highest among the three species, and release amount of TP from EC-coated beads at 24 h after oral administration was 82.8% and 92.4%, which was almost correlated to in vitro data. Therefore, the discrepancy of the relative bioavailability in three species is considered to be due to the difference of in vivo release behavior of TP. The monkey may be useful animal model for bioavailability studies of controlled-release dosage forms of TP from the viewpoint of in vitro-in vivo release correlation. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

PAT-tools for process control in pharmaceutical film coating applications.

PubMed

Knop, Klaus; Kleinebudde, Peter

2013-12-05

Recent development of analytical techniques to monitor the coating process of pharmaceutical solid dosage forms such as pellets and tablets are described. The progress from off- or at-line measurements to on- or in-line applications is shown for the spectroscopic methods near infrared (NIR) and Raman spectroscopy as well as for terahertz pulsed imaging (TPI) and image analysis. The common goal of all these methods is to control or at least to monitor the coating process and/or to estimate the coating end point through timely measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

An evaluation of the adhesion of solid oral dosage form coatings to the oesophagus.

PubMed

Smart, John D; Dunkley, Sian; Tsibouklis, John; Young, Simon

2015-12-30

There is a requirement for the development of oral dosage forms that are adhesive and allow extended oesophageal residence time for localised therapies, or are non-adhesive for ease of swallowing. This study provides an initial assessment of the in vitro oesophageal retention characteristics of several widely utilised pharmaceutical coating materials. To this end, a previously described apparatus has been used to measure the force required to pull a coated disc-shaped model tablet across a section of excised oesophageal tissue. Of the materials tested, the well-studied mucoadhesive polymer sodium alginate was found to be associated with significant oesophageal adhesion properties that was capable of 'self-repairing'. Hydroxypropylmethylcellulose exhibited less pronounced bioadhesive behaviour and blending this with plasticiser or with low molecular weight polymers and surfactants did not significantly affect this. Low molecular weight water soluble polymers, were found to behave similarly to the uncoated glass control disc. Polysorbates exhibited bioadhesion behaviour that was majorly influenced by the nature of the surfactant. The insoluble polymer ethylcellulose, and the relatively lipophilic surfactant sorbitan monooleate were seen to move more readily than the uncoated disc, suggesting that these may have a role as 'easy-to-swallow' coatings. Copyright © 2015 Elsevier B.V. All rights reserved.

Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.

PubMed

Thelen, Kirstin; Coboeken, Katrin; Willmann, Stefan; Dressman, Jennifer B; Lippert, Jörg

2012-03-01

The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design. Copyright © 2011 Wiley Periodicals, Inc.

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

PubMed

Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

2016-12-01

Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2  > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

PubMed

Leane, Michael M; Sinclair, Wayne; Qian, Feng; Haddadin, Raja; Brown, Alan; Tobyn, Mike; Dennis, Andrew B

2013-01-01

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant. A marked difference in physical stability of tablets was seen with the different fillers with microcrystalline cellulose (MCC) giving the best stability profile. It was found that minimising the number of compression steps led to improved formulation stability with a direct compression process giving the best results. Increased levels of crystallinity were seen in coated tablets most likely due to the exposure of the amorphous matrix to moisture and heat during the coating process. DSIMS analysis of the SDD particles indicated increased levels of polymer on the surface.

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.

PubMed

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.

Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer.

PubMed

Lecomte, F; Siepmann, J; Walther, M; MacRae, R J; Bodmeier, R

2004-09-14

The aim of this study was to investigate the importance of the type of plasticizer in polymer blends used for the coating of solid dosage forms, comparing a lipophilic and a hydrophilic plasticizer (dibutyl sebacate (DBS) and triethyl citrate (TEC)). In vitro drug release from propranolol hydrochloride (propranolol HCl)-loaded pellets coated with blends of ethyl cellulose (EC) and Eudragit L (100:0, 75:25, 50:50, 25:75 and 0:100 w/w) was investigated at low as well as at high pH. To better understand the underlying mass transport mechanisms, the physicochemical properties of the film coatings (e.g. mechanical resistance, water uptake and dry weight loss behavior) were determined. Interestingly, drug release strongly depended on the type of plasticizer. Importantly, not only the slope but also the shape of the release curves was affected, indicating that the chemical nature of the plasticizer plays a major role for the underlying drug release mechanisms. Diffusion through the intact polymer coatings and/or through water-filled cracks was found to be dominating for the control of drug release. The relative importance of these pathways strongly depended on the polymer blend ratio and type of plasticizer. In contrast to DBS, TEC rapidly leached out of the coatings, resulting in decreasing mechanical resistances of the films and, thus, facilitated crack formation. In addition, the hydrophilicity of the plasticizer significantly affected the water uptake behavior of the film coatings and, hence, changes in the coatings' toughness and drug permeability. Also the relative affinity of the plasticizer to the different polymers was found to be of significance. In contrast to TEC, DBS has a higher affinity to EC than to Eudragit L, resulting in potential redistributions of this plasticizer within the polymeric systems and changes in the release profiles during storage. Importantly, these effects could be avoided with appropriate curing conditions and preparation techniques for the coating dispersions.

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

PubMed

Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

2018-06-14

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging.

PubMed

Winner, Taryn L; Lanzarotta, Adam; Sommer, André J

2016-06-01

An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 μm.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection.

PubMed

Albrecht, K; Greindl, M; Kremser, C; Wolf, C; Debbage, P; Bernkop-Schnürch, A

2006-09-28

The aim of this study was to compare different oral delivery systems based on the thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for the validity of the hypothesis that unhydrated polymers provide better mucoadhesion in vivo. To achieve dry polymer application, a new, experimental dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been developed. Magnetic resonance imaging was used to localize the point of release of the thiolated polymer from the application forms via the positive magnetic resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was determined by ascertaining the residence time of the fluorescence-tagged thiomer on intestinal mucosa after 3 h. Results showed that in comparison to conventional application forms the Eutex capsules led to 1.9-fold higher mucoadhesive properties of PCP-Cys when compared to application with a conventional enteric-coated capsule, and to 1.4-fold higher mucoadhesion when compared to administration with an enteric-coated tablet of the thiomer. The findings of this study should contribute to the understanding of mucoadhesion and mucoadhesion influencing parameters in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

21 CFR 1308.33 - Exemption of certain anabolic steroid products; application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

21 CFR 1308.33 - Exemption of certain anabolic steroid products; application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

21 CFR 1308.33 - Exemption of certain anabolic steroid products; application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

21 CFR 1308.33 - Exemption of certain anabolic steroid products; application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exemption of certain anabolic steroid products; application. 1308.33 Section 1308.33 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE... of the dosage form, such as shape, color, coating, and scoring; (8) The label and labeling of the...

Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.

PubMed

Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen

2008-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.

Microneedle Coating Techniques for Transdermal Drug Delivery

PubMed Central

Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

2015-01-01

Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID:26556364

The effect of intestinal bacteria adherence on drug diffusion through solid films under stationary conditions.

PubMed

Rubinstein, A; Radai, R; Friedman, M; Fischer, P; Rokem, J S

1997-04-01

To study the in vitro and in vivo the role of surface bacterial adhesion on the diffusion of model drugs at stationary conditions. Salicylic acid (SA) diffusion through ethyl cellulose (EC) films was measured in vitro in side-by-side diffusion cells with and without E. coli of intestinal origin. Insulin (I) release from paper strips coated or uncoated with pectin films, with or without antibiotic treatment, was measured in vivo in conscious rats after cecal implantation by comparing blood glucose levels at Tmax of the pharmacodynamic effect. During five hours of diffusion studies which were performed immediately following incubation of EC films with bacteria, the diffusion rate of SA throughout the films was 2.72-fold lower in the presence of bacteria compared with the diffusion rate in the control studies conducted without bacteria. The mean blood glucose levels dropped in the rat to 40.6 +/- 21.6% of glucose basal levels within 2.4 +/- 1.4 h when uncoated I solid carriers were used. Glucose levels did not change for pectin-coated dosage forms. After antibiotic treatment which prevented the formation of bacterial biofilm on the surface of the I solid dosage forms, blood glucose levels dropped to 22.0 +/- 4.7% and 50.9 +/- 20.5% of glucose basal levels within 7.4 +/- 2.6 h and 1.8 +/- 0.9 h for pectin uncoated or coated dosage forms, respectively. Maximum bacterial adherence occurred at stationary conditions (RPM = 0), while at maximum agitation (200 RPM), almost no adherence occurred. (a) Bacterial adherence shows down the diffusion rate of SA through EC films; (b) Under stationary conditions bacterial adherence may also interfere with drug release from biodegradable (pectin) films; (c) Successful functioning of biodegradable colon-specific delivery systems depends on agitation and surface friction in the lumen of the colon.

Electrostatic powder coating: Principles and pharmaceutical applications.

PubMed

Prasad, Leena Kumari; McGinity, James W; Williams, Robert O

2016-05-30

A majority of pharmaceutical powders are insulating materials that have a tendency to accumulate charge. This phenomenon has contributed to safety hazards and issues during powder handling and processing. However, increased understanding of this occurrence has led to greater understanding and control of processing and product performance. More recently, the charging of pharmaceutical powders has been employed to adopt electrostatic powder coating as a pharmaceutical process. Electrostatic powder coating is a mature technology used in the finishing industry and much of that knowledge applies to its use in pharmaceutical applications. This review will serve to summarize the principles of electrostatic powder coating and highlight some of the research conducted on its use for the preparation of pharmaceutical dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

PubMed

Moghimipour, Eskandar; Rezaei, Mohsen; Kouchak, Maryam; Fatahiasl, Jafar; Angali, Kambiz Ahmadi; Ramezani, Zahra; Amini, Mohsen; Dorkoosh, Farid Abedin; Handali, Somayeh

2018-05-01

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

The Dynamic Characteristics of Silver Nanoparticles in Physiological Fluids: Toxicological Implications

DTIC Science & Technology

2014-11-19

and polysaccharide (Ag-PS) coated silver NM. As inhalation is a common route of exposure, an alveolar macrophage cell model with deposition dosages... polysaccharide -coated (Ag− PS) silver NMs. As inhalation is a common route of exposure, an alveolar macrophage cell model with deposition dosages...bioeffects, we evaluated fluid-specific influences on 25 nm Ag NPs with either a hydrocarbon or polysaccharide coating. Our data demonstrated that

X-ray powder diffractometry of intact film coated tablets--an approach to monitor the physical form of the active pharmaceutical ingredient during processing and storage.

PubMed

Yamada, Hiroyuki; Suryanarayanan, Raj

2007-08-01

The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD patterns of the tablets, containing each form of the active pharmaceutical ingredient (API), revealed at least one peak unique to each form. A semiquantitative microdiffractometric method was developed to nondestructively characterize the physical form of the API in intact film-coated tablets. This was accomplished even though the weight fraction of the API was <0.2 and that of mannitol, a highly crystalline excipient, was approximately 0.6. The method was used to determine the effect of aqueous film-coating process on the physical form of the API. The final dosage form was also monitored following storage at 40 degrees C/75% RH for 6 months. There was no phase transformation of the API either due to the film-coating process or following accelerated storage. This technique has potential utility not only for process control during manufacture, but also for the quality control of the final product. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

[Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

PubMed

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

2012-01-01

Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase. Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

PubMed

Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

2015-12-30

The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

Contamination of semi-solid dosage forms by leachables from aluminium tubes.

PubMed

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

2008-11-01

The objective of this study was to determine to what extent bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE) and its derivatives are extractable from epoxy-based coatings of aluminium tubes for pharmaceutical use and to monitor their leaching into different kinds of semi-solid dosage forms. Migration increasing factors should be evaluated. Extraction tests using acetonitrile for 10 days at 40 degrees C turned out to be suitable to estimate the maximum amount of extractables. A plain variability in the nature and amount of extractables among tubes of different vendors (n=7) could be demonstrated. Leaching of the remnants into various semi-solid drug products (ointment, cream, gel) during storage (30 degrees C/40 degrees C) was verifiable. Leachable profiles were, apart from storage time and temperature, decisively influenced by the matrix. In particular, matrix polarity seemed to play a crucial role. Thus, the highest amount of leachables was found in isopropanol-based carbomer gel. Furthermore, in-use conditions (mechanical stress) enhanced migration significantly. In order to ensure quality and safety of semi-solid formulae, interactions between the coating material and the drug product should be thoroughly evaluated.

Influence of Aggregate Coated with Modified Sulfur on the Properties of Cement Concrete

PubMed Central

Lee, Swoo-Heon; Hong, Ki-Nam; Park, Jae-Kyu; Ko, Jung

2014-01-01

This paper proposes the mixing design of concrete having modified sulfur-coated aggregate (MSCA) to enhance the durability of Portland cement concrete. The mechanical properties and durability of the proposed MSCA concrete were evaluated experimentally. Melting-modified sulfur was mixed with aggregate in order to coat the aggregate surface at a speed of 20 rpm for 120 s. The MSCA with modified sulfur corresponding to 5% of the cement weight did not significantly affect the flexural strength in a prism concrete beam specimen, regardless of the water-cement ratio (W/C). However, a dosage of more than 7.5% decreased the flexural strength. On the other hand, the MSCA considerably improved the resistance to the sulfuric acid and the freezing-thawing, regardless of the sulfur dosage in the MSCA. The coating modified sulfur of 5% dosage consequently led to good results for the mechanical properties and durability of MSCA concrete. PMID:28788703

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

PubMed

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.

Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.

PubMed

Young, Christopher R; Dietzsch, Caroline; Cerea, Matteo; Farrell, Thomas; Fegely, Kurt A; Rajabi-Siahboomi, Ali; McGinity, James W

2005-09-14

The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.

Industrial Applications of Terahertz Imaging

NASA Astrophysics Data System (ADS)

Zeitler, J. Axel; Shen, Yao-Chun

This chapter gives a concise overview of potential industrial applications for terahertz imaging that have been reported over the past decade with a discussion of the major advantages and limitations of each approach. In the second half of the chapter we discuss in more detail how terahertz imaging can be used to investigate the microstructure of pharmaceutical dosage forms. A particular focus in this context is the nondestructive measurement of the coating thickness of polymer coated tablets, both by means of high resolution offline imaging in research and development as well as for in-line quality control during production.

Use of proteins to minimize the physical aging of EUDRAGIT sustained release films.

PubMed

Kucera, Shawn A; McGinity, James W; Zheng, Weijia; Shah, Navnit H; Malick, A Waseem; Infeld, Martin H

2007-07-01

The objective of this study was to investigate the influence of two proteins, albumin and type B gelatin, on the physical aging of EUDRAGIT RS 30 D and RL 30 D coated theophylline pellets. The physicomechanical properties of sprayed films, thermal properties of cast films, influence of proteins on the zeta potential and particle size of the dispersion, and the release of proteins from cast films under simulated dissolution conditions were investigated. The release rate of theophylline decreased significantly over time from pellets coated with an acrylic dispersion containing 10% albumin when there was no acidification of the acrylic dispersion; however, when pellets were coated with an acidified EUDRAGIT/albumin dispersion, the theophylline release rate was stable for dosage forms stored in the absence of humidity. The drug release rate was faster for pellets coated with acrylic dispersions containing 10% gelatin compared to the albumin-containing formulations. When sprayed films were stored at 40 degrees C/75% RH, the water vapor permeability decreased significantly for both EUDRAGIT films and those containing EUDRAGIT and albumin; however, there was no significant change in this parameter when 10% gelatin was present. Albumin was released from the acrylic films when the pH of the dissolution media was below the isoelectric point of the protein while no quantitative release of gelatin was observed in pH 1.2 or 7.4 media. The effect of gelatin to prevent the decrease in drug release rate was due to stabilization in water vapor permeability of the film. Acidification of the polymeric dispersion resulted in electrostatic repulsive forces between albumin and the acrylic polymer, which stabilized the drug release rate when the dosage forms were stored in aluminum induction sealed containers at both 40 degrees C/75% RH and 25 degrees C/60% RH.

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms.

PubMed

Zhu, Yucun; Mehta, Ketan A; McGinity, James W

2006-01-01

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.

Surface modification of acetaminophen particles by atomic layer deposition.

PubMed

Kääriäinen, Tommi O; Kemell, Marianna; Vehkamäki, Marko; Kääriäinen, Marja-Leena; Correia, Alexandra; Santos, Hélder A; Bimbo, Luis M; Hirvonen, Jouni; Hoppu, Pekka; George, Steven M; Cameron, David C; Ritala, Mikko; Leskelä, Markku

2017-06-15

Active pharmaceutical ingredients (APIs) are predominantly organic solid powders. Due to their bulk properties many APIs require processing to improve pharmaceutical formulation and manufacturing in the preparation for various drug dosage forms. Improved powder flow and protection of the APIs are often anticipated characteristics in pharmaceutical manufacturing. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD, utilizing common chemistries for Al 2 O 3 , TiO 2 and ZnO, is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating process and maintains its stable polymorphic structure. Acetaminophen with nanometer scale ALD coatings shows slowed drug release. ALD TiO 2 coated acetaminophen particles show cytocompatibility whereas those coated with thicker ZnO coatings exhibit the most cytotoxicity among the ALD materials under study when assessed in vitro by their effect on intestinal Caco-2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Terahertz Technology: A Boon to Tablet Analysis

PubMed Central

Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.

2009-01-01

The terahertz gap has a frequency ranges from ∼0.3 THz to ∼10 THz in the electromagnetic spectrum which is in between microwave and infrared. The terahertz radiations are invisible to naked eye. In comparison with x-ray they are intrinsically safe, non-destructive and non-invasive. Terahertz spectroscopy enables 3D imaging of structures and materials, and the measurement of the unique spectral fingerprints of chemical and physical forms. Terahertz radiations are produced by a dendrimer based high power terahertz source and spectroscopy technologies. It resolves many of the questions left unanswered by complementary techniques, such as optical imaging, Raman and infrared spectra. In the pharmaceutical industries it enables nondestructive, internal, chemical analysis of tablets, capsules, and other dosage forms. Tablet coatings are a major factor in drug bioavailability. Therefore tablet coatings integrity and uniformity are of crucial importance to quality. Terahertz imaging gives an unparalleled certainty about the integrity of tablet coatings and the matrix performance of tablet cores. This article demonstrates the potential of terahertz pulse imaging for the analysis of tablet coating thickness by illustrating the technique on tablets. PMID:20490288

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

PubMed

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.

Physical aging in pharmaceutical polymers and the effect on solid oral dosage form stability.

PubMed

Kucera, Shawn A; Felton, Linda A; McGinity, James W

2013-12-05

The application of a polymeric film to a solid oral dosage form can be an effective technique to modify drug release. Most polymers used for such purposes are amorphous in nature and are subject to physical aging. This physical aging phenomenon has been shown to cause changes not only in the mechanical and drug release properties of polymeric films, but also the permeability of these films due to a densification and decrease in free volume of the polymer as the material relaxes to an equilibrated thermodynamic state. Temperature, humidity, and additional excipients in the coating formulations have been shown to influence the aging process. This review article discusses the process of physical aging in films prepared from aqueous dispersions, describes various analytical techniques that can be used to investigate the aging process, and highlights strategies to prevent such aging. Copyright © 2013 Elsevier B.V. All rights reserved.

Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

PubMed

Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

2016-05-01

This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

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

PubMed

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.

Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 1: In vitro approach using particle interaction methods.

PubMed

Drumond, Nélio; Stegemann, Sven

2018-05-01

Solid oral dosage forms (SODF) are drug vehicles commonly prescribed by physicists in primary and secondary cares, as they are the most convenient for the patient and facilitate therapy management. Concerns regarding unintended adhesion of SODF during oro-esophageal transit remain, especially in multimorbid patients, bedridden patients and patients suffering from dysphagia. Hence, this factor should be considered during the development of SODF, and more attention should be given on the design of appropriate surface conditions considering patients with swallowing problems. The aim of this work was to estimate the low mucoadhesion strength of different pharmaceutical polymers frequently used in coating technologies, since this property is thought to have impact on the mucoadhesive profile of SODF during oro-esophageal transit. In an approach using in vitro methods based on particle interactions, polyethylene glycol grades (PEG) showed the lowest interaction forces suggesting a more favorable in vivo performance than hydroxypropyl methylcellulose (HPMC), which was found to have the highest particle interaction. Preference should be given to coating formulations with lower concentrations of polymer and grades with low molecular weight. In addition, rheological measurements should be adopted when targeting poor mucoadhesive polymers. Copyright © 2018 Elsevier B.V. All rights reserved.

Feasibility of Raman spectroscopy as PAT tool in active coating.

PubMed

Müller, Joshua; Knop, Klaus; Thies, Jochen; Uerpmann, Carsten; Kleinebudde, Peter

2010-02-01

Active coating is a specific application of film coating where the active ingredient is comprised in the coating layer. This implementation is a challenging operation regarding the achievement of desired amount of coating and coating uniformity. To guarantee the quality of such dosage forms it is desirable to develop a tool that is able to monitor the coating operation and detect the end of the process. Coating experiments were performed at which the model drug diprophylline is coated in a pan coater on placebo tablets and tablets containing the active ingredient itself. During the active coating Raman spectra were recorded in-line. The spectral measurements were correlated with the average weight gain and the amount of coated active ingredient at each time point. The developed chemometric model was tested by monitoring further coated batches. Furthermore, the effects of pan rotation speed and working distance on the acquired Raman signal and, hence, resulting effect of the chemometric model were examined. Besides coating on placebo cores it was possible to determine the amount of active ingredient in the film when coated onto cores containing the same active ingredient. In addition, the method is even applicable when varying the process parameters and measurement conditions within a restricted range. Raman spectroscopy is an appropriate process analytical technology too.

Glass frits coated with silver nanoparticles for silicon solar cells

NASA Astrophysics Data System (ADS)

Li, Yingfen; Gan, Weiping; Zhou, Jian; Li, Biyuan

2015-06-01

Glass frits coated with silver nanoparticles were prepared by electroless plating. Gum Arabic (GA) was used as the activating agent of glass frits without the assistance of stannous chloride or palladium chloride. The silver-coated glass frits prepared with different GA dosages were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA). The characterization results indicated that silver-coated glass frits had the structures of both glass and silver. Spherical silver nanoparticles were distributed on the glass frits evenly. The density and particle size of silver nanoparticles on the glass frits can be controlled by adjusting the GA dosage. The silver-coated glass frits were applied to silver pastes to act as both the densification promoter and silver crystallite formation aid in the silver electrodes. The prepared silver-coated glass frits can improve the photovoltaic performances of solar cells.

RADIATION STERILIZATION OF COCOA POWDERS. Report No. 5 (Final), February 17, 1959-February 16, 1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeBenedictis, M.E.

1962-10-31

Results of studies on the effects of various dosages of gamma radiation upon the blooming characteristics and flavor of chocolate coatings, cocoa, and chocolate syrup showed that dosage levels that produce satisfactory results for controlling microorganisms in cocoas, cocoa butters, and chocolate coatings result in the development of off-flavors. No off-flavors were detected in chocolate syrups with a low fat content. (C.H.)

Development and characterization of crosslinked hyaluronic acid polymeric films for use in coating processes.

PubMed

Sgorla, Débora; Almeida, Andreia; Azevedo, Claudia; Bunhak, Ÿlcio Jose; Sarmento, Bruno; Cavalcanti, Osvaldo Albuquerque

2016-09-10

The aim of this work was to develop and characterize new hyaluronic acid-based responsive materials for film coating of solid dosage forms. Crosslinking of hyaluronic acid with trisodium trimetaphosphate was performed under controlled alkaline aqueous environment. The films were produced through casting process by mixing crosslinked or bare biopolymer in aqueous dispersion of ethylcellulose, at different proportions. Films were further characterized regarding morphology by scanning electron microscopy, robustness by permeation to water vapor transmission, and ability to hydrate in simulated gastric and intestinal physiological fluids. The safety and biocompatibility of films were assessed against Caco-2 and HT29-MTX intestinal cells. The permeation to water vapor transmission was favored by increasing hyaluronic acid content in the final formulation. When in simulated gastric fluid, films exhibited lower hydration ability compared to more extensive hydration in simulated intestinal fluids. Simultaneously, in simulated intestinal fluids, films partially lost weight, revealing ability for preventing drug release at gastric pH, but tailoring the release at higher intestinal pH. The physiochemical characterization suggests thermal stability of films and physical interaction between compounds of formulation. Lastly, cytotoxicity tests demonstrated that films and individual components of the formulations, when incubated for 4h, were safe for intestinal cells Overall, these evidences suggest that hyaluronic acid-based responsive films, applied as coating material of oral solid dosage forms, can prevent the premature release of drugs in harsh stomach conditions, but control the release it in gastrointestinal tract distal portion, assuring safety to intestinal mucosa. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of coating material on the flowability and dissolution of dry-coated fine ibuprofen powders.

PubMed

Qu, Li; Zhou, Qi Tony; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Morton, David A V

2015-10-12

This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation and performance evaluation of epoxy-based heat reflective coating for the pavement

NASA Astrophysics Data System (ADS)

Hu, B.; Liang, Y. H.; Guo, L. Y.; Jiang, T.

2017-04-01

According to the basic characteristics and composition of heat-reflective coating, combining with the functional requirements of road materials, the experiment selects the epoxy resin with good wear resistance and adhesive force as a film forming material, with TiO2, SiO2 and extinction powder as the main functional filler. The experiment gets a good formula with suitable viscosity, low glossiness and good cooling effect, optimizes by orthogonal experiment. The experiment evaluates the indoor and outdoor cooling effect of heat-reflective coating, and analyses the road performance of the coating. The results shows that the better heat-reflective coating formula included 12% of titanium dioxide, 4% of silica and 4% of extinction powder. When the dosage of coating is 0.8kg/m2, the indoor specimen of heat-reflective coating decrease the temperature of 12 ˜ 14°C, and the specimen under solar radiation can reduce the temperature of 7 ˜ 9°C. The pavement of heat-reflective coating has good wear resistance, but the road slip resistance partly declines. Therefore, it needs to add the anti-sliding particles to meet the safe driving requirements.

Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation.

PubMed

Lin, Hungyen; Dong, Yue; Shen, Yaochun; Zeitler, J Axel

2015-10-01

Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30-200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

Preformulation considerations for controlled release dosage forms. Part II. Selected candidate support.

PubMed

Chrzanowski, Frank

2008-01-01

Practical examples of preformulation support of the form selected for formulation development are provided using several drug substances (DSs). The examples include determination of the solubilities vs. pH particularly for the range pH 1 to 8 because of its relationship to gastrointestinal (GI) conditions and dissolution method development. The advantages of equilibrium solubility and trial solubility methods are described. The equilibrium method is related to detecting polymorphism and the trial solubility method, to simplifying difficult solubility problems. An example of two polymorphs existing in mixtures of DS is presented in which one of the forms is very unstable. Accelerating stability studies are used in conjunction with HPLC and quantitative X-ray powder diffraction (QXRD) to demonstrate the differences in chemical and polymorphic stabilities. The results from two model excipient compatibility methods are compared to determine which has better predictive accuracy for room temperature stability. A DSC (calorimetric) method and an isothermal stress with quantitative analysis (ISQA) method that simulates wet granulation conditions were compared using a 2 year room temperature sample set as reference. An example of a pH stability profile for understanding stability and extrapolating stability to other environments is provided. The pH-stability of omeprazole and lansoprazole, which are extremely unstable in acidic and even mildly acidic conditions, are related to the formulation of delayed release dosage forms and the resolution of the problem associated with free carboxyl groups from the enteric coating polymers reacting with the DSs. Dissolution method requirements for CR dosage forms are discussed. The applicability of a modified disintegration time (DT) apparatus for supporting CR dosage form development of a pH sensitive DS at a specific pH such as duodenal pH 5.6 is related. This method is applicable for DSs such as peptides, proteins, enzymes and natural products where physical observation can be used in place of a difficult to perform analytical method, saving resources and providing rapid preformulation support.

Valsartan.

PubMed

Ardiana, Febry; Suciati; Indrayanto, Gunawan

2015-01-01

Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. Generally, valsartan is available as film-coated tablets. This review summarizes thermal analysis, spectroscopy characteristics (UV, IR, MS, and NMR), polymorphism forms, impurities, and related compounds of valsartan. The methods of analysis of valsartan in pharmaceutical dosage forms and in biological fluids using spectrophotometer, CE, TLC, and HPLC methods are discussed in details. Both official and nonofficial methods are described. It is recommended to use LC-MS method for analyzing valsartan in complex matrices such as biological fluids and herbal preparations; in this case, MRM is preferred than SIM method. © 2015 Elsevier Inc. All rights reserved.

Application of design of experiment for polyox and xanthan gum coated floating pulsatile delivery of sumatriptan succinate in migraine treatment.

PubMed

Jagdale, Swati C; Pawar, Chandrakala R

2014-01-01

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 3(2) experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm(2), and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study.

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

PubMed

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.

Solution Coating of Pharmaceutical Nanothin Films and Multilayer Nanocomposites with Controlled Morphology and Polymorphism.

PubMed

Horstman, Elizabeth M; Kafle, Prapti; Zhang, Fengjiao; Zhang, Yifu; Kenis, Paul J A; Diao, Ying

2018-03-28

Nanosizing is rapidly emerging as an alternative approach to enhance solubility and thus the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Although numerous techniques have been developed to perform nanosizing of API crystals, precise control and modulation of their size in an energy and material efficient manner remains challenging. In this study, we present meniscus-guided solution coating as a new technique to produce pharmaceutical thin films of nanoscale thickness with controlled morphology. We demonstrate control of aspirin film thickness over more than 2 orders of magnitude, from 30 nm to 1.5 μm. By varying simple process parameters such as the coating speed and the solution concentration, the aspirin film morphology can also be modulated by accessing different coating regimes, namely the evaporation regime and the Landau-Levich regime. Using ellipticine-a poorly water-soluble anticancer drug-as another model compound, we discovered a new polymorph kinetically trapped during solution coating. Furthermore, the polymorphic outcome can be controlled by varying coating conditions. We further performed layer-by-layer coating of multilayer nanocomposites, with alternating thin films of ellipticine and a biocompatible polymer, which demonstrate the potential of additive manufacturing of multidrug-personalized dosage forms using this approach.

Layered lipid microcapsules for mesalazine delayed-release in children.

PubMed

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

2011-12-15

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

Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography.

PubMed

Markl, Daniel; Wahl, Patrick; Pichler, Heinz; Sacher, Stephan; Khinast, Johannes G

2018-01-30

This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets. Copyright © 2017. Published by Elsevier B.V.

QUANTITATIVE ULTRAVIOLET SPECTROSCOPY IN WEATHERING OF A MODEL POLYESTER-URETHANE COATING. (R828081E01)

EPA Science Inventory

Spectroscopy was used to quantify the effects of ultraviolet light on a model polyester–urethane coating as it degraded in an accelerated exposure chamber. An explorative calculation of the effective dosage absorbed by the coatings was made and, depending on the quantum...

Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation

PubMed Central

Lin, Hungyen; Dong, Yue; Shen, Yaochun; Zeitler, J Axel

2015-01-01

Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30–200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3377–3385, 2015 PMID:26284354

Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation.

PubMed

Lin, Hungyen; Dong, Yue; Shen, Yaochun; Axel Zeitler, J

2015-10-01

Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30-200μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3377-3385, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

PubMed

Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

2010-09-01

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

Application of Design of Experiment for Polyox and Xanthan Gum Coated Floating Pulsatile Delivery of Sumatriptan Succinate in Migraine Treatment

PubMed Central

Jagdale, Swati C.; Pawar, Chandrakala R.

2014-01-01

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 32 experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study. PMID:25530963

[Formulation and special investigations of innovative intraoral solid dosage forms.

PubMed

Kristo, K; kATONA, B; Piukovics, P; Olah, I; Sipos, B; Sipos, S E; Sovany, T; Hodi, K; Ifi Regdon, G

During our work, we summarized the types of solid dosage forms which were in the focus of attention in the last years because of their innovative pharmaceutical technology solution and simple use. The biopharmaceutics of solid dosage forms for intraoral use and the advantages of the use of these dosages forms were presented in general. However, these dosage forms cannot always be prepared with conventional pharmaceutical processes, therefore the special pharmaceutical solutions which can be applied for their preparation were presented. In addition to testing the European Pharmacopoeia dosage forms, the special tests which can be applied for the characterization of innovative solid dosage forms were highlighted.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

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

PubMed

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.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Comparative static curing versus dynamic curing on tablet coating structures.

PubMed

Gendre, Claire; Genty, Muriel; Fayard, Barbara; Tfayli, Ali; Boiret, Mathieu; Lecoq, Olivier; Baron, Michel; Chaminade, Pierre; Péan, Jean Manuel

2013-09-10

Curing is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-coating structures of dynamically cured tablets. Dynamic curing end-point was efficiently determined after 4h. The aim of the present work was to elucidate the influence of curing conditions on film-coating structures. Results demonstrated that 24h of static curing and 4h of dynamic curing, both performed at 60°C and ambient relative humidity, led to similar coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the coating layer. Interestingly, this new study clearly provided further knowledge into film-coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Changing the calculus of pediatric product development: narrowing the too-big gap between need and solution in a small market.

PubMed

Campbell, Sarah

2015-01-01

First, Deliece Hofen drops the pill into hot water to soften the outside coating. Then, she slices through the center of the pill with an X-ACTO knife and squeezes the isotretinoin inside into a syringe. With the drug in liquid form, she can now administer it to her ten-year-old son Brandon. ?The problem is...some of [the isotretinoin] is still left inside of the capsule and I?m not getting an exact dosage,? admits Hofen.

The effect of different coating materials on the prevention of powder bounce in the next generation impactor

PubMed Central

Khalili, Shadi Farshbaf; Ghanbarzadeh, Saeed; Nokhodchi, Ali; Hamishehkar, Hamed

2018-01-01

In the process of quality control of pulmonary drug delivery products, aerosolization efficiency is mainly determined using impactors, e.g. next generation impactor (NGI). However, particle bounce may interfere with the validity and accuracy of results due to the overestimation of the respirable fraction. It is suggested that the coating of impactor's stages may prevent the particle bounce. Therefore, coating materials may influence the results of the aerosolization indexes of pulmonary dosage forms. The aim of this study was to investigate if the aerosolization indices are affected differently by using the different coating materials. In this study, the effects of using different materials including Span® 85, Tween® 80, silicon® oil, glycerin and Brij® 35/glycerin mixture recommended for the coating of NGI stages on the aerosolization indices such as fine particle fraction, fine particle dose, mass median aerodynamic diameter, and geometric standard deviation of salbutamol emitted from a commercial metered dose inhaler (MDI), were assessed. Three statistically different results were obtained on using Tween® 80, Span® 85 and silicon oil, and glycerin and Brij®35/glycerin mixture. It can be concluded that the type of coating material influenced the aerosolization indices of the examined MDI in NGIs. PMID:29853937

The effect of different coating materials on the prevention of powder bounce in the next generation impactor.

PubMed

Khalili, Shadi Farshbaf; Ghanbarzadeh, Saeed; Nokhodchi, Ali; Hamishehkar, Hamed

2018-06-01

In the process of quality control of pulmonary drug delivery products, aerosolization efficiency is mainly determined using impactors, e.g. next generation impactor (NGI). However, particle bounce may interfere with the validity and accuracy of results due to the overestimation of the respirable fraction. It is suggested that the coating of impactor's stages may prevent the particle bounce. Therefore, coating materials may influence the results of the aerosolization indexes of pulmonary dosage forms. The aim of this study was to investigate if the aerosolization indices are affected differently by using the different coating materials. In this study, the effects of using different materials including Span ® 85, Tween ® 80, silicon ® oil, glycerin and Brij ® 35/glycerin mixture recommended for the coating of NGI stages on the aerosolization indices such as fine particle fraction, fine particle dose, mass median aerodynamic diameter, and geometric standard deviation of salbutamol emitted from a commercial metered dose inhaler (MDI), were assessed. Three statistically different results were obtained on using Tween ® 80, Span ® 85 and silicon oil, and glycerin and Brij ® 35/glycerin mixture. It can be concluded that the type of coating material influenced the aerosolization indices of the examined MDI in NGIs.

Innovations in coating technology.

PubMed

Behzadi, Sharareh S; Toegel, Stefan; Viernstein, Helmut

2008-01-01

Despite representing one of the oldest pharmaceutical techniques, coating of dosage forms is still frequently used in pharmaceutical manufacturing. The aims of coating range from simply masking the taste or odour of drugs to the sophisticated controlling of site and rate of drug release. The high expectations for different coating technologies have required great efforts regarding the development of reproducible and controllable production processes. Basically, improvements in coating methods have focused on particle movement, spraying systems, and air and energy transport. Thereby, homogeneous distribution of coating material and increased drying efficiency should be accomplished in order to achieve high end product quality. Moreover, given the claim of the FDA to design the end product quality already during the manufacturing process (Quality by Design), the development of analytical methods for the analysis, management and control of coating processes has attracted special attention during recent years. The present review focuses on recent patents claiming improvements in pharmaceutical coating technology and intends to first familiarize the reader with the available procedures and to subsequently explain the application of different analytical tools. Aiming to structure this comprehensive field, coating technologies are primarily divided into pan and fluidized bed coating methods. Regarding pan coating procedures, pans rotating around inclined, horizontal and vertical axes are reviewed separately. On the other hand, fluidized bed technologies are subdivided into those involving fluidized and spouted beds. Then, continuous processing techniques and improvements in spraying systems are discussed in dedicated chapters. Finally, currently used analytical methods for the understanding and management of coating processes are reviewed in detail in the last section of the review.

[Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

PubMed

Watanabe, Yoshiteru; Mukai, Baku; Kawamura, Ken-ichi; Ishikawa, Tatsuya; Namiki, Michihiro; Utoguchi, Naoki; Fujii, Makiko

2002-02-01

In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p < 0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in Cmax and area under the plasma theophylline concentration-time curve (AUC0-->24) between the press-coated tablet and aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.

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

Code of Federal Regulations, 2010 CFR

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. ...

[Levitra (oral dispersible tablet)--an innovative drug for the treatment of patients with erectile dysfunction].

PubMed

Korneev, I A

2013-01-01

The arsenal of professionals providing assistance to men with erectile dysfunction includes a new, mouth dissolving dosage form of the vardenafil--levitra ODT. This form is effective, safe, and has a higher bioavailability as compared to vardenafil in the form of coated tablets. POTENT I and POTENT II studies revealed that levitra ODT equally successfully corrects erectile dysfunction in men younger and older than 65 years regardless of concomitant diseases and metabolic disorders: hypertension, diabetes, dyslipidemia. In addition, it was found that this drug helped to successfully carry out sexual intercourse in the first 15 minutes after dosing in 62.5% of patients. This allows to widely recommend levitra ODT for the treatment of erectile dysfunction in young men and older men.

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

Code of Federal Regulations, 2010 CFR

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. ...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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. ...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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. ...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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. ...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 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...

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast.

PubMed

Schug, B S; Brendel, E; Chantraine, E; Wolf, D; Martin, W; Schall, R; Blume, H H

2002-06-01

The aim of this study was to investigate the effect of concomitant food intake on the bioavailability of two nifedipine containing modified release dosage forms for once daily administration. The clinical study was performed to investigate the in vivo relevance of pH-dependent differences in the in vitro release properties of the two dosage forms. This was a randomized, open, 4-way crossover study in 24 healthy, male subjects. Following an overnight fast of 12 h single doses of Adalat OROS or Slofedipine XL were administered either in the fasted state or immediately after a high fat American breakfast. Nifedipine plasma concentrations in samples obtained until 48 h after drug administration were determined using a validated LC-MS/MS method. Calculation of pharmacokinetic parameters was conducted model-independently. The two dosage forms as well as the two administration conditions were compared by calculating point estimates and 90% confidence intervals for the relevant pharmacokinetic parameters. In vitro dissolution tests were performed using a paddle apparatus 3 acc. USP, a pharmacopoeial dissolution system consisting of reciprocating cylinders in flat-bottomed glass vessels, with various buffer systems covering the entire physiological pH-range of the gastrointestinal tract. After fasted administration the extent of bioavailability of nifedipine as characterized by AUC(0,infinity) was slightly lower for Slofedipine XL compared with Adalat OROS with a point estimate of 82.3% primarily resulting from pronounced differences in nifedipine concentrations during the first 15 h after administration. Accordingly, maximum plasma concentrations were lower after administration of Slofedipine XL compared with Adalat OROS (point estimate: 84.3%). Under fed conditions the differences in bioavailability between the two products as characterized by the pharmacokinetic parameters AUC(0,tn) and Cmax were greater than after fasting conditions with point estimates of 69.6% and 81.0%, respectively. However, most striking was a pronounced delay in nifedipine absorption observed under fed conditions after administration of Slofedipine XL which resulted in lag-times of more than 15 h in 15 out of 24 subjects. Owing to this lag-time under fed conditions the relative bioavailability of nifedipine from Slofedipine XL compared with Adalat OROS was only 28% over the intended dosing interval of 24 h. In this study a dosage form-dependent food interaction was observed which, under fed conditions, resulted in pronounced differences in the relative bioavailability of nifedipine between Slofedipine XL and Adalat OROS over the intended dosing interval of 24 h. The delay in nifedipine absorption when Slofedipine XL is administered after a high-fat breakfast may be explained by the formulation properties. Slofedipine XL is an erosive tablet with an acid resistant coating whereas Adalat OROS is designed with an osmotic push-pull system. Under fed conditions drug from the single unit enteric coated dosage form exhibits a delayed absorption probably due to an extensively prolonged gastric residence time which does not allow drug release, on the other hand the osmotically driven push-pull system is not sensitive to concomitant food intake. The observed phenomenon might be of therapeutic relevance. For example a change from taking Slofedipine XL in the fed to the fasted state might result in increased systemic concentrations of nifedipine.

Orodispersible films: Product transfer from lab-scale to continuous manufacturing.

PubMed

Thabet, Yasmin; Breitkreutz, Joerg

2018-01-15

Orodispersible films have been described as new beneficial dosage forms for special patient populations. Due to various production settings, different requirements on film formulations are required for non- continuous and continuous manufacturing. In this study, a continuous coating machine was qualified in regards of the process conditions for film compositions and their effects on the formed films. To investigate differences between both manufacturing processes, various film formulations of hydrochlorothiazide and hydroxypropylcellulose (HPC) or hydroxypropylmethycellulose (HPMC) as film formers were produced and the resulting films were characterized. The qualification of the continuously operating coating machine reveals no uniform heat distribution during drying. Coating solutions for continuous manufacturing should provide at least a dynamic viscosity of 1 Pa*s (wet film thickness of 500 μm, velocity of 15.9 cm/min). HPC films contain higher residuals of ethanol or acetone in bench-scale than in continuous production mode. Continuous production lead to lower drug content of the films. All continuously produced films disintegrate within less than 30 s. There are observed significant effects of the production process on the film characteristics. When transferring film manufacturing from lab-scale to continuous mode, film compositions, processing conditions and suitable characterization methods have to be carefully selected and adopted. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental analysis of tablet properties for discrete element modeling of an active coating process.

PubMed

Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

2013-03-01

Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.

In line NIR quantification of film thickness on pharmaceutical pellets during a fluid bed coating process.

PubMed

Lee, Min-Jeong; Seo, Da-Young; Lee, Hea-Eun; Wang, In-Chun; Kim, Woo-Sik; Jeong, Myung-Yung; Choi, Guang J

2011-01-17

Along with the risk-based approach, process analytical technology (PAT) has emerged as one of the key elements to fully implement QbD (quality-by-design). Near-infrared (NIR) spectroscopy has been extensively applied as an in-line/on-line analytical tool in biomedical and chemical industries. In this study, the film thickness on pharmaceutical pellets was examined for quantification using in-line NIR spectroscopy during a fluid-bed coating process. A precise monitoring of coating thickness and its prediction with a suitable control strategy is crucial to the quality assurance of solid dosage forms including dissolution characteristics. Pellets of a test formulation were manufactured and coated in a fluid-bed by spraying a hydroxypropyl methylcellulose (HPMC) coating solution. NIR spectra were acquired via a fiber-optic probe during the coating process, followed by multivariate analysis utilizing partial least squares (PLS) calibration models. The actual coating thickness of pellets was measured by two separate methods, confocal laser scanning microscopy (CLSM) and laser diffraction particle size analysis (LD-PSA). Both characterization methods gave superb correlation results, and all determination coefficient (R(2)) values exceeded 0.995. In addition, a prediction coating experiment for 70min demonstrated that the end-point can be accurately designated via NIR in-line monitoring with appropriate calibration models. In conclusion, our approach combining in-line NIR monitoring with CLSM and LD-PSA can be applied as an effective PAT tool for fluid-bed pellet coating processes. Copyright © 2010 Elsevier B.V. All rights reserved.

Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders.

PubMed

Malamatari, Maria; Somavarapu, Satyanarayana; Taylor, Kevin M G; Buckton, Graham

2016-01-01

Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of nanosuspensions to solid oral and inhalable dosage forms minimises the physical instability associated with their liquid state, enhances patient compliance and enables targeted oral and pulmonary drug delivery. This review outlines solidification methods for nanosuspensions. It includes spray and freeze drying as the most widely used techniques. Fluidised-bed coating, granulation and pelletisation are also discussed as they yield nanocrystalline formulations with more straightforward downstream processing to tablets or capsules. Spray-freeze drying, aerosol flow reactor and printing of nanosuspensions are also presented as promising alternative solidification techniques. Results regarding the solid state, in vitro dissolution and/or aerosolisation efficiency of the nanocrystalline formulations are given and combined with available in vivo data. Focus is placed on the redispersibility of the solid nanocrystalline formulations, which is a prerequisite for their clinical application. A few solidified nanocrystalline products are already on the market and many more are in development. Oral and inhalable nanoparticle formulations are expected to have great potential especially in the areas of personalised medicine and delivery of high drug doses (e.g. antibiotics) to the lungs, respectively.

A study on the applicability of in-line measurements in the monitoring of the pellet coating process.

PubMed

Hudovornik, Grega; Korasa, Klemen; Vrečer, Franc

2015-07-30

Special populations including paediatric and elderly patients often need advanced approaches in treatment, such as one-a-day dosing, which is achieved with modified release formulations or alternative routes of applications such as nasogastric route. Pellets are a dosage form that is frequently used in such formulations. The aim of the present work was to study the applicability of two in-line techniques, namely, Near Infrared Spectroscopy (NIR) and Spatial Filtering Technique (SFT) in the pellet coating process. The first objective of our work was to develop a prediction model for moisture content determination with the in-line NIR and to test its robustness in terms of sensitivity to changes in composition of the pellets and performance in wide range of moisture content. Secondly, the in-line SFT measurement was correlated with different off-line particle size methods. The third objective was to evaluate the ability of both in-line techniques for the detection of undesired deviations during the process, such as pellet attrition and agglomeration. Finally, the ability to predict coating thickness with the in-line NIR probe was evaluated. Results suggested that NIR prediction model for moisture content was less robust outside the calibration range and was also sensitive to changes in composition of the film coating. Nevertheless, satisfactory prediction was achieved in the case when coating composition was partially altered and adequate calibration range was used. The SFT probe results were in good correlation with off-line particle size measurement methods and proved to be an effective tool for coating thickness determination during the coating, however, the probe failed to accurately show the actual amount of the agglomerates formed during the process. In experiment when pellet attrition was initiated, both probes successfully detected abrasion of the pellet surface in real time. Furthermore, a predictive NIR model for coating thickness was made and showed a good potential to measure coating thickness in-line, suggesting that the NIR probe can be used as a single tool to monitor water content, coating thickness, and deviations in the coating process. Copyright © 2015 Elsevier B.V. All rights reserved.

Gastric emptying of enteric-coated tablets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, H.M.; Chernish, S.M.; Rosenek, B.D.

1984-03-01

To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effectmore » in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets.« less

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

PubMed

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.

Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection.

PubMed

Bear, Joseph C; Patrick, P Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J; Pankhurst, Quentin A; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P; Mayes, Andrew G

2016-09-27

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it's drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

PubMed

Weitschies, Werner; Blume, Henning; Mönnikes, Hubert

2010-01-01

Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract. Copyright 2009 Elsevier B.V. All rights reserved.

Development of the rectal dosage form with silver-coated glass beads for local-action applications in lower sections of the gastrointestinal tract.

PubMed

Siczek, Krzysztof; Fichna, Jakub; Zatorski, Hubert; Karolewicz, Bożena; Klimek, Leszek; Owczarek, Artur

2018-03-01

Recent findings indicating the anti-inflammatory action of silver preparations through modulation of the gut microbiota and apoptosis of inflammatory cells predestine silver use in inflammatory bowel disease (IBD). The aim of our study was to validate the possibility of effective silver release from silver-coated glass beads for anti-inflammatory local application in the lower sections of the gastrointestinal (GI) tract. Silver-coated glass beads were prepared using magnetron method. Release of silver from the silver-coated glass bead surface was carried out in BIO-DIS reciprocating cylinder apparatus. Erosion of silver coating and indirect estimation of the silver release dynamics was assessed using scanning electron microscope. Rectal suppositories containing silver-coated glass beads were prepared using five different methods (M1-M5) and X-ray scanned for their composition. The XR microanalysis and the chemical composition analysis evidenced for a rapid (within 30 min) release of nearly 50% of silver from the coating of the glass beads, which remained stable up to 24 h of incubation. The most homogeneous distribution of beads in the entire volume of the suppository was obtained for formulation M5, where the molten base was poured into mold placed in an ice bath, and the beads were added after 10 s. Our study is the first to present the concept of enclosing silver-coated glass beads in the lipophilic suppository base to attenuate inflammation in the lower GI tract and promises efficient treatment with reduced side effects.

Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

PubMed

Wulff, R; Rappen, G-M; Koziolek, M; Garbacz, G; Leopold, C S

2015-09-18

The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Code of Federal Regulations, 2010 CFR

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. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

In-vitro Drug Dissolution Studies in Medicinal Compounds.

PubMed

Bozal-Palabiyik, Burcin; Uslu, Bengi; Ozkan, Yalcin; Ozkan, Sibel A

2018-03-22

After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

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.

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

[Pharmaceutical advice concerning different pharmaceutical dosage forms].

PubMed

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.

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Code of Federal Regulations, 2010 CFR

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. ...

Melt-processed polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2015-12-28

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

Soft gelatin capsules (softgels).

PubMed

Gullapalli, Rampurna Prasad

2010-10-01

It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.

Application of terahertz pulse imaging as PAT tool for non-destructive evaluation of film-coated tablets under different manufacturing conditions.

PubMed

Dohi, Masafumi; Momose, Wataru; Yoshino, Hiroyuki; Hara, Yuko; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Terada, Katsuhide

2016-02-05

Film-coated tablets (FCTs) are a popular solid dosage form in pharmaceutical industry. Manufacturing conditions during the film-coating process affect the properties of the film layer, which might result in critical quality problems. Here, we analyzed the properties of the film layer using a non-destructive approach with terahertz pulsed imaging (TPI). Hydrophilic tablets that become distended upon water absorption were used as core tablets and coated with film under different manufacturing conditions. TPI-derived parameters such as film thickness (FT), film surface reflectance (FSR), and interface density difference (IDD) between the film layer and core tablet were affected by manufacturing conditions and influenced critical quality attributes of FCTs. Relative standard deviation of FSR within tablets correlated well with surface roughness. Tensile strength could be predicted in a non-destructive manner using the multivariate regression equation to estimate the core tablet density by film layer density and IDD. The absolute value of IDD (Lateral) correlated with the risk of cracking on the lateral film layer when stored in a high-humidity environment. Further, in-process control was proposed for this value during the film-coating process, which will enable a feedback control system to be applied to process parameters and reduced risk of cracking without a stability test. Copyright © 2015 Elsevier B.V. All rights reserved.

Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

PubMed Central

Zhang, Qilei; Gladden, Lynn F.; Avalle, Paolo; Zeitler, J. Axel; Mantle, Michael D.

2013-01-01

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescol® XL) when stored under accelerated conditions (40 °C/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescol® XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor f1 and a “similarity” factor f2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance. PMID:24300564

Interdiction of hypoglycemia in diabetic children by multiparticulate dosage form with controlled glucose release.

PubMed

Franc, Aleš; Sabadková, Dana; Neumann, David; Pavloková, Sylvie; Kopecká, Pavlína; Muselík, Jan

2016-11-01

Patients tend to evade the occurrence of hypoglycemic episodes by excessive carbohydrate intake. Glucose pellets with delayed release in the time of the maximum effect of insulin can not only prevent hypoglycemia but also eliminate the preventive carbohydrate intake. The pellets can be administered in a mixture with semisolid food. The cores containing glucose in combination with osmotically active agents (croscarmellose sodium, carmellose sodium, polyethylene glycol, or carboxymethyl starch) were prepared by extrusion-spheronization and coated with 15% water ethylcellulose dispersion (Surelease® B NF) in Wurster column (Medipo, Havlíčkův Brod, Czech Republic) into four coating levels (12.5, 25, 35, and 50%). Mean particle size is 0.63-0.73 for cores and 0.82-0.98 for coated pellets. Cores and coated pellets have excellent or good flow properties according to Hausner ratio and Carr index. Aspect ratio ranges from 1.78 to 2.17 for cores and from 1.73 to 2.31 for coated pellets. Dissolution was performed using pH-independent method and method with continual change of pH. The suitable pH-independent release was achieved in the samples containing carboxymethyl starch or polyethylene glycol. Glucose release is enabled by a membrane rupture caused by core swelling. It can be, therefore, assumed that the glucose release profile will not be affected by food or transit time.

Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

PubMed

Bendas, Ehab R; Christensen, J Mark; Ayres, James W

2010-04-01

The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

The impact of space travel on dosage form design and use.

PubMed

Aronsohn, A; Brazeau, G; Hughes, J

1999-07-01

The author speculates on potential factors that may influence the utilization of dosage forms in space. A key assumption is that most of the arguments will be based on current understanding of how dosage forms work on earth. Factors discussed include dosage form stability; and administration of drugs, particularly inhalation and aerosols. A sample experiment used a tissue culture model of drug transfer for passively absorbed drugs to address how alterations in hydrostatic pressure would change paracellular transport.

Physicochemical interactions in solid dosage forms.

PubMed

Narang, Ajit S; Desai, Divyakant; Badawy, Sherif

2012-10-01

Complete characterization and mechanistic understanding of physicochemical interactions in solid dosage forms are not only important for consistent manufacturability, stability, and bioavailability of the drug product, but are also expected under the quality-by-design paradigm of drug development. Lack of this understanding can impact successful and timely development, scale-up, and commercial manufacture of dosage forms. This article highlights the stability and bioavailability implications of physicochemical interactions in dosage forms citing a couple of examples where such interactions necessitated the recall of commercial drug products.

Over-the-counter pharmaceuticals: exploratory research of consumer preference toward solid oral dosage forms.

PubMed

Reisenwitz, T H; Wimbish, G J

1996-01-01

The capsule dosage form in nonprescription pharmaceuticals persists as being one of the most vulnerable to product tampering. This study examines consumer preference toward three solid oral dosage forms (capsules, caplets, and tablets) in nonprescription products. Thirteen independent variables representing dosage form attributes are measured on semantic differential scales. The data are analyzed using analysis of variance (ANOVA) and factor analysis. Implications for the pharmaceutical marketer are noted. Future directions for research are also outlined.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 1: Surface and Cross-Sectional Chemical Analysis.

PubMed

Dereymaker, Aswin; Scurr, David J; Steer, Elisabeth D; Roberts, Clive J; Van den Mooter, Guy

2017-04-03

Fluid bed coating has been shown to be a suitable manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug-polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In this study, fluid bed coating is proposed for the production of controlled release dosage forms of glass solutions by applying a second, rate controlling membrane on top of the glass solution. Adding a second coating layer adds to the physical and chemical complexity of the drug delivery system, so a thorough understanding of the physical structure and phase behavior of the different coating layers is needed. This study aimed to investigate the surface and cross-sectional characteristics (employing scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (ToF-SIMS)) of an indomethacin-polyvinylpyrrolidone (PVP) glass solution, top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) were also considered. In addition, polymer miscibility and the phase analysis of the underlying glass solution were investigated. Significant differences in surface and cross-sectional topography of the different rate controlling membranes or the way they are applied (solution vs dispersion) were observed. These observations can be linked to the polymer miscibility differences. The presence of PVP was observed in all rate controlling membranes, even if it is not part of the coating solution. This could be attributed to residual powder presence in the coating chamber. The distribution of PVP among the sample surfaces depends on the concentration and the rate controlling polymer used. Differences can again be linked to polymer miscibility. Finally, it was shown that the underlying glass solution layer remains amorphous after coating of the rate controlling membrane, whether formed from an ethanol solution or an aqueous dispersion.

Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements.

PubMed

Zhang, Tingting; Stilwell, Jackie L; Gerion, Daniele; Ding, Lianghao; Elboudwarej, Omeed; Cooke, Patrick A; Gray, Joe W; Alivisatos, A Paul; Chen, Fanqing Frank

2006-04-01

Quantum dots (Qdots) are now used extensively for labeling in biomedical research, and this use is predicted to grow because of their many advantages over alternative labeling methods. Uncoated Qdots made of core/shell CdSe/ZnS are toxic to cells because of the release of Cd2+ ions into the cellular environment. This problem has been partially overcome by coating Qdots with polymers, poly(ethylene glycol) (PEG), or other inert molecules. The most promising coating to date, for reducing toxicity, appears to be PEG. When PEG-coated silanized Qdots (PEG-silane-Qdots) are used to treat cells, toxicity is not observed, even at dosages above 10-20 nM, a concentration inducing death when cells are treated with polymer or mercaptoacid coated Qdots. Because of the importance of Qdots in current and future biomedical and clinical applications, we believe it is essential to more completely understand and verify this negative global response from cells treated with PEG-silane-Qdots. Consequently, we examined the molecular and cellular response of cells treated with two different dosages of PEG-silane-Qdots. Human fibroblasts were exposed to 8 and 80 nM of these Qdots, and both phenotypic as well as whole genome expression measurements were made. PEG-silane-Qdots did not induce any statistically significant cell cycle changes and minimal apoptosis/necrosis in lung fibroblasts (IMR-90) as measured by high content image analysis, regardless of the treatment dosage. A slight increase in apoptosis/necrosis was observed in treated human skin fibroblasts (HSF-42) at both the low and the high dosages. We performed genome-wide expression array analysis of HSF-42 exposed to doses 8 and 80 nM to link the global cell response to a molecular and genetic phenotype. We used a gene array containing approximately 22,000 total probe sets, containing 18,400 probe sets from known genes. Only approximately 50 genes (approximately 0.2% of all the genes tested) exhibited a statistically significant change in expression level of greater than 2-fold. Genes activated in treated cells included those involved in carbohydrate binding, intracellular vesicle formation, and cellular response to stress. Conversely, PEG-silane-Qdots induce a down-regulation of genes involved in controlling the M-phase progression of mitosis, spindle formation, and cytokinesis. Promoter analysis of these results reveals that expression changes may be attributed to the down-regulation of FOXM and BHLB2 transcription factors. Remarkably, PEG-silane-Qdots, unlike carbon nanotubes, do not activate genes indicative of a strong immune and inflammatory response or heavy-metal-related toxicity. The experimental evidence shows that CdSe/ZnS Qdots, if appropriately protected, induce negligible toxicity to the model cell system studied here, even when exposed to high dosages. This study indicates that PEG-coated silanized Qdots pose minimal impact to cells and are a very promising alternative to uncoated Qdots.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2010 CFR

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. ...

Chemical and pharmacological comparison of modern and traditional dosage forms of Joshanda.

PubMed

Parveen, Sajida; Irfan Bukhari, Nadeem; Shehzadi, Naureen; Qamar, Shaista; Ali, Ejaz; Naheed, Surriya; Latif, Abida; Yuchi, Alamgeer; Hussain, Khalid

2017-12-11

Recently, a traditional remedy (Joshanda) has been replaced largely by modern ready-to-use dosage forms, which have not been compared to the original remedy. Therefore, the present study aimed to compare a number of modern dosage forms with traditional remedy. Seven brands, 3 batches each, were compared with a Lab-made formulation with reference to analytical (proximate analyses, spectroscopic and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory and antibacterial activities). Chemical and pharmacological differences were found between Lab-made Joshanda and modern dosage forms. Such variations were also found within the brands and batches of modern formulations (p < 0.05). The Lab-made Joshanda showed significantly higher pharmacological activities as compared to modern brands (p ). The results of the present study indicate that modern dosage forms are unstandardised and less effective than the traditional remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as reference to produce comparable dosage forms.

Dynamics of HIV neutralization by a microbicide formulation layer: biophysical fundamentals and transport theory.

PubMed

Geonnotti, Anthony R; Katz, David F

2006-09-15

Topical microbicides are an emerging HIV/AIDS prevention modality. Microbicide biofunctionality requires creation of a chemical-physical barrier against HIV transmission. Barrier effectiveness derives from properties of the active compound and its delivery system, but little is known about how these properties translate into microbicide functionality. We developed a mathematical model simulating biologically relevant transport and HIV-neutralization processes occurring when semen-borne virus interacts with a microbicide delivery vehicle coating epithelium. The model enables analysis of how vehicle-related variables, and anti-HIV compound characteristics, affect microbicide performance. Results suggest HIV neutralization is achievable with postcoital coating thicknesses approximately 100 mum. Increased microbicide concentration and potency hasten viral neutralization and diminish penetration of infectious virus through the coating layer. Durable vehicle structures that restrict viral diffusion could provide significant protection. Our findings demonstrate the need to pair potent active ingredients with well-engineered formulation vehicles, and highlight the importance of the dosage form in microbicide effectiveness. Microbicide formulations can function not only as drug delivery vehicles, but also as physical barriers to viral penetration. Total viral neutralization with 100-mum-thin coating layers supports future microbicide use against HIV transmission. This model can be used as a tool to analyze diverse factors that govern microbicide functionality.

Microphase separation in solid lipid dosage forms as the cause of drug release instability.

PubMed

Lopes, Diogo Gomes; Koutsamanis, Ioannis; Becker, Karin; Scheibelhofer, Otto; Laggner, Peter; Haack, Detlev; Stehr, Michael; Zimmer, Andreas; Salar-Behzadi, Sharareh

2017-01-30

Although lipid excipients are of increasing interest for development of taste-masked and modified release formulations, the drug release instability and the lack of mechanistic understanding in that regard still prevent their larger-scale application. In this work, we investigated the physical stability of a binary (tripalmitin/polysorbate 65) lipid coating formulation with a known stable polymorphism. The coating composition was characterized using DSC to construct the phase diagram of binary system and polarized light microscopy to display the microstructure organization. The water uptake and the erosion of slabs cast from the coating formulations were investigated post-production and after storage. Subsequently, N-acetylcysteine particles were coated with the selected formulations and the drug release stability was investigated. Additionally, microstructure characterization was performed via SEM and X-ray diffraction. The drug release instability was explained by polysorbate 65 and tripalmitin phase growth during storage, especially at 40°C, suggesting that polysorbate 65 can leak out of tripalmitin spherulitic structures, creating lipophilic and impermeable tripalmitin regions. The growth of polysorbate 65 phase leads to larger hydrophilic channels with reduced tortuosity. This work indicates that for obtaining stable drug release profiles from advanced lipid formulations, microphase separation should be prevented during storage. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease intended for colon-specific drug delivery.

PubMed

Freire, Cristina; Podczeck, Fridrun; Veiga, Francisco; Sousa, João

2010-02-01

Colon-specific delivery of drugs can be achieved with dosage forms coated with biopolymers that are metabolized selectively by the colonic microflora and yet resistant to enzymatic digestion in the small intestine. The aim of this study was to study the influence of formulation factors on the performance of mixed films from high-amylose starches and Surelease((R)), applied using a spray-coating process, as potential colon-specific delivery devices. 5-Aminosalicylic acid-loaded pellets were prepared by an extrusion-spheronization process and film coated with mixtures of the starches and Surelease((R)). Optimization of the coating formulation, that is, starch-to-Surelease((R)) ratio, film-coating thickness, and type of starch, was undertaken first in enzyme-free media resembling the conditions in the stomach and small intestine. The effect of curing of the film coating on the drug release profile upon storage was also evaluated. Optimized coating formulations were further assessed for enzymatic digestibility using artificial gastric and intestinal juices containing commercially available pepsin and pancreatin or alpha-amylase from hog pancreas, respectively. Finally, drug release was assessed in fluid-simulating conditions in the colon (SCF) containing Bacillus licheniformis alpha-amylase. Film coatings comprising high-amylose starches and Surelease((R)) in a ratio of 1:2 (w/w) and film thickness of approximately 45 microm were able to withstand the chemical and enzymatic environment of the upper gastrointestinal tract, in particular, resisted degradation by the pancreatic alpha-amylases. Stability of the coatings during storage was achieved with additional curing. In SCF, these coatings were susceptible to enzymatic degradation. This study showed that high amylose starch-mixed films can be successfully used as colon-specific delivery devices. The preparation of the coating dispersions described is simple and rapid, without the need to extract the amylose component of starch.

The transit of dosage forms through the small intestine.

PubMed

Yuen, Kah-Hay

2010-08-16

The human small intestine, with its enormous absorptive surface area, is invariably the principal site of drug absorption. Hence, the residence time of a dosage form in this part of the gut can have a great influence on the absorption of the contained drug. Various methods have been employed to monitor the gastrointestinal transit of pharmaceutical dosage forms, but the use of gamma-scintigraphy has superceded all the other methods. However, careful consideration of the time interval for image acquisition and proper analysis of the scintigraphic data are important for obtaining reliable results. Most studies reported the mean small intestinal transit time of various dosage forms to be about 3-4h, being closely similar to that of food and water. The value does not appear to be influenced by their physical state nor the presence of food, but the timing of food intake following administration of the dosage forms can influence the small intestinal transit time. While the mean small intestinal transit time is quite consistent among dosage forms and studies, individual values can vary widely. There are differing opinions regarding the effect of density and size of dosage forms on their small intestinal transit properties. Some common excipients employed in pharmaceutical formulations can affect the small intestinal transit and drug absorption. There is currently a lack of studies regarding the effects of excipients, as well as the timing of food intake on the small intestinal transit of dosage forms and drug absorption. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Coatings from blends of Eudragit® RL and L55: a novel approach in pH-controlled drug release.

PubMed

Wulff, R; Leopold, C S

2014-12-10

The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid-ethyl acrylate copolymers. Pellets were coated with blends of Eudragit(®) RL PO (RL) and Eudragit(®) L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of type and level of water-soluble additives on drug release and surface and mechanical properties of Surelease films.

PubMed

Rohera, Bhagwan D; Parikh, Nilesh H

2002-11-01

Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.

3D-micro-patterned fibrous dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-03-01

At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms. ...

21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

21 CFR 520.390 - Chloramphenicol oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 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 § 520.390...

21 CFR 520.445 - Chlortetracycline oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chlortetracycline oral dosage forms. 520.445 Section 520.445 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 § 520.445...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 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 § 520.540...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 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 § 520.540...

21 CFR 520.300 - Cambendazole oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 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 § 520.300...

21 CFR 520.300 - Cambendazole oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 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 § 520.300...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 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 § 520.540...

21 CFR 520.390 - Chloramphenicol oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 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 § 520.390...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 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 § 520.540...

21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 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 § 520.620...

21 CFR 520.390 - Chloramphenicol oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 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 § 520.390...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 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 § 520.540...

21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 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 § 520.620...

21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 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 § 520.620...

21 CFR 520.390 - Chloramphenicol oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 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 § 520.390...

21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 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 § 520.620...

21 CFR 520.445 - Chlortetracycline oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline oral dosage forms. 520.445 Section 520.445 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 § 520.445...

21 CFR 520.300 - Cambendazole oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 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 § 520.300...

21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 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 § 520.620...

21 CFR 520.300 - Cambendazole oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 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 § 520.300...

21 CFR 520.905 - Fenbendazole oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905...

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

Code of Federal Regulations, 2010 CFR

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...

21 CFR 522.1696 - Penicillin G procaine injectable dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1696 Penicillin G procaine injectable dosage forms. ...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Code of Federal Regulations, 2010 CFR

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...

Dynamic mechanical thermal analysis of hypromellose 2910 free films.

PubMed

Cespi, Marco; Bonacucina, Giulia; Mencarelli, Giovanna; Casettari, Luca; Palmieri, Giovanni Filippo

2011-10-01

It is common practice to coat oral solid dosage forms with polymeric materials for controlled release purposes or for practical and aesthetic reasons. Good knowledge of thermo-mechanical film properties or their variation as a function of polymer grade, type and amount of additives or preparation method is of prime importance in developing solid dosage forms. This work focused on the dynamic mechanical thermal characteristics of free films of hypromellose 2910 (also known as HPMC), prepared using three grades of this polymer from two different manufacturers, in order to assess whether polymer chain length or origin affects the mechanical or thermo-mechanical properties of the final films. Hypromellose free films were obtained by casting their aqueous solutions prepared at a specific concentrations in order to obtain the same viscosity for each. The films were stored at room temperature until dried and then examined using a dynamic mechanical analyser. The results of the frequency scans showed no significant differences in the mechanical moduli E' and E″ of the different samples when analysed at room temperature; however, the grade of the polymer affected material transitions during the heating process. Glass transition temperature, apparent activation energy and fragility parameters depended on polymer chain length, while the material brand showed little impact on film performance. Copyright © 2011 Elsevier B.V. All rights reserved.

Oral Medicines for Children in the European Paediatric Investigation Plans

PubMed Central

van Riet – Nales, Diana A.; Römkens, Erwin G. A. W.; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

2014-01-01

Introduction Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. Methods All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. Results A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. Conclusion The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound. PMID:24897509

Oral medicines for children in the European paediatric investigation plans.

PubMed

van Riet-Nales, Diana A; Römkens, Erwin G A W; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F A M; Egberts, Toine C G; Rademaker, Carin M A

2014-01-01

Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.

In Vitro Determination of Drug Transfer from Drug-Coated Balloons

PubMed Central

Seidlitz, Anne; Kotzan, Nadine; Nagel, Stefan; Reske, Thomas; Grabow, Niels; Harder, Claus; Petersen, Svea; Sternberg, Katrin; Weitschies, Werner

2013-01-01

Drug-coated balloons are medical devices designed to locally deliver drug to diseased segments of the vessel wall. For these dosage forms, drug transfer to the vessel wall needs to be examined in detail, since drug released into the blood is cleared from the site. In order to examine drug transfer, a new in vitro setup was developed combining the estimation of drug loss during advancement to the site of application in a model coronary artery pathway with a hydrogel compartment representing, as a very simplified model, the vessel wall. The transfer of fluorescent model substances as well as the drug paclitaxel from coated balloons to the simulated vessel wall was evaluated using this method. The model was suitable to quantify the fractions transferred to the hydrogel and also to qualitatively assess distribution patterns in the hydrogel film. In the case of fluorescein sodium, rhodamin b and paclitaxel, vast amounts of the coated substance were lost during the simulated passage and only very small fractions of about 1% of the total load were transferred to the gel. This must be attributed to good water solubility of the fluorescent substances and the mechanical instability of the paclitaxel coating. Transfer of the hydrophobic model substance triamterene was however nearly unaffected by the preliminary tracking procedure with transferred fractions ranging from 8% to 14%. Analysis of model substance distribution yielded inhomogeneous distributions indicating that the coating was not evenly distributed on the balloon surface and that a great fraction of the coating liquid did not penetrate the folds of the balloon. This finding is contradictory to the generally accepted assumption of a drug depot inside the folds and emphasizes the necessity to thoroughly characterize in vitro performance of drug-coated balloons to support the very promising clinical data. PMID:24391863

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

PubMed

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.

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 500.26 - Timed-release dosage form drugs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 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 § 520.622...

21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 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 § 520.622...

21 CFR 520.88 - Amoxicillin oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 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 § 520.88 Amoxicillin oral...

21 CFR 520.90 - Ampicillin oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 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 § 520.90 Ampicillin oral...

21 CFR 520.154 - Bacitracin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 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 § 520.154 Bacitracin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

21 CFR 520.88 - Amoxicillin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 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 § 520.88 Amoxicillin oral...

21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 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 § 520.763...

21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 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 § 520.82...

21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 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 § 520.622...

21 CFR 520.45 - Albendazole oral dosage forms.

Code of Federal Regulations, 2010 CFR

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...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 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 § 520.1044 Gentamicin...

21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 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 § 520.763...

21 CFR 520.45 - Albendazole oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 520.90 - Ampicillin oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 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 § 520.90 Ampicillin oral...

21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 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 § 520.82...

21 CFR 520.1120 - Haloxon oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Haloxon oral dosage forms. 520.1120 Section 520.1120 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 § 520.1120 Haloxon oral...

21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 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 § 520.763...

21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 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 § 520.622...

21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 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 § 520.82...

21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 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 § 520.763...

21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 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 § 520.763...

21 CFR 520.90 - Ampicillin oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 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 § 520.90 Ampicillin oral...

21 CFR 520.903 - Febantel oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Febantel oral dosage forms. 520.903 Section 520.903 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 § 520.903 Febantel oral...

21 CFR 520.88 - Amoxicillin oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 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 § 520.88 Amoxicillin oral...

21 CFR 520.38 - Albendazole oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Albendazole oral dosage forms. 520.38 Section 520.38 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 § 520.38 Albendazole oral...

21 CFR 520.90 - Ampicillin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 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 § 520.90 Ampicillin oral...

21 CFR 520.154 - Bacitracin oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 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 § 520.154 Bacitracin oral...

21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride oral dosage forms. 520.1242 Section 520.1242 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 § 520.1242...

21 CFR 520.154 - Bacitracin oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 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 § 520.154 Bacitracin oral...

21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 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 § 520.622...

21 CFR 520.154 - Bacitracin oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 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 § 520.154 Bacitracin oral...

21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 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 § 520.82...

21 CFR 520.88 - Amoxicillin oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 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 § 520.88 Amoxicillin oral...

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 520.1696 - Penicillin oral dosage forms.

Code of Federal Regulations, 2010 CFR

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...

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

PubMed

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.

Buccal Dosage Forms: General Considerations for Pediatric Patients.

PubMed

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.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry.

PubMed

Corá, Luciana A; Romeiro, Fernando G; Paixão, Fabiano C; Américo, Madileine F; Oliveira, Ricardo B; Baffa, Oswaldo; Miranda, José Ricardo A

2006-08-01

To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t50) was quantified from 50% increase of pixels in the imaging area. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t50) calculated for in vitro was 25+/-5 min and for in vivo was 13+/-5 min. In vivo also were determined mean values for GRT (55+/-19 min), SITT (185+/-82 min) and OCTT (240+/-88 min). AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

Oral drug delivery in personalized medicine: unmet needs and novel approaches.

PubMed

Wening, Klaus; Breitkreutz, Jörg

2011-02-14

Increasing knowledge into personalized medicine has demonstrated the need for individual dosing. Drug dosage forms are urgently needed enabling an individual therapy, especially for oral drug delivery. This review is focusing on approaches for solid and liquid oral dosage forms for individual dosing. The proposed dosage forms and devices may be distinguished into assembling and partition concepts and have been categorized regarding their applicability, costs, dose flexibility and potential benefits. Opportunities, challenges and further unmet needs are elaborated and critically discussed. Liquid dosage forms can be accurately dosed by novel dropping tubes or oral syringes, but less precisely by dosing spoons and cups. Breaking scored tablets into fragments show major risks such as inaccurate dosing, formation of potent dust and stability issues of the residual segments. Novel approaches are proposed for solid dosage forms enabling a flexible and appropriate therapy such as various dispensers for multiparticulate drug formulations. However, most of the proposals still have to prove their applicability in practice. Promising concepts are the solid dosage pen and drug-loaded oral films which can be cut in individual sections enabling freely selectable doses. Further research and development are required for novel dosage forms and medical devices appropriate for individualized therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

PubMed

Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

2015-01-01

Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

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

PubMed

Raijada, Dhara; Genina, Natalja; Fors, Daniela; Wisaeus, Erik; Peltonen, Jouko; Rantanen, Jukka; Sandler, Niklas

2013-10-01

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 printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing methods, and detection limit of analytical techniques for characterization of printed dosage forms are some of the concerns that need to be addressed for development of printable dosage forms of poorly soluble drugs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Plasma-assisted deposition of microcapsule containing Aloe vera extract for cosmeto-textiles

NASA Astrophysics Data System (ADS)

Nascimento do Carmo, S.; Zille, A.; Souto, A. P.

2017-10-01

Dielectric Barrier Discharge (DBD) atmospheric-pressure plasma was employed to enhance the deposition of commercial microcapsules (MCs) containing Aloe vera extract onto a cotton/polyester (50:50) fabric. DBD conditions were optimized in term of energy dosage and contact angle. The MCs were applied by padding and printing methods and the coatings were characterized in terms of SEM and FTIR. MCs display a spherical shape with size between 2 and 8 μm with an average wall thickness of 0.5 μm. The MCs applied by printing and pretreated with a plasma dosage of 1.6 kW m2 min-1 showed the best results with an increased adhesion of 200% and significant penetration of MCs into the fibres network. Plasma printed fabric retained 230% more MCs than untreated fabric after 10 washing cycles. However, the coating resistance between unwashed and washed samples was only improved by 5%. Considering the fact that no binder or crosslinking agents were used, the DBD plasma-assisted deposition of MCs revealed to be a promising environmental safe and low cost coating technology.

Advances in solid dosage form manufacturing technology.

PubMed

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.

Automatic identification and normalization of dosage forms in drug monographs

PubMed Central

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

Transit of pharmaceutical dosage forms through the small intestine.

PubMed Central

Davis, S S; Hardy, J G; Fara, J W

1986-01-01

The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract. PMID:3732895

Liquisolid technique: a promising alternative to conventional coating for improvement of drug photostability in solid dosage forms.

PubMed

Khames, Ahmed

2013-10-01

The objective of this study was to investigate the photoprotective effect of liquisolid technique on amlodipine, a calcium channel blocker antihypertensive drug, representing a photosensitive drug model. Several liquisolid formulations were prepared using propylene glycol as a water-miscible nonvolatile vehicle at drug/solvent ratio (1:1), Avicel PH 102 as a carrier, nanometer-sized amorphous silicon and titanium dioxide either alone or in combination as coating materials. The carrier/coat ratio (R) was varied from 5 to 50. The prepared liquisolids, coated, noncoated tablets and drug substance were irradiated with a light dose of 0.5 W/m(2)/h visible light, 55.1 W/m(2)/h UVA, and 0.247 W/m(2)/h UVB for 8 h. The effect of coating material type and (R) value on the drug dissolution rate and photostability was studied. Results were statistically analyzed by post hoc two-way ANOVA at a probability level (α = 0.05). The results indicated that liquisolid technique not only improved the dissolution rate, but also significantly inhibited the photodegradative effect of different light energies in all prepared liquisolid formulations. The residual drug percentage reached 97.37% in comparison to 73.8% for the drug substance after 8 h of irradiation. The residual drug percentage was affected by the (R) value. Statistically; the detected difference was significant at the selected probability level (α = 0.05). It can thus be concluded that this liquisolid technique is a promising alternative to conventional coating procedures in formulations containing photosensitive drugs.

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

PubMed

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

2011-04-01

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

Moisture sorption and permeability characteristics of polymer films: implications for their use as barrier coatings for solid dosage forms containing hydrolyzable drug substances.

PubMed

Mwesigwa, Enosh; Basit, Abdul W; Buckton, Graham

2008-10-01

Moisture sorption and permeability characteristics of polymer films were studied and their effectiveness to protect a hydrolyzable drug assessed. Cast films were prepared from Eudragit L30 D-55, Eudragit EPO, Opadry AMB and Sepifilm LP dispersions, which were also applied onto tablet cores formulated with aspirin as a model moisture sensitive active ingredient. Sorption studies were undertaken using dynamic vapour sorption, ranging between 0% and 90% RH at 25 degrees C. Cast films exhibited fast equilibration (

[Preparation of Coated CMC-Fe0 Using Rheological Phase Reaction Method and Research on Degradation of TCE in Water].

PubMed

Fan, Wen-jing; Cheng, Yue; Yu, Shu-zhen; Fan, Xiao-feng

2015-06-01

The coated nanoscale zero-valent iron (coated CMC-Fe0) was synthesized with cheap and environment friendly CMC as the coating agent using rheological phase reaction. The sample was characterized by means of XRD, SEM, TEM and N2 adsorption-stripping and used to study reductive dechlorination of TCE. The experimental results indicated that the removal rate of TCE was about 100% when the CMC-Fe0 dosage was 6 g x L(-1), the initial TCE concentration was 5 mg x L(-1) and the reaction time was 40 h. The TCE degradation reaction of coated CMC-Fe0 followed a pseudo-first-order kinetic model. Finally, the product could be simply recovered.

The effects of substrate size, surface area, and density on coat thickness of multi-particulate dosage forms.

PubMed

Heinicke, Grant; Matthews, Frank; Schwartz, Joseph B

2005-01-01

Drugs layering experiments were performed in a fluid bed fitted with a rotor granulator insert using diltiazem as a model drug. The drug was applied in various quantities to sugar spheres of different mesh sizes to give a series of drug-layered sugar spheres (cores) of different potency, size, and weight per particle. The drug presence lowered the bulk density of the cores in proportion to the quantity of added drug. Polymer coating of each core lot was performed in a fluid bed fitted with a Wurster insert. A series of polymer-coated cores (pellets) was removed from each coating experiment. The mean diameter of each core and each pellet sample was determined by image analysis. The rate of change of diameter on polymer addition was determined for each starting size of core and compared to calculated values. The core diameter was displaced from the line of best fit through the pellet diameter data. Cores of different potency with the same size distribution were made by layering increasing quantities of drug onto sugar spheres of decreasing mesh size. Equal quantities of polymer were applied to the same-sized core lots and coat thickness was measured. Weight/weight calculations predict equal coat thickness under these conditions, but measurable differences were found. Simple corrections to core charge weight in the Wurster insert were successfully used to manufacture pellets having the same coat thickness. The sensitivity of the image analysis technique in measuring particle size distributions (PSDs) was demonstrated by measuring a displacement in PSD after addition of 0.5% w/w talc to a pellet sample.

Bioequivalence Study of Warfarin in Healthy Chinese Volunteers With a Validated High-Performance Liquid Chromatography-Mass Spectrometry Method.

PubMed

Li, Wenlong; Bu, Fanlong; Li, Rong; Wang, Benjie; Shaikh, Abdul Sami; Zhang, Yunyun; Guo, Ruichen; Zhang, Rui

2018-03-01

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t ½ , 103.5 ± 18.8 and 105.8 ± 21.3 hours; T max , 0.7 ± 0.5 and 1.3 ± 0.8 hours; C max , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC 0∼360 , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL -1 ·h; AUC 0∼∞ , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL -1 ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin. © 2017, The American College of Clinical Pharmacology.

21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 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 § 520.1802 Piperazine-carbon disulfide comple...

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.

PubMed

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.

Novel delivery device for monolithical solid oral dosage forms for personalized medicine.

PubMed

Wening, Klaus; Breitkreutz, Jörg

2010-08-16

There is an evident need for solid oral dosage forms allowing patients' tailor-made dosing due to variations in metabolization or small therapeutic indexes of drug substances. The objective of this work is the development of a device equipped with a novel solid dosage form, containing carvedilol as model drug, for the delivery of monolithical drug carriers in individual doses. The device was developed and constructed enabling an exact feed rate and dose adjustment by a cutting mechanism. A twin-screw extruder was used for producing cylindrical solid dosage forms. Divided doses were characterized by mass variation, cutting behavior and drug dissolution in order to investigate their applicability for practical use. Different formulations could be extruded obtaining straight cylindrical rods, which are divisible in exact slices by using the novel device. Forces below 20 N were needed to divide doses which comply with pharmacopoeial specification "conformity of mass". The developed formulations exhibit a sustained release of carvedilol within a range from 7 up to 16 h. A novel system consisting of a device and a cylindrical dosage form was developed. Patients' individual doses can be applied as monolithical solid dosage forms for oral use.

Bioavailability of intranasal promethazine dosage forms in dogs

NASA Technical Reports Server (NTRS)

Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

1998-01-01

Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

Advanced stable lipid-based formulations for a patient-centric product design.

PubMed

Becker, Karin; Saurugger, Eva-Maria; Kienberger, Diana; Lopes, Diogo; Haack, Detlev; Köberle, Martin; Stehr, Michael; Lochmann, Dirk; Zimmer, Andreas; Salar-Behzadi, Sharareh

2016-01-30

Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process. The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65. A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable β-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release. This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

PubMed Central

Nath, Bipul; Nath, Lila Kanta

2013-01-01

The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985

The peculiar behavior of the glass transition temperature of amorphous drug-polymer films coated on inert sugar spheres.

PubMed

Dereymaker, Aswin; Van Den Mooter, Guy

2015-05-01

Fluid bed coating has been proposed in the past as an alternative technology for manufacturing of drug-polymer amorphous solid dispersions, or so-called glass solutions. It has the advantage of being a one-step process, and thus omitting separate drying steps, addition of excipients, or manipulation of the dosage form. In search of an adequate sample preparation method for modulated differential scanning calorimetry analysis of beads coated with glass solutions, glass transition broadening and decrease of the glass transition temperature (Tg ) were observed with increasing particle size of crushed coated beads and crushed isolated films of indomethacin (INDO) and polyvinylpyrrolidone (PVP). Substituting INDO with naproxen gave comparable results. When ketoconazole was probed or the solvent in INDO-PVP films was switched to dichloromethane (DCM) or a methanol-DCM mixture, two distinct Tg regions were observed. Small particle sizes had a glass transition in the high Tg region, and large particle sizes had a glass transition in the low Tg region. This particle size-dependent glass transition was ascribed to different residual solvent amounts in the bulk and at the surface of the particles. A correlation was observed between the deviation of the Tg from that calculated from the Gordon-Taylor equation and the amount of residual solvent at the Tg of particles with different sizes. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

76 FR 63304 - Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

...] Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug... entitled ``Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug Products for Anticounterfeiting.'' This guidance provides recommendations on design considerations for incorporating physical...

Dosage and Distribution in Morphosyntax Intervention: Current Evidence and Future Needs

ERIC Educational Resources Information Center

Proctor-Williams, Kerry

2009-01-01

This article reviews the effectiveness of dose forms and the efficacy of dosage and distribution in morphosyntax intervention for children. Dose forms include the commonly used techniques, procedures, and intervention contexts that constitute teaching episodes; dosage includes the quantitative measures of dose, dose frequency, total intervention…

Microbicide dosage forms.

PubMed

Rohan, L C; Devlin, B; Yang, H

2014-01-01

Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

PubMed

Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

2014-07-01

Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

Influence of additives on melt viscosity, surface tension, and film formation of dry powder coatings.

PubMed

Sauer, Dorothea; McGinity, James W

2009-06-01

Limited information on thermally cured dry-powder coatings used for solid dosage forms has been available in the literature. The aim of this study was to characterize the film formation process of Eudragit L 100-55 dry-powder coatings and to investigate the influence of film additives on melt viscosity and surface tension. The coating process employed no liquids and the plasticizer was combined with the polymer using hot melt extrusion. Thermoanalytical methods including differential scanning calorimetry and thermogravimetric analysis (TGA) were used to investigate the thermal properties of the dry-coating formulations. The rheological behavior of the coating formulations were characterized with the extrusion torque, and the surface energy parameters were determined from contact angle measurements. The influence of the level of triethyl citrate (TEC) as plasticizer and polyethylene glycol (PEG) 3350 in the polymer film on film formation was investigated using a digital force tester. TGA confirmed thermal stability of all coating excipients at the investigated curing conditions. Increasing TEC levels and the addition of PEG 3350 as a low melting excipient in the coating reduced the viscosity of the polymer. Plasticization of the polymer with TEC increased the surface free energy, whereas the admixture of 10% PEG 3350 did not affect the surface free energy of Eudragit L 100-55. The spreading coefficient of the polymers over two sample tablet formulations was reduced with increasing surface free energy. During the curing process, puncture strength, and elongation of powder-cast films increased. The effect of curing time on the mechanical properties was dependent on the plasticizer content. The incorporation of TEC and PEG 3350 into the Eudragit L 100-55 powder coating formulation improved film formation. Mechanical testing of powder-cast films showed an increase of both elongation and puncture strength over the curing process as criterion for polymer particle fusion, where film formation progressed faster at high plasticizer levels.

Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

PubMed

Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

2014-07-01

Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant.

PubMed

Tatavarti, Aditya; Kesisoglou, Filippos

2015-11-01

Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Multifunctional Delivery Systems for Advanced oral Uptake of Peptide/Protein Drugs.

PubMed

Park, Jin Woo; Kim, Sun Jin; Kwag, Dong Sup; Kim, Sol; Park, Jeyoung; Youn, Yu Seok; Bae, You Han; Lee, Eun Seong

2015-01-01

In recent years, advances in biotechnology and protein engineering have enabled the production of large quantities of proteins and peptides as important therapeutic agents. Various researchers have used biocompatible functional polymers to prepare oral dosage forms of proteins and peptides for chronic use and for easier administration to enhance patient compliance. However, there is a need to enhance their safety and effectiveness further. Most macromolecules undergo severe denaturation at low pH and enzymatic degradation in the gastrointestinal tract. The macromolecules' large molecular size and low lipophilicity cause low permeation through the intestinal membrane. The major strategies that have been used to overcome these challenges (in oral drug carrier systems) can be classified as follows: enteric coating or encapsulation with pH-sensitive polymers or mucoadhesive polymers, co-administration of protease inhibitors, incorporation of absorption enhancers, modification of the physicochemical properties of the macromolecules, and site-specific delivery to the colon. This review attempts to summarize the various advanced oral delivery carriers, including nanoparticles, lipid carriers, such as liposomes, nano-aggregates using amphiphilic polymers, complex coacervation of oppositely charged polyelectrolytes, and inorganic porous particles. The particles were formulated and/or surface modified with functional polysaccharides or synthetic polymers to improve oral bioavailability of proteins and peptides. We also discuss formulation strategies to overcome barriers, therapeutic efficacies in vivo, and potential benefits and issues for successful oral dosage forms of the proteins and peptides.

Fibrous dosage forms by wet 3D-micro-patterning: process design, manufacture, and drug release rate.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-06-19

Recently, we have introduced fibrous dosage forms prepared by 3D-micro-patterning of drug-laden viscous melts. Such dosage forms enable predictable microstructures and increased drug release rates, and they can be manufactured continuously. However, melt processing is not applicable if the melting temperature of the formulation is greater than the degradation temperature of the drug or of the excipient. In this work, therefore, a continuous wet micro-patterning process that operates at ambient temperature is presented. The excipient is plasticized by a solvent and the patterned dosage form is solidified by air drying. Process models show that the micro-patterning time is the ratio of the fiber length in the dosage form and the velocity of the fiber stream. It was 1.3 minutes in the experiments, but can be reduced further. The drying time is limited by the diffusive flux of solvent through the fibers: it was about 3 minutes for the experimental conditions. Furthermore, models are developed to illustrate the effects of fiber radius, inter-fiber spacing, viscosity of the drug-excipient-solvent mixture, and drying conditions on the microstructure of the dosage form. Models and experimental results show that for a viscosity of the wet fibers of the order 10 3 Pa·s, both the patterned microstructure is well preserved and the crossed fibers are well bonded. Finally, the drug release rate by the dosage forms is experimentally determined and theoretically modeled. The results of the experiments validate the models fairly. Copyright © 2018. Published by Elsevier B.V.

MRI as a tool for evaluation of oral controlled release dosage forms.

PubMed

Dorożyński, Przemysław P; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J

2012-02-01

The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (μCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

A nanohybrid system for taste masking of sildenafil.

PubMed

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

2012-01-01

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

A nanohybrid system for taste masking of sildenafil

PubMed Central

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

2012-01-01

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

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

PubMed

Karkossa, Frank; Klein, Sandra

2017-10-01

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

Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.

PubMed

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

Can lipid nanoparticles improve intestinal absorption?

PubMed

Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

2016-12-30

Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-07-15

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

Theoretical and experimental studies on silica-coated carbon spheres composites

NASA Astrophysics Data System (ADS)

Guo, Xingmei; Liu, Haixing; Shen, Yinghua; Niu, Mei; Yang, Yongzhen; Liu, Xuguang

2013-10-01

In order to prepare carbon-based photonic crystals, first of all, theoretical modeling calculation was used to predict the bandgap characteristics of silica-coated carbon spheres. Then, silica-coated carbon spheres composites were synthesized using tetraethyl orthosilicate as precursor of silica by a sol-gel method combined with Stöber method. Effect of reaction conditions on surface coating of carbon spheres with silica, including the pH, the amount of precursor and reaction time, was emphasized. The morphology and structure of the composites and the effect coating of carbon spheres with silica were characterized by field-emission scanning electron microscopy, high resolution transmission electron microscopy and Fourier-transform infrared spectrometry. The coating ratio of silica was investigated by thermogravimetry. The results show that pH value played an important role in coating reaction, the dosage of the precursor and reaction time had significant effect on coating layer thickness, that is, coating ratio. Carbon spheres coated with silica had good dispersibility and dispersion stability in water and ethanol, which is preconditions of reactivity of carbon spheres in liquid phase and lays the basis for the application of carbon spheres.

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

PubMed

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.

Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets.

PubMed

Korasa, Klemen; Hudovornik, Grega; Vrečer, Franc

2016-10-10

Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

A survey of caregivers of Nigerian children less than 6 years of age to determine the experience and perception of acceptability of oral solid dosage forms.

PubMed

Orubu, Samuel; Okwelogu, Chinyere; Opanuga, Olabisi; Tuleu, Catherine

2018-02-05

The World Health Organization (WHO) recommends flexible solid oral dosage forms such as dispersible tablet as the preferred formulation for (young) children, especially in developing/low- and middle-income countries, LMIC. The aim of this study was to assess experience, perceptions of acceptability, and formulation preferences, among 10 oral dosage forms for young children in a sample of end-users in Nigeria as an exemplar LMIC. Using a semi-structured and validated questionnaire, 148 caregivers were surveyed. Acceptability was assessed by level of liking using a 3-point Likert scale and ease of administration. Preference was assessed from participants' dosage form of choice. Oral dosage forms assessed were those mentioned in the British National Formulary for children, 2013. The formulation perceived as the most acceptable was the chewable/suckable tablet. However, preference was for liquids. Specifically with the dispersible tablet, whilst 89% (n=111) of caregivers of young children found it easy-to-administer, only 50% of children liked it. There is a gap between the proposal of dispersible tablet as the preferred dosage form for young children and caregivers' perceptions of acceptability and preference. Educational strategies to increase acceptability of dispersible tablets as the preferred formulation for young children would be required. Copyright © 2017 Elsevier B.V. All rights reserved.

An introduction to fast dissolving oral thin film drug delivery systems: a review.

PubMed

Kathpalia, Harsha; Gupte, Aasavari

2013-12-01

Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

Biorelevant in-vitro performance testing of orally administered dosage forms.

PubMed

Reppas, Christos; Vertzoni, Maria

2012-07-01

This review focuses on the evolution and current status of biorelevant media and hydrodynamics, and discusses the usefulness of biorelevant performance testing in the evaluation of specific dosage form related lumenal processes. During the last 15 years our knowledge of the gastrointestinal environment (including the lower gut) has improved dramatically and biorelevant media composition and, to a lesser extent, biorelevant hydrodynamics, have been refined. Biorelevant dissolution/release testing is useful for the evaluation of formulation and food effects on plasma levels after administration of immediate release dosage forms containing low solubility compounds and after administration of extended release products. Lumenal disintegration times of immediate release dosage forms and the bile acid sequestering activity of resins in the lumen can also be successfully forecasted with biorelevant in vitro testing. Biorelevant in-vitro performance testing is an important tool for evaluating intralumenal dosage form performance. Since the formulation of new active pharmaceutical ingredients for oral delivery is more challenging than ever before, efforts to improve the predictability of biorelevant tests are expected to continue. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Nasal Drug Delivery in Traditional Persian Medicine

PubMed Central

Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

2013-01-01

Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

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

PubMed

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.

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

PubMed Central

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

Dry elixir formulations of dexibuprofen for controlled release and enhanced oral bioavailability.

PubMed

Kim, Seo-Ryung; Kim, Jin-Ki; Park, Jeong-Sook; Kim, Chong-Kook

2011-02-14

The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit(®) RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19 μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit(®) RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen. Copyright © 2010 Elsevier B.V. All rights reserved.

Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion.

PubMed

Vynckier, A-K; De Beer, M; Monteyne, T; Voorspoels, J; De Beer, T; Remon, J P; Vervaet, C

2015-08-01

In this study hot-melt co-extrusion is used as processing technique to manufacture a fixed-dose combination product providing enteric protection to naproxen incorporated in the core and immediate release to esomeprazole magnesium embedded in the coat. The plasticizing effect of naproxen and triethyl citrate (TEC) was tested on the enteric polymers investigated (Eudragit(®) L100-55, HPMC-AS-LF and HPMCP-HP-50). Core matrix formulations containing HPMC-AS-LF, TEC and a naproxen load of 15, 30 and 50% were processed and characterized. The in vitro naproxen release in 0.1N HCl was prevented for 2h for all formulations. The physicochemical state of the drug in the extrudates was determined and a stability study was performed. Intermolecular interactions between naproxen and polymer were identified using attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. When esomeprazole magnesium was formulated in a polyethylene oxide 100K:polyethylene glycol 4K (1:1) matrix, separated from the naproxen-containing layer, the formulation could be easily processed and complete in vitro drug release was observed after 45 min. When co-extruding the core/coat dosage form it was observed that a third layer of polymer, separating the naproxen loaded enteric formulation in the core from the coat, is required to prevent degradation of the acid-labile esomeprazole magnesium at the core/coat interface. Copyright © 2015 Elsevier B.V. All rights reserved.

Prescribing Errors Involving Medication Dosage Forms

PubMed Central

Lesar, Timothy S

2002-01-01

CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138

Ease of opening of blistered solid dosage forms in a senior citizens target group.

PubMed

Braun-Münker, Myriam; Ecker, Felix

2016-10-30

Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics.

PubMed

Chen, Mei-Ling

2006-01-01

Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been attributed to the distinctions in the genetic, physiological and pathological factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic differences are also known to be influenced by several extrinsic factors such as socioeconomic background, culture, diet and environment. However, it is noted that other factors related to dosage regimen and dosage form have largely been ignored or overlooked when conducting or analysing pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential interactions can arise between the characteristics of ethnicity/race and a unique feature of dosage regimen or dosage form used in the study, which may partly account for the observed pharmacokinetic/pharmacodynamic differences between ethnic/racial groups. Ethnic/racial differences in pharmacokinetics/pharmacodynamics can occur from drug administration through a specific route that imparts distinct pattern of absorption, distribution, transport, metabolism or excretion. For example, racial differences in the first-pass metabolism of a drug following oral administration may not be relevant when the drug is applied to the skin. On the other hand, ethnic/racial difference in pharmacokinetics/pharmacodynamics can also happen via two different routes of drug delivery, with varying levels of dissimilarity between routes. For example, greater ethnic/racial differences were observed in oral clearance than in systemic clearance of some drugs, which might be explained by the pre-systemic factors involved in the oral administration as opposed to the intravenous administration. Similarly, changes in the dose frequency and/or duration may have profound impact on the ethnic/racial differences in pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or receptors at high drug concentrations is a possible reason for many observed ethnic/racial discrepancies between single- and multiple-dose regimens, or between low- and high-dose administrations. The presence of genetic polymorphism of enzymes and/or transporters can further complicate the analysis of pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within the same dosage regimen, the use of different dosage forms may trigger significantly different pharmacokinetic/pharmacodynamic responses in various ethnic/racial groups, given that different dosage forms may exhibit different rates of drug release, may release the drug at different sites, and/or have different retention times at specific sites of the body. It is thus cautioned that the pharmacokinetic/pharmacodynamic data obtained from different ethnic/racial groups cannot be indiscriminately compared or combined for analysis if there is a lack of homogeneity in the apparent 'extrinsic' factors, including dosage regimen and dosage form.

Evaluation of the efficacy of insecticidal coatings based on teflutrin and chlorpyrifos against Rhynchophorus ferrugineus.

PubMed

Pugliese, Massimo; Rettori, Andrea Alberto; Martinis, Roberto; Al-Rohily, Khalid; Velate, Suresh; Moideen, Mohamed Ashraf; Al-Maashi, Ali

2017-08-01

The date palm (Phoenix dactylifera L.), an important economic resource for many nations worldwide, has recently been threatened by the presence of different insect pests, like the red palm weevil (RPW) Rhynchophorus ferrugineus. Two products, a glue (polyvinyl acetate) and an oil (raw linseed oil) were used as coatings and applied together with a repellent and two insecticides (teflutrin and chlorpyrifos) at different dosages on two species of palm (P. dactylifera and P. canariensis). Phytotoxic effects of the treatments were evaluated in a greenhouse on 260 potted palms (130 P. dactylifera and 130 P. canariensis) and no negative effects were observed. Afterwards, a trial lasting 400 days was carried out in a nursery located in Sicily (south Italy), treating 572 potted palm trees (286 P. dactylifera and 286 P. canariensis) with an average diameter at the base of 18-20 cm. After 400 days, 48% of the untreated palms were infested, while only 3% of date palms and 7% of Canary palms treated with insecticide at lower dosages were infested. The application of an insecticide-based coating is a good strategy to control and prevent the red palm weevil infestation, in particular on date palms. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Anodizing of High Electrically Stressed Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flores, P.; Henderson, D. J.; Good, D. E.

2013-06-01

Anodizing creates an aluminum oxide coating that penetrates into the surface as well as builds above the surface of aluminum creating a very hard ceramic-type coating with good dielectric properties. Over time and use, the electrical carrying components (or spools in this case) experience electrical breakdown, yielding undesirable x-ray dosages or failure. The spool is located in the high vacuum region of a rod pinch diode section of an x-ray producing machine. Machine operators have recorded decreases in x-ray dosages over numerous shots using the reusable spool component, and re-anodizing the interior surface of the spool does not provide themore » expected improvement. A machine operation subject matter expert coated the anodized surface with diffusion pump oil to eliminate electrical breakdown as a temporary fix. It is known that an anodized surface is very porous, and it is because of this porosity that the surface may trap air that becomes a catalyst for electrical breakdown. In this paper we present a solution of mitigating electrical breakdown by oiling. We will also present results of surface anodizing improvements achieved by surface finish preparation and surface sealing. We conclude that oiling the anodized surface and using anodized hot dip sealing processes will have similar results.« less

Synthesis and properties of hydroxy acrylic resin with high solid content

NASA Astrophysics Data System (ADS)

Yu, Zhen; Hu, Mingguang; Cui, Han; Xiao, Jijun

2017-10-01

Manufacturers of automotive repair finishes are tending to reduce more and more the level of volatile organic compounds in their paints in order to comply with increasingly strict environmental legislation. A high solid hydroxy acrylic resin was synthesised using CARDURA E10 and a type of hydroxyacrylic acid resin, its' acid value, hydroxylvalue, viscosity, structure, morphology was measured and film-forming properties after curing were characterised. The results show that the addition of CARDURA E10 in the copolymer composition significantly reduced the viscosity of the polymer system, improved the solid content of the resin and the physical properties of the coating. The hydroxyl acrylate resin with solid content of 90% and excellent comprehensive performance were successfully prepared by controlling the initiator dosage, polymerization temperature and monomer ratio.

An empirical model for dissolution profile and its application to floating dosage forms.

PubMed

Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul

2014-06-02

A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

PubMed Central

Sun, Jin; Shi, Jie-Ming; Zhang, Tian-Hong; Gao, Kun; Mao, Jing-Jing; Li, Bing; Sun, Ying-Hua; He, Zhong-Gui

2005-01-01

AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves. PMID:16052686

The influence of Surelease and sodium alginate on the in-vitro release of tamsulosin hydrochloride in pellet dosage form.

PubMed

Kim, Min-Soo; Jun, Seoung Wook; Lee, Sibeum; Lee, Tae Wan; Park, Jeong-Sook; Hwang, Sung-Joo

2005-06-01

The objective of this study was to prepare controlled-release pellets containing 0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers with Surelease and sodium alginate. The release of tamsulosin HCl from pellets coated with the commercial aqueous ethylcellulose dispersion (Surelease) was investigated at different coating loads. In addition, the effect of sodium alginate on drug release was investigated by varying the ratio of sodium alginate to microcrystalline cellulose (MCC). Dissolution studies were first performed in 500 mL simulated gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross sections were examined by scanning electron microscopy (SEM). Apparently, the spherical pellets were prepared using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from Surelease-coated pellets were significantly affected by changing the content of Surelease, the pH of the dissolution medium and the ratio of sodium alginate to MCC. The drug release rates not only decreased with increase in the coating load, but also increased when the pH of the dissolution medium was increased from 1.2 to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results suggest that Surelease and sodium alginate would be useful excipients in the preparation of controlled-release pellets with the desired release profiles.

Formulation and characterization of sustained release dosage form of moisture sensitive drug

PubMed Central

Patel, Priya; Dave, Abhishek; Vasava, Amit; Patel, Paresh

2015-01-01

Objective: The purpose of this study was to prepare sustained release tablet of moisture sensitive drug like Ranitidine Hydrochloride for treatment of gastroesophageal reflux disease along with the improvement of moisture stability to get better therapeutic efficacy. Materials and Methods: Pan coating technique was used for coating of the tablet. Film coating was done using Eudragit RLPO and Eugragit EPO as coating polymer. 32 full factorial design was applied for optimization purpose, and 9 runs were conducted. In that Eudragit RLPO and Eudragit EPO taken as an independent variables and moisture gain and Cummulative Drug Release (CDR) were taken as dependent variables. Drug and excipient compatibility was done using differential scanning calorimetry and Fourier transform infrared spectroscopy study. The tablet was evaluated for precompression parameter and all postcompression parameter. Stability study was carried out at room temperature (30°C ± 2°C/65% ± 5% relative humidity). Final formulation was compared with marketed formulation RANTEC 300. Result: Tablets were passing out all precompression parameter along with postcompression parameter. Stability study shows that the parameter such as hardness, friability, and dissolution are in the range. Hence, there is no significant change shown after stability study. Our final formulation was compared with marketed formulation RANTEC 300 and result demonstrates that our final formulation have less moisture gain and give release up to 12 h. Conclusion: The result of present study demonstrates that final formulation has less moisture gain and getting desired CDR for sustained release of drug. On the basis of all study, it was concluded that the tablet was coated by combination of Eudragit RLPO 10% and Eudragit EPO 10% give better result. This formation provided promising approach for the drug release up to 12 h for moisture sensitive drug like ranitidine hydrochloride. PMID:25838994

Determination of azathioprine and its related substances by capillary zone electrophoresis and its application to pharmaceutical dosage forms assay.

PubMed

Shafaati, A; Clark, B J

2000-03-01

The development of a stability-indicating capillary zone electrophoresis (CZE) method for the determination of the drug azathioprine (AZA) and its related substances in bulk and dosage forms is described. Theophylline was used as an internal standard to improve quantitative results. The method was fully validated in terms of repeatability (n = 10, RSD for migration time and peak area ratio were 0.15% and 0.60%, respectively), reproducibility (n = 5, RSD of peak area ratio was 0.84%), linearity at two ranges of the azathioprine concentration, limits of detection (LOD) and quantitation (LOQ), and robustness. The method was applied for determination of the drug in bulk and a commercial tablet dosage form (recovery 98.3-101.3%) and in powder for injection (recovery 98.7-100.6%). The method was fast and reliable for the analysis of AZA and its related substances in bulk and dosage forms.

Development and validation of multivariate calibration methods for simultaneous estimation of Paracetamol, Enalapril maleate and hydrochlorothiazide in pharmaceutical dosage form

NASA Astrophysics Data System (ADS)

Singh, Veena D.; Daharwal, Sanjay J.

2017-01-01

Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5-35 μg mL- 1, 5-40 μg mL- 1 and 5-40 μg mL- 1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

PubMed

Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

2018-02-01

The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

Influence of limonene on the bioavailability of nicardipine hydrochloride from membrane-moderated transdermal therapeutic systems in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2002-10-24

The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form. Copyright 2002 Elsevier Science B.V.

Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydrochloride in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-05-01

A membrane-moderated transdermal therapeutic system of nicardipine hydrochloride was developed using 2% w/w hydroxypropylcellulose (HPC) gel as a reservoir system containing 5% w/w of menthol as a penetration enhancer. The permeability flux of nicardipine hydrochloride through the ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28% w/w vinyl acetate) or EVA 2825 membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new transdermal therapeutic system for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED, and 2% w/w HPC gel as reservoir containing 5% w/w of menthol as a penetration enhancer. In vivo studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 26h with improved bioavailability in comparison with the immediate release capsule dosage form.

Formulation and in vivo evaluation of membrane-moderated transdermal therapeutic systems of nicardipine hydrochloride using carvone as a penetration enhancer.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-01-01

A membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride was developed using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 8%w/w of carvone as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38, or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28%w/w vinyl acetate) or EVA 2825 membrane/skin composite also was studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED and 2%w/w HPC gel as reservoir containing 8%w/w of carvone as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 23 hr with improved bioavailability in comparison with the immediate-release capsule dosage form.

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

PubMed

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

2015-07-05

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

A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

PubMed

Jiang, Bowen; Yu, Hua; Zhang, Yongrong; Feng, Hanping; Hoag, Stephen W

2017-12-01

There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads. In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1. No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer. We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry.

PubMed

Corá, Luciana A; Romeiro, Fernando G; Américo, Madileine F; Oliveira, Ricardo Brandt; Baffa, Oswaldo; Stelzer, Murilo; Miranda, José Ricardo de Arruda

2006-01-01

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations.

Nano/micro/meso scale interactions in mechanics of pharmaceutical solid dosage forms

NASA Astrophysics Data System (ADS)

Akseli, Ilgaz

Oral administration in form tablets has been the most common method for delivering drug to the human systemic blood circulation accurately and reproducibly due to its established manufacturing methods and reliability as well as cost. The mechanical criteria for a successful powder-to-tablet processing are good flowability, compressibility and compactibility that are closely related to the mechanical and adhesion properties of the particles and particle strength. In this thesis, air-coupled acoustic and ultrasonic techniques are presented and demonstrated as noncontact and nondestructive methods for physical (mechanical) integrity monitoring and mechanical characterization of tablets. A testing and characterization experimental platform for defect detection, coating thickness and mechanical property determination of tablets was also developed. The presented air-coupled technique was based on the analysis of the transient vibrational responses of a tablet in both temporal and spectral domains. The contact ultrasonic technique was based on the analysis of the propagation speed of an acoustic pulse launched into a tablet and its reflection from the coat-core interface of the tablet. In defect monitoring, the ultimate objective is to separate defective tablets from nominal ones. In the case of characterization, to extract the coating layer thicknesses and mechanical properties of the tablets from a subset of the measured resonance frequencies, an iterative computational procedure was demonstrated. In the compaction monitoring experiments, an instrumented punch and a cylindrical die were employed to extract the elasticity properties of tablets during compaction. To study the effect of compaction kinetics on tablet properties and defect, finite element analyses of single layer and bilayer tablets were performed. A noncontact work-of-adhesion technique was also demonstrated to determine the work-of-adhesion of pharmaceutical powder particles.

Specific aspects of gastro-intestinal transit in children for drug delivery design.

PubMed

Bowles, Alexandra; Keane, Joanne; Ernest, Terry; Clapham, David; Tuleu, Catherine

2010-08-16

This mini-review discusses relevant aspects of gastro-intestinal transit in different ages of paediatric patients with an attempt to highlight factors which should be considered in oral dosage form design, in particular multi-particulate dosage forms. This emphasis is due to multi-particulates possessing many of the benefits of liquid oral formulations (such as ease of swallowing and dose adaptability) without many of their drawbacks (such as stability issues and lack of enteric or modified release functionalities). It is commonly stated that children are not merely small adults with regards to medicines. However, there has been very little research regarding how different dosage forms transit through the gastro-intestinal tract in children compared to adults, due to both ethical and practical hurdles. Due to this lack of studies on dosage form transit in children, information which was available on the transit of food, milk and liquids (often dependent upon the age of the patient) has been used to look at how various aspects of transit vary with age and, where possible, when they reach adult values and how these may affect the fate of dosage forms in vivo: swallowability, oesophageal transit, gastric emptying and pH, intestinal and colonic transit are discussed. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

PubMed

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.

Integrating tristimulus colorimetry into pharmaceutical development for color selection and physical appearance control: a quality-by-design approach.

PubMed

Hetrick, Evan M; Vannoy, Jeffrey; Montgomery, Laura L; Pack, Brian W

2013-08-01

The color of pharmaceutical dosage forms can be an important aspect of product branding and patient compliance with a dosing regimen. During the development of drug products, it is important to understand the stability of not only the active pharmaceutical ingredient but also the color and appearance of the tablet or capsule. Currently, the most common method to ensure color stability is to conduct a visual test throughout a stability study. This visual test is subjective and can be expensive, especially if there is a failure late in development or after marketing approval. This work describes a series of studies using accelerated conditions (i.e., heat, humidity, and light) and logistic regression analyses that have been developed to determine the relative stability ranking of multiple color coatings early in development to provide an increased probability of technical success on long-term stability studies and to avoid coatings whose visual appearance may change over time. Once this relative stability ranking has been established, the stability advantages can be assessed versus any manufacturing/processing liabilities of the selected coating in order to make a data-driven decision around coating selection. This work reviews the basic fundamentals of colorimetry, followed by the description of a consistent experimental approach to correlate a visual rating with an instrumental measurement (e.g., dE(*) from a colorimeter) to remove the subjectivity from the assessment. This approach represents a novel strategy for establishing a probabilized correlation between the quantitative instrumental color measurement and the visual rating of the same color change. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed

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.

DIFFERENTIAL KILLING EFFECT IN JUTE BY X-RAYS AND RADIOISOTOPES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, R.K.

1962-01-01

Treatments with x rays and BETA rays from P/sup 32/ and S/sup 35/ on dry and pure line seeds of three varieties of Corchorus olitorius L. and two varieties of C. capsularis L. produced differential killing effect. 0ver the range of dosages applied treatments with P/sup 32/ and S/sup 35/ showed lesser killing effect than treatments with x rays. From the counts of survivals at maturity, the LD/sub 50/with x rays was found to lie between 64000 and r0000 r for the varieties of C. olitorius and between 80000 and 90000 r for the varieties of C. capsularis. While themore » usual relationship of decrease in survival with increase in dosage was established with x rays, treatments with P/sup 32/ and S/ sup 35/ often showed increased survival compared to the control. The differential killing effect of the three mutagens is discussed as a consequence of difference in ion density. The obscure effects of radioisotopes may be due to production of substances reacting in the form of stimulation or protective agents. The differential radiosensitivity of the two species may be due to difference in factors like seed size and thickness of seed coat, which influence the non- genetical effects of irradiation. (auth)« less

Current opinions and recommendations of paediatric healthcare professionals – The importance of tablets: Emerging orally disintegrating versus traditional tablets

PubMed Central

Alyami, Hamad; Koner, Jasdip; Terry, David; Mohammed, Afzal R.

2018-01-01

The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT’s is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional’s opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties. PMID:29489871

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

PubMed

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.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

PubMed

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of spherical silicate to prepare solid dispersion dosage forms with aqueous polymers.

PubMed

Nagane, Kentaro; Kimura, Susumu; Ukai, Koji; Takahashi, Chisato; Ogawa, Noriko; Yamamoto, Hiromitsu

2015-09-30

The objective of this study is to prepare and characterize solid dispersions of nifedipine (NP) using porous spherical silicate micro beads (MB) that were approximately 100 μm in diameter with vinylpyrrolidone/vinyl acetate copolymer (PVP/VA) and a Wurster-type fluidized bed granulator. Compared with previously reported solid dispersion using only MB, the supersaturation of NP dissolved from the proposed system of MB and PVP/VA was maintained during dissolution tests. The proposed system produced a solid dispersion product coated on MB, and morphology was maintained after the coating process to prepare solid dispersion; therefore, the powder characteristics, such as flowability of the proposed solid dispersion product, was tremendously preferable to that of the conventional spray-dried solid dispersions of NP with PVP/VA, expecting to make the consequent manufacturing processes easy for development. Another advantage in the terms of manufacturing is its simple process to prepare solid dispersion by spraying the drug and polymer that were dissolved in an organic solvent onto a MB in a Wurster-type fluidized bed granulator, thus, simplifying the optimization and scale-up with ease. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate.

PubMed

Amrutkar, P P; Chaudhari, P D; Patil, S B

2012-01-01

Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

21 CFR 206.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

21 CFR 206.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

21 CFR 206.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms.

PubMed

Zajicek, Anne; Fossler, Michael J; Barrett, Jeffrey S; Worthington, Jeffrey H; Ternik, Robert; Charkoftaki, Georgia; Lum, Susan; Breitkreutz, Jörg; Baltezor, Mike; Macheras, Panos; Khan, Mansoor; Agharkar, Shreeram; MacLaren, David Douglas

2013-10-01

Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

The influence of averaging procedure on the accuracy of IVIVC predictions: immediate release dosage form case study.

PubMed

Ostrowski, Michalł; Wilkowska, Ewa; Baczek, Tomasz

2010-12-01

In vivo-in vitro correlation (IVIVC) is an effective tool to predict absorption behavior of active substances from pharmaceutical dosage forms. The model for immediate release dosage form containing amoxicillin was used in the presented study to check if the calculation method of absorption profiles can influence final results achieved. The comparison showed that an averaging of individual absorption profiles performed by Wagner-Nelson (WN) conversion method can lead to lose the discrimination properties of the model. The approach considering individual plasma concentration versus time profiles enabled to average absorption profiles prior WN conversion. In turn, that enabled to find differences between dispersible tablets and capsules. It was concluded that in the case of immediate release dosage form, the decision to use averaging method should be based on an individual situation; however, it seems that the influence of such a procedure on the discrimination properties of the model is then more significant. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Topical cream-based dosage forms of the macrocyclic drug delivery vehicle cucurbit[6]uril.

PubMed

Seif, Marian; Impelido, Michael L; Apps, Michael G; Wheate, Nial J

2014-01-01

The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery.

Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

PubMed

Gröning, R; Cloer, C; Müller, R S

2006-07-01

The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

Topical Cream-Based Dosage Forms of the Macrocyclic Drug Delivery Vehicle Cucurbit[6]uril

PubMed Central

Seif, Marian; Impelido, Michael L.; Apps, Michael G.; Wheate, Nial J.

2014-01-01

The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery. PMID:24454850

Cadmium Removal from Contaminated Water Using Polyelectrolyte-Coated Industrial Waste Fly Ash

PubMed Central

Olabemiwo, Fatai A.; Oyehan, Tajudeen A.; Khaled, Mazen

2017-01-01

Fly ash (FA) is a major industrial waste generated from power stations that add extra cost for proper disposal. Recent research efforts have consequently focused on developing ways to make use of FA in environmentally sound applications. This study, therefore, investigates the potential ability of raw fly ash (RFA) and polyelectrolyte-coated fly ash (PEFA) to remove cadmium (Cd) from polluted water. Using layer-by-layer approach, functionalized fly ash was coated with 20 layers from 0.03% (v/v) of cationic poly(diallyldimethylammonium chloride) (PDADMAC) and anionic polystyrene sulfonate (PSS) solutions. Both surface morphology and chemical composition of the adsorbent (PEFA) were characterized using Field-Emission Scanning Electron Microscope (FE-SEM), X-Ray Diffraction (XRD), Fourier-Transform Infrared (FTIR), and X-Ray Fluorescence (XRF) techniques. The effects of pH, adsorbent dosage, contact time, initial contaminant concentration, and mixing rate of the adsorption of Cd were also studied in batch mode experiments. Results of the study revealed that a 4.0 g/L dosage of PEFA removed around 99% of 2.0 mg/L of Cd in 15 min at 150 rpm compared to only 27% Cd removal achieved by RFA under the same conditions. Results also showed that adsorption by PEFA followed both Langmuir and Freundlich models with correlation coefficients of 98% and 99%, respectively. PMID:28680373

Toxicological assessment of Anionic Methacrylate Copolymer: I. Characterization, bioavailability and genotoxicity.

PubMed

Eisele, Johanna; Haynes, Geoff; Kreuzer, Knut; Hall, Caroline

2016-12-01

Anionic Methacrylate Copolymer (AMC) is a fully polymerized copolymer used in the pharmaceutical industry as an enteric/delayed-release coating to permit the pH-dependent release of active ingredients in the gastrointestinal tract from oral dosage forms. This function is of potential use for food supplements. Oral administration of radiolabeled copolymer to rats resulted in the detection of chemically unchanged copolymer in the feces, with negligible absorption (<0.1%). AMC is therefore determined not to be bioavailable. Within a genotoxicity test battery AMC did not show any evidence of genotoxicity in bacteria and mammalian cells. Furthermore, no genotoxic effects occurred in vivo within a micronucleus test. There would therefore appear to be no safety concerns under intended conditions of oral use for the discussed toxicological endpoints. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.

PubMed

Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

2011-01-01

The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR. © 2011 Pharmaceutical Society of Japan

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

PubMed

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-faceted healthcare environment complicate decision making regarding oral dosage form modification and administration. This systematic review has highlighted the key factors influencing the knowledge, attitudes and beliefs of patients and healthcare professionals about oral dosage form modifications. The findings suggest that in order to optimise oral medicine modification practices the needs of individual patients should be routinely and systematically assessed and decision-making should be supported by evidence based recommendations with multidisciplinary input. Further research is needed to optimise oral dosage form modification practices and the factors identified in this review should be considered in the development of future interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parr, A.F.; Beihn, R.M.; Franz, R.M.

1987-12-01

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

[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.

PubMed

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.

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children's Acceptability of Oral Formulations (CALF) Study.

PubMed

Ranmal, Sejal R; Cram, Anne; Tuleu, Catherine

2016-11-30

A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

Issues impacting therapeutic outcomes in pediatric patients: an overview.

PubMed

Kalra, Atin; Goindi, Shishu

2014-01-01

The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

Federal Register 2010, 2011, 2012, 2013, 2014

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; Phenylpropanolamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

21 CFR 206.10 - Code imprint required.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

21 CFR 206.10 - Code imprint required.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

21 CFR 206.10 - Code imprint required.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

75 FR 9333 - Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin AGENCY: Food and... dose range for use of an injectable solution of tilmicosin phosphate for treatment of respiratory... 300 (tilmicosin injection, USP) Injection, available by veterinary prescription for use in the...

76 FR 38554 - Oral Dosage Form New Animal Drugs; Amprolium

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

.... 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 regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by Cross...

77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Gentamicin Sulfate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA...

75 FR 76259 - Oral Dosage Form New Animal Drugs; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

.... FDA-2010-N-0002] 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 regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by...

75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Novartis Animal...

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

Federal Register 2010, 2011, 2012, 2013, 2014

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...

76 FR 72619 - Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 [Docket No. FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule; technical amendment. SUMMARY: The Food and Drug...

Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers.

PubMed

Ishihara, Tsutomu; Maeda, Taishi; Sakamoto, Haruka; Takasaki, Naoko; Shigyo, Masao; Ishida, Tatsuhiro; Kiwada, Hiroshi; Mizushima, Yutaka; Mizushima, Tohru

2010-10-11

The accelerated blood clearance (ABC) phenomenon is induced upon repeated injections of poly(ethylene glycol) (PEG)-coated colloidal carriers. It is essential to suppress this phenomenon in a clinical setting because the pharmacokinetics must be reproducible. In this study, we evaluated the induction of the ABC phenomenon using nanoparticles coated with various hydrophilic polymers instead of PEG. Nanoparticles encapsulating prostaglandin E1 were prepared by the solvent diffusion method from a blend of poly(lactic acid) (PLA) and block copolymers consisting of various hydrophilic polymers and PLA. Coating of nanoparticles with poly(N-vinyl-2-pyrrolidone) (PVP), poly(4-acryloylmorpholine), or poly(N,N-dimethylacrylamide) led to extended residence of the nanoparticles in blood circulation in rats, although they had a shorter half-life than the PEG-coated nanoparticles. The ABC phenomenon was not induced upon repeated injection of PVP-coated nanoparticles at various time intervals, dosages, or frequencies, whereas it was elicited by PEG-coated nanoparticles. In addition, anti-PVP IgM antibody, which is estimated to be one of the crucial factors for induction of the ABC phenomenon, was not produced after injection of PVP-coated nanoparticles. These results suggest that the use of PVP, instead of PEG, as a coating material for colloidal carriers can evade the ABC phenomenon.

Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

PubMed

Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

2015-01-01

Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

21 CFR 520.1448 - Monensin oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... layer chromatography, the R f value must be comparable to a reference standard (the R f value is the...

21 CFR 520.1448 - Monensin oral dosage forms.

Code of Federal Regulations, 2010 CFR

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... layer chromatography, the R f value must be comparable to a reference standard (the R f value is the...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... INFORMATION: Bayer HealthCare LLC, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201, filed a...

75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Flunixin AGENCY: Food and... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... copy of BANAMINE-S, sponsored by Schering-Plough Animal Health Corp. under NADA 101-479. The ANADA is...

75 FR 12981 - Oral Dosage Form New Animal Drugs; Tetracycline Powder

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tetracycline Powder AGENCY: Food and Drug... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... approval of this product. This change is being made to improve the accuracy of the animal drug regulations...

76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug application (NADA) from Virbac AH...

77 FR 4226 - Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application.... 801-808. List of Subjects in 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug...

75 FR 54018 - Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

Phase 2 study of sodium phenylbutyrate in ALS.

PubMed

Cudkowicz, Merit E; Andres, Patricia L; Macdonald, Sally A; Bedlack, Richard S; Choudry, Rabia; Brown, Robert H; Zhang, Hui; Schoenfeld, David A; Shefner, Jeremy; Matson, Samantha; Matson, Wayne R; Ferrante, Robert J

2009-04-01

The objective of the study was to establish the safety and pharmacodynamics of escalating dosages of sodium phenylbutyrate (NaPB) in participants with ALS. Transcription dysregulation may play a role in the pathogenesis of ALS. Sodium phenylbutyrate, a histone deacetylase inhibitor, improves transcription and post-transcriptional pathways, promoting cell survival in a mouse model of motor neuron disease. Forty research participants at eight sites enrolled in an open-label study. Study medication was increased from 9 to 21 g/day. The primary outcome measure was tolerability. Secondary outcome measures included adverse events, blood histone acetylation levels, and NaPB blood levels at each dosage. Twenty-six participants completed the 20-week treatment phase. NaPB was safe and tolerable. No study deaths or clinically relevant laboratory changes occurred with NaPB treatment. Histone acetylation was decreased by approximately 50% in blood buffy-coat specimens at screening and was significantly increased after NaPB administration. Blood levels of NaPB and the primary metabolite, phenylacetate, increased with dosage. While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels.

Formulation development and in-vitro/in-vivo correlation for a novel Sterculia gum-based oral colon-targeted drug delivery system of azathioprine.

PubMed

Nath, Bipul; Nath, Lila Kanta

2013-11-01

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.

Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.

PubMed

Andreas, Cord J; Tomaszewska, Irena; Muenster, Uwe; van der Mey, Dorina; Mueck, Wolfgang; Dressman, Jennifer B

2016-08-01

Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests. Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches. Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form. It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

PubMed Central

Bellinger, Andrew M.; Jafari, Mousa; Grant, Tyler M.; Zhang, Shiyi; Slater, Hannah C.; Wenger, Edward A.; Mo, Stacy; Lee, Young-Ah Lucy; Mazdiyasni, Hormoz; Kogan, Lawrence; Barman, Ross; Cleveland, Cody; Booth, Lucas; Bensel, Taylor; Minahan, Daniel; Hurowitz, Haley M.; Tai, Tammy; Daily, Johanna; Nikolic, Boris; Wood, Lowell; Eckhoff, Philip A.; Langer, Robert; Traverso, Giovanni

2017-01-01

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. PMID:27856796

Development and evaluation of a monolithic floating dosage form for furosemide.

PubMed

Menon, A; Ritschel, W A; Sakr, A

1994-02-01

The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

Bioavailability of AREDS1 micronutrients from softgel capsules and tablets: a pilot study

PubMed Central

Johnson, Elizabeth J.; Vishwanathan, Rohini; Rasmussen, Helen M.

2014-01-01

Purpose The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, β-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. Methods A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. Results Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for β-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus two), but it was not sufficient to reach the level achieved by the full dose of either four tablets or two softgels. A model-dependent analysis permitted an estimation of the percentage of micronutrients absorbed, with zinc, the single most important ingredient, absorbed at about a 10% level. Conclusions The results suggest modestly contradictory requirements in the dosage form for water-soluble and lipid-soluble ingredients, as based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms, and most nutrients between AREDS1 and AREDS2 (full dose) formulations relative to the significant variations observed within this controlled population. The results emphasize the importance of defining the requisite bioavailability of each micronutrient and the influence of the dosage form that provides it. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with AMD and their significant metabolic and health consequences, establishing efficient means of supplementation are of continuing epidemiologic interest. PMID:25352732

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

PubMed Central

Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

2013-01-01

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

Preformulation considerations for controlled release dosage forms. Part I. Selecting candidates.

PubMed

Chrzanowski, Frank

2008-01-01

The physical-chemical properties of interest for controlled release (CR) dosage form development presented are based on the author's experience. Part I addresses selection of the final form based on a logical progression of physical-chemical properties evaluation of candidate forms and elimination of forms with undesirable properties from further evaluation in order to simplify final form selection. Several candidate forms which could include salt, free base or acid, polymorphic and amorphic forms of a new chemical entity (NCE) or existing drug substance (DS) are prepared and evaluated for critical properties in a scheme relevant to manufacturing processes, predictive of problems, requiring small amounts of test materials and simple analytical tools. A stability indicating assay is not needed to initiate the evaluation. This process is applicable to CR and immediate release (IR) dosage form development. The critical properties evaluated are melting, crystallinity, solubilities in water, 0.1 N HCl, and SIF, hygrodymamics, i.e., moisture sorption and loss at extremes of RH, and LOD at typical wet granulation drying conditions, and processability, i.e., corrosivity, and filming and/or sticking upon compression.

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core.

PubMed

Homar, Miha; Dreu, Rok; Kerc, Janez; Gasperlin, Mirjana

2009-09-01

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12-40% could be achieved with the degree of encapsulation ranging from 60-82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.

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

PubMed

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.

Regulatory perspectives on acceptability testing of dosage forms in children.

PubMed

Kozarewicz, Piotr

2014-08-05

Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Fourth-order derivative spectrophotometric method for simultaneous determination of pseudoephedrine and naproxen in pharmaceutical dosage forms

PubMed Central

Souri, Effat; Mosafer, Amir; Tehrani, Maliheh Barazandeh

2016-01-01

Combination dosage forms of naproxen sodium and pseudoephedrine hydrochloride are used for symptomatic treatment of cold and sinus disorders. In this study, fourth-order derivative spectrophotometric method was used for simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride. The method was linear over the range of 2-28 μg/ml for pseudoephedrine hydrochloride and 4-200 μg/ml for naproxen sodium. The within-day and between-day coefficient of variation values were less than 5.8% and 2.5% for pseudoephedrine hydrochloride and naproxen sodium, respectively. The application of the proposed method for simultaneous determination of naproxen and pseudoephedrine in dosage forms was demonstrated without any special pretreatment. PMID:27168748

Using the technique of computed tomography for nondestructive analysis of pharmaceutical dosage forms

NASA Astrophysics Data System (ADS)

de Oliveira, José Martins, Jr.; Mangini, F. Salvador; Carvalho Vila, Marta Maria Duarte; ViníciusChaud, Marco

2013-05-01

This work presents an alternative and non-conventional technique for evaluatingof physic-chemical properties of pharmaceutical dosage forms, i.e. we used computed tomography (CT) technique as a nondestructive technique to visualize internal structures of pharmaceuticals dosage forms and to conduct static and dynamical studies. The studies were conducted involving static and dynamic situations through the use of tomographic images, generated by the scanner at University of Sorocaba - Uniso. We have shown that through the use of tomographic images it is possible to conduct studies of porosity, densities, analysis of morphological parameters and performing studies of dissolution. Our results are in agreement with the literature, showing that CT is a powerful tool for use in the pharmaceutical sciences.

In-vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms.

PubMed

Zeitler, J Axel; Gladden, Lynn F

2009-01-01

Tomographic imaging techniques offer new prospects for a better understanding of the quality, performance and release mechanisms of pharmaceutical solid dosage forms. It is only over the last fifteen years that tomography has been applied for the in-vitro characterisation of dosage forms. This review aims to introduce the concept of tomography in a pharmaceutical context, and describes the current state-of-the-art of the four most promising techniques: X-ray computed microtomography, magnetic resonance imaging, terahertz imaging and optical coherence tomography. The basic working principles of the techniques are introduced and the current pharmaceutical applications of the technologies are discussed, together with a comparison of their specific strengths and weaknesses. Possible future developments in these fields are also discussed.

[Oral disintegrating tablets. A new, modern, solid dosage form].

PubMed

Popa, Graţiela; Gafiţanu, Eliza

2003-01-01

The pharmaceutical market shows lately an increasing interest in orally disintegrating tablets, due to their good acceptability among certain age categories (ex. elderly, children), and other patients with difficulties in swallowing classic solid dosage forms. Some of the methods of preparing such tablets have gained industrial applicability: molding, lyophilization, direct compression with highly soluble excipients, super disintegrants and/or effervescent systems. Some of the patients have had a good impact on the pharmaceutical market and more improvements are expected in the next few years, with new drugs to be formulated as fast dissolving dosage formulations.

Preparation of erbium ion-doped TiO2 films and the study of their photocatalytic activity under simulated solar light

NASA Astrophysics Data System (ADS)

Lin, Hongfei; Huang, Yujiao; Li, Shaoni; Luan, Chunhui; Huang, Wei; Wang, Xiaodong; Feng, Xianshe

2017-11-01

A series of erbium ion-doped TiO2 (Er3+-TiO2) films were prepared by a sol-gel dip/spin coating method, and the effect of the dosage of erbium ion (0-2.0 mol%), the films coating layers (1-5 layers), and calcination temperature (400-700 °C) on the film structure and photocatalytic activity were investigated in detail. The films were characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis (TG-DTG) and UV-Vis diffusive reflectance spectra (DRS). The results showed that the films were composed of anatase, and no other TiO2 phases (rutile and brookite). With the increase of the erbium ion dosage, the crystal size decreased. Erbium ion doping could enhance the thermal stability of TiO2 and inhibit the increase of the crystallite size. Meanwhile doping of erbium ions gave rise to three typical absorption peaks within the range of visible light (400-700 nm), locating at 490, 523, and 654 nm, attributed to the transition of 4f electrons. The higher calcination temperature led to higher crystallinity and bigger crystal grains. The photocatalytic performance of the films was evaluated by degradation of methyl orange solution under simulated solar light. The highest quality film we prepared was with 4 layers, 1.0 mol% dosage of erbium ion, and the calcination temperature of 500 °C. With this film, the degradation percentage of 7.8 mg/L methyl orange solution was up to 53.3% under simulated solar light after 6 h photoreaction.

Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized Drug Delivery Systems.

PubMed

Zhang, Jiaxiang; Vo, Anh Q; Feng, Xin; Bandari, Suresh; Repka, Michael A

2018-06-25

Inter-individual variability is always an issue when treating patients of different races, genders, ages, pharmacogenetics, and pharmacokinetic characteristics. However, the development of novel dosage forms is limited by the huge investments required for production line modifications and dosages diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative solution for the development of controlled release dosages because it can produce personalized or unique dosage forms and more complex drug-release profiles. The primary objective of this manuscript is to review the 3D printing processes that have been used in the pharmaceutical area, including their general aspects, materials, and the operation of each AM technique. Advantages and shortcomings of the technologies are discussed with respect to practice and practical applications. Thus, this review will provide an overview and discussion on advanced pharmaceutical AM technologies, which can be used to produce unique controlled drug delivery systems and personalized dosages for the future of personalized medicine.

Surface functionalization of carbon nanotubes by direct encapsulation with varying dosages of amphiphilic block copolymers

NASA Astrophysics Data System (ADS)

Yao, Xueping; Li, Jie; Kong, Liang; Wang, Yong

2015-08-01

Encapsulation of carbon nanotubes (CNTs) by amphiphilic block copolymers is an efficient way to stabilize CNTs in solvents. However, the appropriate dosages of copolymers and the assembled structures are difficult to predict and control because of the insufficient understanding on the encapsulation process. We encapsulate multiwalled CNTs with polystyrene-block-poly (4-vinyl pyridine) (PS-b-P4VP) by directly mixing them in acetic acid under sonication. The copolymer forms a lamellar structure along the surface of CNTs with the PS blocks anchoring on the tube wall and the P4VP blocks exposed to the outside. The encapsulated CNTs achieve good dispersibility in polar solvents over long periods. To increase our understanding of the encapsulation process we investigate the assembled structures and stability of copolymer/CNTs mixtures with changing mass ratios. Stable dispersions are obtained at high mass ratios between the copolymer and CNTs, i.e. 2 or 3, with the presence of free spherical micelles. Transmission electron microscopy and thermal gravimetric analysis determine that the threshold for the complete coverage of CNTs by the copolymer occurs at the mass ratio of 1.5. The coated copolymer layer activates the surface of CNTs, enabling further functionalization of CNTs. For instance, atomic layer deposition of TiO2 produces conformal thin layers on the encapsulated CNTs while isolated TiO2 bumps are produced on the pristine, inert CNTs.

Effect of Cu content on microstructure, mechanical and anti-fouling properties of TiSiN-Cu coating deposited by multi-arc ion plating

NASA Astrophysics Data System (ADS)

Bai, Xuebing; Li, Jinlong; Zhu, Lihui; Wang, Liping

2018-01-01

The copper-doped TiSiN coatings were deposited on 316L stainless steel by reactive co-sputtering in multi-arc ion plating. The surface morphology and structure of the coating were analyzed by scanning electron microcopies, X-ray diffraction and X-ray photoelectron spectroscopy. The hardness was tested using Nano-indentation. The influence of the copper content in the coatings on the structure and mechanical properties of TiSiN-Cu coatings was investigated. Antifouling behaviors of the coatings were evaluated by analyzing adhesion and propagation of P. tricornutum, N. closterium, and Chlorella sp. The TiSiN-Cu coatings had a unique structure of amorphous Si3N4 and nanocrystalline nc-TiN/nc-Cu. The Cu-TiSiN coatings can inhibit effectively attachment and colonization of the algae on the surface. When the copper content increases from 6.75 at.% to 25.15 at.%, the coatings show an obvious decrease in hardness, significantly increase in the surface roughness and greatly weaken in antifouling properties. When the copper content is 6.75 at.%, the coating has the highest hardness with 30 GPa, and the best reduction ratio with 89%, 93% and 57% attachment of P. triceratium, N. closterium and Chlorella sp., respectively. The TiSiN-Cu coating with a copper dosage of 6.75 at.% has the excellent mechanical properties and capability of killing effectively microalgae.

Study of the indoor decontamination using nanocoated woven polyester fabric

NASA Astrophysics Data System (ADS)

Memon, Hafeezullah; Kumari, Naveeta; Jatoi, Abdul Wahab; Khoso, Nazakat Ali

2017-11-01

This research primarily deals with the photocatalytic degradation of methanol in indoor air using nanocoated indoor textiles used for curtains as household textiles. The woven polyester was coated by titanium dioxide by sol gel method, using silicon-based binder. The characterization of the coating has been done using scanning electron microscopy (SEM) image analysis, energy dispersive analysis using X-ray (EDAX) and Fourier transform infrared spectroscopy (FTIR). The DIY instrument providing the similar environment as of indoor was designed to assess the performance of the degradation of formaldehyde under UV light. The photocatalytic degradation rate was measured using the absorption value of the solutions obtained in the result of liquid chromatography of test solution and reagent solution. Different amount of dosages (1-3 %) and different time period of coatings (half hour to 3 h) have been evaluated for optimization.

Extemporaneous compounding in a sample of New Zealand hospitals: a retrospective survey.

PubMed

Kairuz, Therése; Chhim, Srey; Hasan, Fhazeel; Kumar, Karishma; Lal, Aarti; Patel, Roshni; Singh, Ranjani; Dogra, Mridula; Garg, Sanjay

2007-03-23

To determine the extent and nature of extemporaneous compounding of liquid preparations in a sample of New Zealand hospitals. Retrospective data were collected from eight hospitals known to provide compounding services during the period 1 June 2004 to 31 December 2004; including dosage form, volume, and quantity prepared. Data were collected on site from compounding logbooks and batch sheets. Demographic patient data was limited to age and was only collected from pharmacy departments where this information was readily available. Off-label use was analysed where appropriate data were available. 2015 products were compounded over the 7-month period; an average of 251.9 per month. More oral dosage forms were compounded (n=152) compared to topical dosage forms (n=100); 74 drugs required extemporaneous preparation for oral use. There were 16 drugs used in an off-label manner on 144 occasions for paediatric patients. Most off-label drugs were reformulated as suspensions; omeprazole suspension was compounded at all of the hospitals. Off-label use of four drugs (sotalol, labetalol, diazoxide, and clonidine) was analysed for different paediatric age groups. Suspensions are the most frequently compounded dosage form and omeprazole is the drug that is most frequently reformulated. Off-label medicines form a small but integral role in the supply of medicinal products.

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

PubMed

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.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Mucoadhesive films containing chitosan-coated nanoparticles: a new strategy for buccal curcumin release.

PubMed

Mazzarino, Letícia; Borsali, Redouane; Lemos-Senna, Elenara

2014-11-01

Mucoadhesive films containing curcumin-loaded nanoparticles were developed, aiming to prolong the residence time of the dosage form in the oral cavity and to increase drug absorption through the buccal mucosa. Films were prepared by the casting method after incorporation of curcumin-loaded chitosan-coated polycaprolactone nanoparticles into plasticized chitosan solutions. Different molar masses of mucoadhesive polysaccharide chitosan and concentrations of plasticizer glycerol were used to optimize the preparation conditions. Films obtained using medium and high molar mass chitosan were found to be homogeneous and flexible. Curcumin-loaded nanoparticles were uniformly distributed on the film surface, as evidenced by atomic force microscopy and high-resolution field-emission gun scanning electron microscopy (FEG-SEM) images. Analyses of film cross sections using FEG-SEM demonstrate the presence of nanoparticles inside the films. In addition, films proved to have a good rate of hydration in simulated saliva solution, displaying a maximum swelling of around 80% and in vitro prolonged-controlled delivery of curcumin. These results indicate that the mucoadhesive films containing nanoparticles offer a promising approach for buccal delivery of curcumin, which may be particularly useful in the treatment of periodontal diseases that require a sustained drug delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Novel Chromatographic Methods for Simultaneous Quantification of Fish and Wheat Germ Oils Mixture in Pharmaceutical Dosage Forms.

PubMed

El-Yazbi, Amira F; El-Hawiet, Amr

2017-05-01

Two simple, direct and environment-friendly chromatographic methods, high-performance liquid chromatography (HPLC) and high-performance thin layer chromatographic (HPTLC), were developed for the determination of a binary mixture of fish oil (FO) and wheat germ oil (WGO), for the first time, in their pharmaceutical dosage forms with no need for any sample pretreatment. The HPLC separation was carried out using C-18 stationary phase with mobile phase of 15% formic acid (pH 6), methanol and acetonitrile through gradient-elution, 1.5 mL min-1 flow-rate and detection at 215 nm for FO and 280 nm for WGO. HPTLC separation was carried out on silica-coated plates using diethyl ether-petroleum ether (0.5:9.5, v/v) as mobile phase. Detection was at 215 nm for FO and 240 nm for WGO. Regression analysis showed good linear relationship with r > 0.999 in the concentration-ranges of 0.2-2 mg mL-1 and 2.5-20 μg band-1 for WGO by HPLC and HPTLC methods, respectively, and 0.4-10 mg mL-1 and 25-200 μg band-1 for FO by HPLC and HPTLC methods, respectively. The methods were validated, showed good analytical performance and were successfully applied for the analysis of pharmaceutical formulations and synthetic mixtures of the analytes with good recoveries. Therefore, the two methods could be conveniently adopted for routine analysis of similar products in quality control laboratories of pharmaceutical industries especially that simultaneous determination of FO-WGO mixture has not been reported previously. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2017-09-28

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

76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0... wholly owned subsidiary of Pfizer, Inc., 235 East 42d St., New York, NY 10017 has informed FDA that it...-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine AGENCY...

Dissolution testing of orally disintegrating tablets.

PubMed

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

2012-07-01

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

QR encoded smart oral dosage forms by inkjet printing.

PubMed

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.

Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives

NASA Astrophysics Data System (ADS)

Merey, Hanan A.; El-Mosallamy, Sally S.; Hassan, Nagiba Y.; El-Zeany, Badr A.

2016-05-01

Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00 μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p = 0.05.

Comparative drug release measurements in limited amounts of liquid: a suppository formulation study.

PubMed

Welch, Ken; Ek, Ragnar; Strømme, Maria

2006-07-01

A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.

Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

PubMed

Stops, Frances; Fell, John T; Collett, John H; Martini, Luigi G

2008-02-28

Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

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

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method.

PubMed

Homar, Miha; Suligoj, Dasa; Gasperlin, Mirjana

2007-02-01

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.

Green approach towards the determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

PubMed

Mumtaz, Amina; Hussain, Shahid; Yasir, Muhammad

2014-09-01

A simple eco-friendly method has been developed for detection of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms. Both conventional system and microwave assisted procedures are used for the development of color. The blue coloured complex is measured spectrophotometrically at 750nm. Peak shift in FT-IR spectra also indicated the formation of complex. The reaction obeys Beer's law over the concentration range of 50- 250βg/mL of hydroxyzine dihydrochloride. The precision value (intra-day and inter-day RSD) for the drug is not greater than 0.79% and recoveries were found to be in range of 99.01-99.99%. The designed method is applicable for periodic determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

Biopharmaceutical Evaluation and CMC Aspects of Oral Modified Release Formulations.

PubMed

Chang, Rong-Kun; Mathias, Neil; Hussain, Munir A

2017-09-01

This article discusses the range of outcomes from biopharmaceutical studies of specific modified release (MR) product examples in preclinical models and humans. It touches upon five major biopharmaceutical areas for MR drug products: (1) evidence for regional permeability throughout the GI tract, (2) susceptibility to food-effect, (3) susceptibility to pH-effect, (4) impact of chronopharmacology in designing MR products, and (5) implications to narrow therapeutic index products. Robust bioperformance requires that product quality is met through a thorough understanding of the appropriate critical quality attributes that ensure reliable and robust manufacture of a MR dosage form. The quality-by-design (QbD) aspects of MR dosage form design and development are discussed with the emphasis on the regulatory view of the data required to support dosage form development.

Article with buffer layer and method of making the same

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCamy, James W.; Ma, Zhixun; Kabagambe, Benjamin

A method of forming a coating layer on a glass substrate in a glass manufacturing process includes: providing a first coating precursor material for a selected coating layer composition to at least one multislot coater to form a first coating region of the selected coating layer; and providing a second coating precursor material for the selected coating layer composition to the multislot coater to form a second coating region of the selected coating layer over the first region. The first coating precursor material is different than the second precursor coating material.

Solid oral forms availability in children: a cost saving investigation

PubMed Central

Lajoinie, Audrey; Henin, Emilie; Kassai, Behrouz; Terry, David

2014-01-01

Aim To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. Method Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. Results Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). Conclusion Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules. PMID:24965935

Iron crystallization in a fluidized-bed Fenton process.

PubMed

Boonrattanakij, Nonglak; Lu, Ming-Chun; Anotai, Jin

2011-05-01

The mechanisms of iron precipitation and crystallization in a fluidized-bed reactor were investigated. Within the typical Fenton's reagent dosage and pH range, ferric ions as a product from ferrous ion oxidation would be supersaturated and would subsequently precipitate out in the form of ferric hydroxide after the initiation of the Fenton reaction. These precipitates would simultaneously crystallize onto solid particles in a fluidized-bed Fenton reactor if the precipitation proceeded toward heterogeneous nucleation. The heterogeneous crystallization rate was controlled by the fluidized material type and the aging/ripening period of the crystallites. Iron crystallization onto the construction sand was faster than onto SiO(2), although the iron removal efficiencies at 180 min, which was principally controlled by iron hydroxide solubility, were comparable. To achieve a high iron removal rate, fluidized materials have to be present at the beginning of the Fenton reaction. Organic intermediates that can form ferro-complexes, particularly volatile fatty acids, can significantly increase ferric ion solubility, hence reducing the crystallization performance. Therefore, the fluidized-bed Fenton process will achieve exceptional performance with respect to both organic pollutant removal and iron removal if it is operated with the goal of complete mineralization. Crystallized iron on the fluidized media could slightly retard the successive crystallization rate; thus, it is necessary to continuously replace a portion of the iron-coated bed with fresh media to maintain iron removal performance. The iron-coated construction sand also had a catalytic property, though was less than those of commercial goethite. Copyright © 2011 Elsevier Ltd. All rights reserved.

Forming Refractory Insulation On Copper Wire

NASA Technical Reports Server (NTRS)

Setlock, J.; Roberts, G.

1995-01-01

Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

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

PubMed

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 (CV<3.81%, error<3.20%). Good agreement between the found andadded concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.

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

PubMed

Brown, Teagan L; Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J; Tucci, Joseph

2018-02-26

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.

Practical issues of hyperspectral imaging analysis of solid dosage forms.

PubMed

Amigo, José Manuel

2010-09-01

Hyperspectral imaging techniques have widely demonstrated their usefulness in different areas of interest in pharmaceutical research during the last decade. In particular, middle infrared, near infrared, and Raman methods have gained special relevance. This rapid increase has been promoted by the capability of hyperspectral techniques to provide robust and reliable chemical and spatial information on the distribution of components in pharmaceutical solid dosage forms. Furthermore, the valuable combination of hyperspectral imaging devices with adequate data processing techniques offers the perfect landscape for developing new methods for scanning and analyzing surfaces. Nevertheless, the instrumentation and subsequent data analysis are not exempt from issues that must be thoughtfully considered. This paper describes and discusses the main advantages and drawbacks of the measurements and data analysis of hyperspectral imaging techniques in the development of solid dosage forms.

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

PubMed Central

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

Pharmacokinetics of orally administered DL-α-lipoic acid in dogs.

PubMed

Zicker, Steven C; Avila, Albert; Joshi, Dinesh K; Gross, Kathy L

2010-11-01

To determine the pharmacokinetics of DL-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. 27 clinically normal Beagles. In a 3 × 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. Values for pharmacokinetic parameters of orally administered DL-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status.

Calcium hydroxide coating on highly reactive nanoscale zero-valent iron for in situ remediation application.

PubMed

Wei, Cai-Jie; Xie, Yue-Feng; Wang, Xiao-Mao; Li, Xiao-Yan

2018-05-23

Nano scale zero-valent iron (nZVI), a promising engineering technology for in situ remediation, has been greatly limited by quick self-corrosion and low mobility in porous media. Highly reactive nZVI particles produced from the borohydride reduction method were enclosed in a releasable Ca(OH) 2 layer by the chemical deposition method. The amount of Ca(OH) 2 coated on nZVI surface were well controlled by the precursor dosage. At moderate Ca(OH) 2 dosage (R Ca/TFe  = 0.25) condition, the increment of Fe 0 content for the obtained nZVI/Ca-0.25 sample was observed. The interfacial reactions between the iron oxide shell and the Ca(OH) 2 saturated environment were delicately elucidated by the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) spectrum. And the coverage of Ca(OH) 2 shell on spherical nZVI surface was found more complete and uniform for the nZVI/Ca sample obtained from the moderate precursor dosage condition (R Ca/TFe  = 0.25). The Ca(OH) 2 shell before dissolution was demonstrated owning the anti-corrosion capability to slow down the oxidation of Fe 0 core in air, during ethanol storage and in aqueous environment. The mechanism of anti-corrosion capability for nZVI/Ca-0.25 particle was interestingly found to be attributed to the Ca(OH) 2 shell isolation and also be potentially due to the iron oxide shell phase transformation mediated by the outer Ca(OH) 2 shell. An improved trichloroethylene reduction performance was observed for nZVI/Ca-0.25 than bare nZVI. The mobility of nZVI/Ca particles in water-saturated porous media was moderately improved before shell dissolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

Confectionery-based dose forms.

PubMed

Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

2015-01-01

Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

General public knowledge, preferred dosage forms, and beliefs toward medicines in western Saudi Arabia.

PubMed

Alhaddad, Mahmoud S; Abdallah, Qasem M; Alshakhsheer, Sami M; Alosaimi, Salman B; Althmali, Ahmed R; Alahmari, Solaiman A

2014-06-01

To measure general public knowledge, source of knowledge, preferred dosage forms, and beliefs toward medicines. A cross-sectional study design using convenience-sampling technique was used. A pre-validated questionnaire was designed and distributed to the general public through face-to-face interviews. All data were analyzed, and p-values less than 0.05 were considered significant. The study took place in the Clinical Pharmacy Department, Taif University, Taif, Kingdom of Saudi Arabia between August 2012 and February 2013 RESULTS: Nine hundred participants successfully responded to this study. Males represented two-thirds of the respondents (66.8%). In addition, 52% of respondents were of high education level. Modern (74.2%) and alternative medicines (88.7%) were understood by most respondents. Tablets (69.6%) and capsules (37.6%) represented the highest preferred dosage forms. In addition, physicians (66.6%) and pharmacists (46.2%) were the main sources of information regarding medicines. In terms of beliefs, respondents showed wrong beliefs in many statements used in this study. There is a need to improve public knowledge and beliefs toward medicines as well as utilizing public preferred dosage forms. In addition, pharmacists should play a major role in these programs since they are experts on medicines and play a more active role in patient education and counseling.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.

PubMed

Petruševska, Marija; Berglez, Sandra; Krisch, Igor; Legen, Igor; Megušar, Klara; Peternel, Luka; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Mehta, Mehul; Polli, James E; Shah, Vinod P; Dressman, Jennifer

2015-09-01

Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Gastric emptying of multi-particulate dosage forms.

PubMed

Newton, J Michael

2010-08-16

The evidence in the literature for the concept that multi-particulate dosage forms below a specific size empty from the stomach as if they were liquids and hence have the potential to provide the best solution to the formulation of controlled release oral dosage forms, has been considered. There is some evidence that particles less than 1.0mm provide a more rapid response than larger size particles but there is also evidence that this is not always the case and that rapid and reproducible gastric emptying of small particles does not always occur when they are administered. There is strong evidence that food can delay the gastric emptying of multi-particulate systems. Some of the misconception for gastric emptying performance of multi-particulate system is shown to be related to the limitation of the study design and limitation of the way the data is processed. Nevertheless, there is clear evidence that multi-particulate systems can provide effective oral controlled release dosage forms. There is still some way to go with experimental techniques which would allow a definitive answer to the issue of how the variability of the gastric emptying of multi-particulate systems of less than 2.0mm arises. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

PubMed

Kawakami, Kohsaku

2009-09-01

Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

Method of coating metal surfaces to form protective metal coating thereon

DOEpatents

Krikorian, Oscar H.; Curtis, Paul G.

1992-01-01

A process is disclosed for forming a protective metal coating on a metal surface using a flux consisting of an alkali metal fluoride, an alkaline earth metal fluoride, an alkali metal fluoaluminate, an alkali metal fluosilicate, and mixtures thereof. The flux, in particulate form, is mixed with particles of a metal coating material which may comprise aluminum, chromium, mixtures thereof, and alloys containing at least 50 wt. % aluminum and the particulate mixture is applied to the metal surface in a single step, followed by heating the coated metal surface to a temperature sufficient to cause the metal coating material to react with the metal surface to form a protective reaction product in the form of a metal coating bonded to the metal surface. The metal surface which reacts with the metal coating material to form the protective coating may comprise Fe, Co, Ni, Ti, V, Cr, Mn, Zr, Nb, Mo, Tc, Hf, Ta, W, Re and alloys thereof.

Method of coating metal surfaces to form protective metal coating thereon

DOEpatents

Krikorian, O.H.; Curtis, P.G.

1992-03-31

A process is disclosed for forming a protective metal coating on a metal surface using a flux consisting of an alkali metal fluoride, an alkaline earth metal fluoride, an alkali metal fluoaluminate, an alkali metal fluosilicate, and mixtures thereof. The flux, in particulate form, is mixed with particles of a metal coating material which may comprise aluminum, chromium, mixtures thereof, and alloys containing at least 50 wt. % aluminum and the particulate mixture is applied to the metal surface in a single step, followed by heating the coated metal surface to a temperature sufficient to cause the metal coating material to react with the metal surface to form a protective reaction product in the form of a metal coating bonded to the metal surface. The metal surface which reacts with the metal coating material to form the protective coating may comprise Fe, Co, Ni, Ti, V, Cr, Mn, Zr, Nb, Mo, Tc, Hf, Ta, W, Re and alloys thereof. 1 figure.

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

PubMed

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 (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, 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.

Stability of pharmaceutical salts in solid oral dosage forms.

PubMed

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.

Quantitative analysis of perfumes in talcum powder by using headspace sorptive extraction.

PubMed

Ng, Khim Hui; Heng, Audrey; Osborne, Murray

2012-03-01

Quantitative analysis of perfume dosage in talcum powder has been a challenge due to interference of the matrix and has so far not been widely reported. In this study, headspace sorptive extraction (HSSE) was validated as a solventless sample preparation method for the extraction and enrichment of perfume raw materials from talcum powder. Sample enrichment is performed on a thick film of poly(dimethylsiloxane) (PDMS) coated onto a magnetic stir bar incorporated in a glass jacket. Sampling is done by placing the PDMS stir bar in the headspace vial by using a holder. The stir bar is then thermally desorbed online with capillary gas chromatography-mass spectrometry. The HSSE method is based on the same principles as headspace solid-phase microextraction (HS-SPME). Nevertheless, a relatively larger amount of extracting phase is coated on the stir bar as compared to SPME. Sample amount and extraction time were optimized in this study. The method has shown good repeatability (with relative standard deviation no higher than 12.5%) and excellent linearity with correlation coefficients above 0.99 for all analytes. The method was also successfully applied in the quantitative analysis of talcum powder spiked with perfume at different dosages. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

2013-01-01

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 (CV<3.81%, error<3.20%). Good agreement between the found and added concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form. PMID:23575006

Simultaneous quantitative analysis of olmesartan, amlodipine and hydrochlorothiazide in their combined dosage form utilizing classical and alternating least squares based chemometric methods.

PubMed

Darwish, Hany W; Bakheit, Ahmed H; Abdelhameed, Ali S

2016-03-01

Simultaneous spectrophotometric analysis of a multi-component dosage form of olmesartan, amlodipine and hydrochlorothiazide used for the treatment of hypertension has been carried out using various chemometric methods. Multivariate calibration methods include classical least squares (CLS) executed by net analyte processing (NAP-CLS), orthogonal signal correction (OSC-CLS) and direct orthogonal signal correction (DOSC-CLS) in addition to multivariate curve resolution-alternating least squares (MCR-ALS). Results demonstrated the efficiency of the proposed methods as quantitative tools of analysis as well as their qualitative capability. The three analytes were determined precisely using the aforementioned methods in an external data set and in a dosage form after optimization of experimental conditions. Finally, the efficiency of the models was validated via comparison with the partial least squares (PLS) method in terms of accuracy and precision.

Artificial neural networks in evaluation and optimization of modified release solid dosage forms.

PubMed

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-10-18

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.

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

PubMed Central

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-01-01

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. PMID:24300369

Mucoadhesive drug delivery systems

PubMed Central

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials.

PubMed

Gottwald-Hostalek, Ulrike; Uhl, Wolfgang; Wolna, Peter; Kahaly, George J

2017-02-01

Small levothyroxine (L-T4) dose changes can lead to significant clinical effects. To ensure thyroid hormone levels are safely maintained, authorities are increasingly adopting stricter potency specifications for L-T4, the most stringent of these being 95-105% of the labeled dose over the whole shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Lévothyrox ) has been reformulated, and two studies performed, to ensure bioequivalence to the currently marketed formulation and dosage form proportionality of the new formulation. The bioequivalence study was an open-label, randomized, single-dose, two-period, two-sequence crossover comparing the highest dosage strengths of the currently marketed and the new L-T4 formulation at a total dose of 600 μg. The dosage form proportionality study was an open-label, randomized, three-period, six-sequence crossover, comparing 50 μg, 100 μg, and 200 μg L-T4 tablets, at a total dose of 600 μg. Blood samples were taken at predefined time intervals. Primary outcomes were area under the curve (AUC) and maximum concentration (C max ) of thyroxine (T4) in plasma. In the bioequivalence study, comparing the T4 profiles for the new and current formulation of L-T4, the geometric least square mean ratio of the baseline-adjusted AUC 0-72,adj was 99.3% (90% confidence interval [CI]: 95.6-103.2) and the C max,adj was 101.7% (90% CI: 98.8-104.6). Bioequivalence was established if the 90% CI lay within the predefined 0.9-1.11 limits. In the dosage form proportionality study, pairwise comparisons ranged from 99.3% to 104.8%, and all 95% CIs were within the predefined CI range (0.8-1.25): the three dose strengths were dosage form proportional. The new formulation of L-T4 meets the most stringent potency specification guidelines, and has been demonstrated to be bioequivalent to the current formulation and to show dosage form proportionality. The new formulation will enable patients to receive a dose fine tuned to their medical needs, contributing to improved safety in the use of L-T4.

Thermal barrier coating for alloy systems

DOEpatents

Seals, Roland D.; White, Rickey L.; Dinwiddie, Ralph B.

2000-01-01

An alloy substrate is protected by a thermal barrier coating formed from a layer of metallic bond coat and a top coat formed from generally hollow ceramic particles dispersed in a matrix bonded to the bond coat.

[Application characteristics and situation analysis of volatile oils in database of Chinese patent medicine].

PubMed

Wang, Sai-Jun; Wu, Zhen-Feng; Yang, Ming; Wang, Ya-Qi; Hu, Peng-Yi; Jie, Xiao-Lu; Han, Fei; Wang, Fang

2014-09-01

Aromatic traditional Chinese medicines have a long history in China, with wide varieties. Volatile oils are active ingredients extracted from aromatic herbal medicines, which usually contain tens or hundreds of ingredients, with many biological activities. Therefore, volatile oils are often used in combined prescriptions and made into various efficient preparations for oral administration or external use. Based on the sources from the database of Newly Edited National Chinese Traditional Patent Medicines (the second edition), the author selected 266 Chinese patent medicines containing volatile oils in this paper, and then established an information sheet covering such items as name, dosage, dosage form, specification and usage, and main functions. Subsequently, on the basis of the multidisciplinary knowledge of pharmaceutics, traditional Chinese pharmacology and basic theory of traditional Chinese medicine, efforts were also made in the statistics of the dosage form and usage, variety of volatile oils and main functions, as well as the status analysis on volatile oils in terms of the dosage form development, prescription development, drug instruction and quality control, in order to lay a foundation for the further exploration of the market development situations of volatile oils and the future development orientation.

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

PubMed

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.

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

PubMed

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

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

Oesophageal bioadhesion of sodium alginate suspensions 2. Suspension behaviour on oesophageal mucosa.

PubMed

Richardson, J Craig; Dettmar, Peter W; Hampson, Frank C; Melia, Colin D

2005-01-01

Sodium alginate suspensions in a range of water miscible vehicles were investigated as novel bioadhesive liquids for targeting the oesophageal mucosa. Such a dosage form might be utilised to coat the oesophageal surface and provide a protective barrier against gastric reflux, or to deliver therapeutic agents site-specifically. Alginate suspensions swelled and formed an adherent viscous layer on contact with the mucosa. The swelling kinetics of alginate particles on the oesophageal surface was examined with respect to vehicle composition and related to the extent, duration and location of bioadhesion within the oesophagus. Mucosal retention was evaluated in two in vitro models utilising tissue immersion and a peristaltic tube. By varying the vehicle composition it was possible to modulate the rate of swelling of alginate particles on the mucosa and the mucosal retention of suspensions. Suspensions containing predominantly glycerol exhibited superior retention and were preferentially retained within the lower oesophagus. The propensity of these suspensions to rapidly swell on the mucosa and establish adhesive/cohesive bonds may explain their enhanced retention. The potential to control, through vehicle composition, the extent, duration and location of oesophageal retention could provide a useful tool for site targeting of viscous polymers to the oesophagus.

21 CFR 520.1468 - Naproxen granules.

Code of Federal Regulations, 2010 CFR

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... 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...

In vivo Raman measurement of levofloxacin lactate in blood using a nanoparticle-coated optical fiber probe

PubMed Central

Liu, Shupeng; Rong, Ming; Zhang, Heng; Chen, Na; Pang, Fufei; Chen, Zhenyi; Wang, Tingyun; Yan, Jianshe

2016-01-01

Monitoring drug concentrations in vivo is very useful for adjusting a drug dosage during treatment and for drug research. Specifically, cutting-edge “on-line” drug research relies on knowing how drugs are metabolized or how they interact with the blood in real-time. Thus, this study explored performing in vivo Raman measurements of the model drug levofloxacin lactate in the blood using a nanoparticle-coated optical fiber probe (optical fiber nano-probe). The results show that we were able to measure real-time changes in the blood concentration of levofloxacin lactate, suggesting that this technique could be helpful for performing drug analyses and drug monitoring in a clinical setting without repeatedly withdrawing blood from patients. PMID:27231590

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

NASA Astrophysics Data System (ADS)

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.

Spectrophotometric simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form.

PubMed

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 231nm (minima) and 260nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Accelerated aging: prediction of chemical stability of pharmaceuticals.

PubMed

Waterman, Kenneth C; Adami, Roger C

2005-04-11

Methods of rapidly and accurately assessing the chemical stability of pharmaceutical dosage forms are reviewed with respect to the major degradation mechanisms generally observed in pharmaceutical development. Methods are discussed, with the appropriate caveats, for accelerated aging of liquid and solid dosage forms, including small and large molecule active pharmaceutical ingredients. In particular, this review covers general thermal methods, as well as accelerated aging methods appropriate to oxidation, hydrolysis, reaction with reactive excipient impurities, photolysis and protein denaturation.

Development of Oromucosal Dosage Forms by Combining Electrospinning and Inkjet Printing.

PubMed

Palo, Mirja; Kogermann, Karin; Laidmäe, Ivo; Meos, Andres; Preis, Maren; Heinämäki, Jyrki; Sandler, Niklas

2017-03-06

Printing technology has been shown to enable flexible fabrication of solid dosage forms for personalized drug therapy. Several methods can be applied for tailoring the properties of the printed pharmaceuticals. In this study, the use of electrospun fibrous substrates in the fabrication of inkjet-printed dosage forms was investigated. A single-drug formulation with lidocaine hydrochloride (LH) and a combination drug system containing LH and piroxicam (PRX) for oromucosal administration were prepared. The LH was deposited on the electrospun and cross-linked gelatin substrates by inkjet printing, whereas PRX was incorporated within the substrate fibers during electrospinning. The solid state analysis of the electrospun substrates showed that PRX was in an amorphous state within the fibers. Furthermore, the results indicated the entrapment and solidification of the dissolved LH within the fibrous gelatin matrix. The printed drug amount (2-3 mg) was in good correlation with the theoretical dose calculated based on the printing parameters. However, a noticeable degradation of the printed LH was detected after a few months. An immediate release (over 85% drug release after 8 min) of both drugs from the printed dosage forms was observed. In conclusion, the prepared electrospun gelatin scaffolds were shown to be suitable substrates for inkjet printing of oromucosal formulations. The combination of electrospinning and inkjet printing allowed the preparation of a dual drug system.

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

PubMed

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.

Characterisation of pore structures of pharmaceutical tablets: A review.

PubMed

Markl, Daniel; Strobel, Alexa; Schlossnikl, Rüdiger; Bøtker, Johan; Bawuah, Prince; Ridgway, Cathy; Rantanen, Jukka; Rades, Thomas; Gane, Patrick; Peiponen, Kai-Erik; Zeitler, J Axel

2018-03-01

Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging.

PubMed

Markl, Daniel; Zeitler, J Axel; Rasch, Cecilie; Michaelsen, Maria Høtoft; Müllertz, Anette; Rantanen, Jukka; Rades, Thomas; Bøtker, Johan

2017-05-01

A 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI). Printing was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined. A clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3). The 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.

Comparative plasma salicylate and urine salicylurate levels following administration of aspirin, magnesium salicylate, and choline magnesium trisalicylate.

PubMed

Mason, W D

1980-11-01

Eighteen healthy volunteers were administered single doses of commercially available solid dosage forms of aspirin, magnesium salicylate (I), and choline magnesium trisalicylate (II), equivalent to approximately 500 mg of salicylic acid, in a randomized, complete crossover design. Plasma salicylate and urine salicylurate levels were measured by high-pressure liquid chromatography at frequent intervals following dosing; the resultant profiles, areas under the curve (AUC), and percentages of dose excreted as salicylurate were statistically analyzed by an analysis of variance. The plasma salicylate levels following the two dosage forms containing I and II were virtually identical when corrected for small differences in the dose. The plasma salicylic acid level following aspirin was approximately 10% lower during the 1.5--3.0-hr interval due to a portion of unhydrolyzed aspirin, but the dose-corrected AUC for the products tested did not differ significantly (p < 0.05). During the 24 hr following dosing, 66.5 +/- 12.1 68.4 +/- 7.1, and 60.9 +/- 14.1% of the salicylic acid were excreted as urine salicylurate for aspirin, I, and II, respectively, with no significant difference (p < 0.05). Based on this study, there are no significant differences in the rate and extent of absorption of salicylate following the three dosage forms tested, and the elimination kinetics of salicylic acid are not altered by these dosage forms.

Method of Fabricating Protective Coating for a Crucible with the Coating Having Channels Formed Therein

NASA Technical Reports Server (NTRS)

Grugel, Richard N. (Inventor)

2004-01-01

A method is provided for the fabrication of a protective coating for a crucible with channels being formed in the coating. A material is adhered to the outer wall of the crucible to form a pattern thereon. The outer wall of the crucible along with the pattern of material adhered thereto is next coated with another material. The material used to form the pattern should extend through the outer material coating to define at least one port therein. Next, the crucible with its pattern of material and outer coating material is heated to a temperature of transformation at which the pattern of material is transformed to a fluidic state while the crucible and outer coating material maintain their solid integrity. Such transformation could also be accomplished by using a solvent that causes the pattern of material to dissolve. Finally, the material in its fluidic state is removed via the at least one port formed in the outer material coating thereby leaving channels defined in the coating adjacent the outer wall of the crucible.

Lean production of taste improved lipidic sodium benzoate formulations.

PubMed

Eckert, C; Pein, M; Breitkreutz, J

2014-10-01

Sodium benzoate is a highly soluble orphan drug with unpleasant taste and high daily dose. The aim of this study was to develop a child appropriate, individually dosable, and taste masked dosage form utilizing lipids in melt granulation process and tableting. A saliva resistant coated lipid granule produced by extrusion served as reference product. Low melting hard fat was found to be appropriate as lipid binder in high-shear granulation. The resulting granules were compressed to minitablets without addition of other excipients. Compression to 2mm minitablets decreased the dissolved API amount within the first 2 min of dissolution from 33% to 23%. The Euclidean distances, calculated from electronic tongue measurements, were reduced, indicating an improved taste. The reference product showed a lag time in dissolution, which is desirable for taste masking. Although a lag time was not achieved for the lipidic minitablets, drug release in various food materials was reduced to 2%, assuming a suitable taste masking for oral sodium benzoate administration. Copyright © 2014 Elsevier B.V. All rights reserved.

STUDIES ON THE PATHOGENESIS OF FEVER

PubMed Central

Kaiser, Hans Klaus; Wood, W. Barry

1962-01-01

Determination of the dose-response curve for rabbit leucocytic pyrogen reveals a hyperthermic "ceiling" at which there is a marked insensitivity to dosage. This finding has important implications in relation to the quantitative assay of leucocytic pyrogen. Polymorphonuclear leucocytes separated from normal rabbit blood possess the capacity to produce less than 5 per cent of the pyrogen generated by the same number of rabbit granulocytes collected from acute peritoneal exudates. Blood granulocytes, separated in the cold from the buffy coat, contain no detectable preformed pyrogen. The amount of preformed pyrogen within exudate granulocytes represents but a small fraction of the pyrogen which the cells are capable of generating when incubated in normal saline at 37°C. It is suggested that the active pyrogen is formed from an inactive precursor within the cells. Under the conditions tested, cell fragments of rabbit granulocytes fail to produce endogenous pyrogen. The fact that the production of pyrogen is blocked at 4°C is in keeping with the hypothesis that it involves metabolic reactions within the cell. PMID:14453159

Translating Dosage Compensation to Trisomy 21

PubMed Central

Jiang, Jun; Jing, Yuanchun; Cost, Gregory J.; Chiang, Jen-Chieh; Kolpa, Heather J.; Cotton, Allison M.; Carone, Dawn M.; Carone, Benjamin R.; Shivak, David A.; Guschin, Dmitry Y.; Pearl, Jocelynn R.; Rebar, Edward J.; Byron, Meg; Gregory, Philip D.; Brown, Carolyn J.; Urnov, Fyodor D.; Hall, Lisa L.; Lawrence, Jeanne B.

2013-01-01

Down syndrome (DS) is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21 (Chr21). We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST. Using genome editing with zinc finger nucleases, we targeted a large, inducible XIST transgene into the Chr21 DYRK1A locus, in DS pluripotent stem cells. XIST RNA coats Chr21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a “Chr21 Barr Body.” This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Remarkably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one Chr21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of “chromosome therapy”. PMID:23863942

Mechanistic investigation of drug release from asymmetric membrane tablets: effect of media gradients (osmotic pressure and concentration), and potential coating failures on in vitro release.

PubMed

Am Ende, Mary Tanya; Miller, Lee A

2007-02-01

An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a high fat meal or by the presence of a defect in the coating that could cause a safety concern about dose-dumping. The osmotic and diffusional release mechanisms of the AM tablet were independently shut down such that their individual contribution to the overall drug release was measured. Shut off of osmotic and diffusional release was accomplished by performing dissolution studies into receptor solutions with osmotic pressure above the internal core osmotic pressure and into receptor solutions saturated with drug, respectively. The effect of coating failure modes on in vitro drug release from the AM tablet was assessed through a simulated high-fat meal and by intentionally compromising the coating integrity. The predominant drug release mechanism for the AM tablet was osmotic and accounted for approximately 90-95% of the total release. Osmotic release was shutoff when the receptor media osmotic pressure exceeded 76 atm. Diffusional release of the soluble drug amounted to 5-10% of the total release mechanism. The observed negative in vitro food effect was attributed to the increased osmotic pressure from the high fat meal when compared to the predicted release rates in sucrose media with the same osmotic pressure. This suppression in drug release rate due to a high fat meal is not anticipated to affect in vivo performance of the dosage form, as the rise in pressure is short-lived. Drug release from the AM system studied was determined to be robust to varying and extreme challenge conditions. The conditions investigated included varying pH, agitation rate, media osmotic pressure, media saturated with drug to eliminate the concentration gradient, simulated high fat meal, and intentionally placed film coating defects. Osmotic and diffusional shut off experiments suggest that the mechanism governing drug release is a combination of osmotic and diffusional at approximately 90-95% and 5-10%, respectively. In addition, the coating failure mode studies revealed this formulation and design is not significantly affected by a high fat meal or by an intentionally placed defect in the film coating, and more specifically, did not result in a burst of drug release.

Method for forming hermetic coatings for optical fibers

DOEpatents

Michalske, Terry A.; Rye, Robert R.; Smith, William L.

1993-01-01

A method for forming hermetic coatings on optical fibers by hot filament assisted chemical vapor deposition advantageously produces a desirable coating while maintaining the pristine strength of the pristine fiber. The hermetic coatings may be formed from a variety of substances, such as, for example, boron nitride and carbon.

Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol.

PubMed

Jagdale, Swati C; Sali, Monali S; Barhate, Ajay L; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery of atenolol. The floating-pulsatile concept was applied to increase the gastric residence of the dosage form by having lag phase followed by a burst release. The system was generated which consisted of three different parts: a core tablet, containing the active ingredient; an erodible outer shell; and a top cover buoyant layer. The dry, coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with hydroxypropyl methylcellulose (HPMC) K100 M, citric acid, and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their physical properties in vitro release as well as in vivo behavior. The results showed that K3 (180 mg of HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulation, with lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively. Floating time was controlled by the quantity and composition of the buoyant layer. In-vitro results point out the capability of the system with its prolonged residence of the tablets in the stomach and release of drug after a programmed lag time. This was confirmed by in vivo x-ray technique. The objective of the present work was to develop a floating-pulsatile oral drug delivery system of atenolol with addition of hydroxylpropyl methylcellulose (HPMC) K100 M, HPMC K4 M, and HPMC E15 LV in different ratios with citric acid and sodium bicarbonate as gas-forming agents. The system consist of three different parts: a core tablet, containing the active ingredient; a bottom layer that erodes; and a top cover floating layer. Atenolol, a β-blocker, is prescribed widely in diverse cardiovascular diseases, for example, hypertension, angina pectoris, arrhythmias, and myocardial infarction. Developed formulations were evaluated for their physical properties and vitro release as well as in vivo behavior. The results showed that K3 (180 mg HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulations with the lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively, and were found to be the best choice for manufacturing tablets.

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

21 CFR 522.1081 - Chorionic gonadotropin.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

PubMed

Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

2013-03-01

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

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

PubMed

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 drug. Copyright © 2016 Elsevier B.V. All rights reserved.

Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children.

PubMed

Kersten, E; Barry, A; Klein, S

2016-03-01

Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development.

Transmission electron microscopy of coatings formed by plasma electrolytic oxidation of titanium.

PubMed

Matykina, E; Arrabal, R; Skeldon, P; Thompson, G E

2009-05-01

Transmission electron microscopy and supporting film analyses are used to investigate the changes in composition, morphology and structure of coatings formed on titanium during DC plasma electrolytic oxidation in a calcium- and phosphorus-containing electrolyte. The coatings are of potential interest as bioactive surfaces. The initial barrier film, of mixed amorphous and nanocrystalline structure, formed below the sparking voltage of 180 V, incorporates small amounts of phosphorus and calcium species, with phosphorus confined to the outer approximately 63% of the coating thickness. On commencement of sparking, calcium- and phosphorus-rich amorphous material forms at the coating surface, with local heating promoting crystallization in underlying and adjacent anodic titania. The amorphous material thickens with increased treatment time, comprising almost the whole of the approximately 5.7-microm-thick coating formed at 340 V. At this stage, the coating is approximately 4.4 times thicker than the oxidized titanium, with a near-surface composition of about 12 at.% Ti, 58 at.% O, 19 at.% P and 11 at.% Ca. Further, the amount of titanium consumed in forming the coating is similar to that calculated from the anodizing charge, although there may be non-Faradaic contributions to the coating growth.

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

PubMed

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 in the walls. Copyright © 2017 Elsevier B.V. All rights reserved.

Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects.

PubMed

Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P

2010-09-15

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.

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

PubMed Central

Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.

2010-01-01

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. PMID:20957095

A System for Dosage-Based Functional Genomics in Poplar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

A System for Dosage-Based Functional Genomics in Poplar

DOE PAGES

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.; ...

2015-08-28

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

Coated article and method of making

NASA Technical Reports Server (NTRS)

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2003-01-01

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Coated article and method of making

NASA Technical Reports Server (NTRS)

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2002-01-01

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Optimization of the inter-tablet coating uniformity for an active coating process at lab and pilot scale.

PubMed

Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter

2013-11-30

The objective of this study was to enhance the inter-tablet coating uniformity in an active coating process at lab and pilot scale by statistical design of experiments. The API candesartan cilexetil was applied onto gastrointestinal therapeutic systems containing the API nifedipine to obtain fixed dose combinations of these two drugs with different release profiles. At lab scale, the parameters pan load, pan speed, spray rate and number of spray nozzles were examined. At pilot scale, the parameters pan load, pan speed, spray rate, spray time, and spray pressure were investigated. A low spray rate and a high pan speed improved the coating uniformity at both scales. The number of spray nozzles was identified as the most influential variable at lab scale. With four spray nozzles, the highest CV value was equal to 6.4%, compared to 13.4% obtained with two spray nozzles. The lowest CV of 4.5% obtained with two spray nozzles was further reduced to 2.3% when using four spray nozzles. At pilot scale, CV values between 2.7% and 11.1% were achieved. Since the test of uniformity of dosage units accepts CV values of up to 6.25%, this active coating process is well suited to comply with the pharmacopoeial requirements. Copyright © 2013 Elsevier B.V. All rights reserved.

Tailored on demand anti-coagulant dosing: an in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms.

PubMed

Arafat, Basel; Qinna, Nidal; Cieszynska, Milena; Forbes, Robert T; Alhnan, Mohamed A

2018-04-16

Coumarin therapy has been associated with high levels of inter- and intra-individual variation in the required dose to reach a therapeutic anticoagulation outcome. Therefore, a dynamic system that is able to achieve accurate delivery of a warfarin dose is of significant importance. Here we assess, the ability of 3D printing to fabricate and deliver tailored individualised precision dosing using an in-vitro model. Sodium warfarin loaded filaments were compounded using hot melt extrusion (HME) and further fabricated via fused deposition modelling (FDM) 3D printing to produce capsular-ovoid-shaped dosage forms loaded at 200 and 400 µg dose. The solid dosage forms and comparator warfarin aqueous solutions were administered by oral gavage to Sprague-Dawley rats. In vitro, warfarin release was faster at pH 1.2 in comparison to pH 2. A novel UV imaging approach indicated that the erosion of the methacrylate matrix was at a rate of 16.4 and 15.2 µm/min for horizontal and vertical planes respectively. In vivo, 3D printed forms were as proportionately effective as their comparative solution form in doubling plasma exposure following a doubling of warfarin dose (184% versus 192% respectively). The 3D printed ovoids showed a lower C max of warfarin (1.51 and 3.33 mg/mL versus 2.5 and 6.44 mg/mL) and a longer T max (6 and 3.7 versus 4 and 1.5 h) in comparison to liquid formulation. This work demonstrates for the first time in vivo, the potential of FDM 3D printing to produce a tailored specific dosage form and to accurately titrate coumarin dose response to an individual patient. Copyright © 2018. Published by Elsevier B.V.

The practice and clinical implications of tablet splitting in international health

PubMed Central

Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

2014-01-01

Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

Methods of forming hardened surfaces

DOEpatents

Branagan, Daniel J [Iona, ID

2004-07-27

The invention encompasses a method of forming a metallic coating. A metallic glass coating is formed over a metallic substrate. After formation of the coating, at least a portion of the metallic glass can be converted into a crystalline material having a nanocrystalline grain size. The invention also encompasses metallic coatings comprising metallic glass. Additionally, the invention encompasses metallic coatings comprising crystalline metallic material, with at least some of the crystalline metallic material having a nanocrystalline grain size.

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar].

PubMed

Kaneuchi, Miki; Kohri, Naonori; Senbongi, Kaname; Sakai, Hideo; Iseki, Ken

2005-02-01

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.

Preparation of active 3D film patches via aligned fiber electrohydrodynamic (EHD) printing

NASA Astrophysics Data System (ADS)

Wang, Jun-Chuan; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

2017-03-01

The design, preparation and application of three-dimensional (3D) printed structures have gained appreciable interest in recent times, particularly for drug dosage development. In this study, the electrohydrodynamic (EHD) printing technique was developed to fabricate aligned-fiber antibiotic (tetracycline hydrochloride, TE-HCL) patches using polycaprolactone (PCL), polyvinyl pyrrolidone (PVP) and their composite system (PVP-PCL). Drug loaded 3D patches possessed perfectly aligned fibers giving rise to fibrous strut orientation, variable inter-strut pore size and controlled film width (via layering). The effect of operating parameters on fiber deposition and alignment were explored, and the impact of the film structure, composition and drug loading was evaluated. FTIR demonstrated successful TE-HCL encapsulation in aligned fibers. Patches prepared using PVP and TE-HCL displayed enhanced hydrophobicity. Tensile tests exhibited changes to mechanical properties arising from additive effects. Release of antibiotic from PCL-PVP dosage forms was shown over 5 days and was slower compared to pure PCL or PVP. The printed patch void size also influenced antibiotic release behavior. The EHDA printing technique provides an exciting opportunity to tailor dosage forms in a single-step with minimal excipients and operations. These developments are crucial to meet demands where dosage forms cannot be manufactured rapidly or when a personalized approach is required.

Preparation of active 3D film patches via aligned fiber electrohydrodynamic (EHD) printing

PubMed Central

Wang, Jun-Chuan; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

2017-01-01

The design, preparation and application of three-dimensional (3D) printed structures have gained appreciable interest in recent times, particularly for drug dosage development. In this study, the electrohydrodynamic (EHD) printing technique was developed to fabricate aligned-fiber antibiotic (tetracycline hydrochloride, TE-HCL) patches using polycaprolactone (PCL), polyvinyl pyrrolidone (PVP) and their composite system (PVP-PCL). Drug loaded 3D patches possessed perfectly aligned fibers giving rise to fibrous strut orientation, variable inter-strut pore size and controlled film width (via layering). The effect of operating parameters on fiber deposition and alignment were explored, and the impact of the film structure, composition and drug loading was evaluated. FTIR demonstrated successful TE-HCL encapsulation in aligned fibers. Patches prepared using PVP and TE-HCL displayed enhanced hydrophobicity. Tensile tests exhibited changes to mechanical properties arising from additive effects. Release of antibiotic from PCL-PVP dosage forms was shown over 5 days and was slower compared to pure PCL or PVP. The printed patch void size also influenced antibiotic release behavior. The EHDA printing technique provides an exciting opportunity to tailor dosage forms in a single-step with minimal excipients and operations. These developments are crucial to meet demands where dosage forms cannot be manufactured rapidly or when a personalized approach is required. PMID:28272513

Secondary Electron Emission Yields

NASA Technical Reports Server (NTRS)

Krainsky, I.; Lundin, W.; Gordon, W. L.; Hoffman, R. W.

1981-01-01

The secondary electron emission (SEE) characteristics for a variety of spacecraft materials were determined under UHV conditions using a commercial double pass CMA which permits sequential Auger electron electron spectroscopic analysis of the surface. The transparent conductive coating indium tin oxide (ITO) was examined on Kapton and borosilicate glass and indium oxide on FED Teflon. The total SEE coefficient ranges from 2.5 to 2.6 on as-received surfaces and from 1.5 to 1.6 on Ar(+) sputtered surfaces with 5 nm removed. A cylindrical sample carousel provides normal incidence of the primary beam as well as a multiple Faraday cup measurement of the approximately nA beam currents. Total and true secondary yields are obtained from target current measurements with biasing of the carousel. A primary beam pulsed mode to reduce electron beam dosage and minimize charging of insulating coatings was applied to Mg/F2 coated solar cell covers. Electron beam effects on ITO were found quite important at the current densities necessary to do Auger studies.

Process for microwave sintering boron carbide

DOEpatents

Holcombe, C.E.; Morrow, M.S.

1993-10-12

A method of microwave sintering boron carbide comprises leaching boron carbide powder with an aqueous solution of nitric acid to form a leached boron carbide powder. The leached boron carbide powder is coated with a glassy carbon precursor to form a coated boron carbide powder. The coated boron carbide powder is consolidated in an enclosure of boron nitride particles coated with a layer of glassy carbon within a container for microwave heating to form an enclosed coated boron carbide powder. The enclosed coated boron carbide powder is sintered within the container for microwave heating with microwave energy.

Process for microwave sintering boron carbide

DOEpatents

Holcombe, Cressie E.; Morrow, Marvin S.

1993-01-01

A method of microwave sintering boron carbide comprises leaching boron carbide powder with an aqueous solution of nitric acid to form a leached boron carbide powder. The leached boron carbide powder is coated with a glassy carbon precursor to form a coated boron carbide powder. The coated boron carbide powder is consolidated in an enclosure of boron nitride particles coated with a layer of glassy carbon within a container for microwave heating to form an enclosed coated boron carbide powder. The enclosed coated boron carbide powder is sintered within the container for microwave heating with microwave energy.

Terminology challenges: defining modified release dosage forms in veterinary medicine.

PubMed

Martinez, Marilyn N; Lindquist, Danielle; Modric, Sanja

2010-08-01

Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

WHO expert committee on specifications for pharmaceutical preparations. Fortieth report.

PubMed

2006-01-01

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. The report is complemented by a number of annexes. These include: a list of available International Chemical Reference Substances and International Infrared Spectra; supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms; updated supplementary guidelines on good manufacturing practices for the manufacture of herbal medicines; supplementary guidelines on good manufacturing practices for validation; good distribution practices for pharmaceutical products; a model quality assurance system for procurement agencies (recommendations for quality assurance systems focusing on prequalification of products and manufacturers, purchasing, storage and distribution of pharmaceutical products); multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability; a proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms; and additional guidance for organizations performing in vivo bioequivalence studies.

Formulation and delivery strategies of ibuprofen: challenges and opportunities.

PubMed

Irvine, Jake; Afrose, Afrina; Islam, Nazrul

2018-02-01

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

A review on oral liquid as an emerging technology in controlled drug delivery system.

PubMed

Torne, Sangmesh Raosaheb; Sheela, Angappan; Sarada, N C

2017-12-03

The oral liquid drug delivery system (OLDDS) remains as the primary choice of dosage form, though challenging, for the pharmaceutical scientists. In the last two decades, Oral Liquid Controlled Release (OLCR) formulation has gained a lot of attention because of its advantages over the conventional dosage forms. The world of nanotechnology has paved multiple ways to administer the drug through oral cavity in liquid dosage form with an additional advantage of control over the release. In the current study, the various approaches towards the same have been discussed comprehensively to understand the different mechanisms of OLCR. This review also emphasizes on the existing techniques and the developments that have been made to improve on its efficacy including various formulation related factors. It also provides valuable insights into the role of polymers in the development of OLCR formulation that can be used in the management of Gastroesophageal reflux disease (GERD). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of similarity scoring in the development of oral solid dosage forms.

PubMed

Ferreira, Ana P; Olusanmi, Dolapo; Sprockel, Omar; Abebe, Admassu; Nikfar, Faranak; Tobyn, Mike

2016-12-05

In the oral solid dosage form space, material physical properties have a strong impact on the behaviour of the formulation during processing. The ability to identify materials with similar characteristics (and thus expected to exhibit similar behaviour) within the company's portfolio can help accelerate drug development by enabling early assessment and prediction of potential challenges associated with the powder properties of a new active pharmaceutical ingredient. Such developments will aid the production of robust dosage forms, in an efficient manner. Similarity scoring metrics are widely used in a number of scientific fields. This study proposes a practical implementation of this methodology within pharmaceutical development. The developed similarity metrics is based on the Mahalanobis distance. Scanning electron microscopy was used to confirm morphological similarity between the reference material and the closest matches identified by the metrics proposed. The results show that the metrics proposed are able to successfully identify material with similar physical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Pyrocatechol violet in pharmaceutical analysis. Part I. A spectrophotometric method for the determination of some beta-lactam antibiotics in pure and in pharmaceutical dosage forms.

PubMed

Amin, A S

2001-03-01

A fairly sensitive, simple and rapid spectrophotometric method for the determination of some beta-lactam antibiotics, namely ampicillin (Amp), amoxycillin (Amox), 6-aminopenicillanic acid (6APA), cloxacillin (Clox), dicloxacillin (Diclox) and flucloxacillin sodium (Fluclox) in bulk samples and in pharmaceutical dosage forms is described. The proposed method involves the use of pyrocatechol violet as a chromogenic reagent. These drugs produce a reddish brown coloured ion pair with absorption maximum at 604, 641, 645, 604, 649 and 641 nm for Amp, Amox, 6APA, Clox, Diclox and Flucolx, respectively. The colours produced obey Beer's law and are suitable for the quantitative determination of the named compounds. The optimization of different experimental conditions is described. The molar ratio of the ion pairs was established and a proposal for the reaction pathway is given. The procedure described was applied successfully to determine the examined drugs in dosage forms and the results obtained were comparable to those obtained with the official methods.

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca.

PubMed

Brown, Teagan L; Petrovski, Steve; Hoyle, Dannielle; Chan, Hiu Tat; Lock, Peter; Tucci, Joseph

2017-01-01

To isolate and characterize bacteriophage lytic for the opportunistic pathogen Klebsiella oxytoca and their formulation into a range of solid dosage forms for in-vitro testing. We report the isolation, genomic and functional characterization of a novel bacteriophage lytic for Klebsiella oxytoca, which does not infect the closely related Klebsiella pneumoniae. This bacteriophage was formulated into suppositories and troches and shown to be released and lyse underlying Klebsiella oxytoca bacteria in an in-vitro model. These bacteriophage formulations were stable for at least 49 days at 4°C. The successful in-vitro assay of these formulations here suggests that they could potentially be tested in-vivo to determine whether such a therapeutic approach could modulate the gut microbiome, and control Klebsiella oxytoca overgrowth, during antibiotic therapy regimes. This study reports a novel bacteriophage specific for Klebsiella oxytoca which can be formulated into solid dosage forms appropriate for potential delivery in testing as a therapy to modulate gut microbiome during antibiotic therapies.

Spectrophotometric Methods for the Determination of Sitagliptin and Vildagliptin in Bulk and Dosage Forms

PubMed Central

El-Bagary, Ramzia I.; Elkady, Ehab F.; Ayoub, Bassam M.

2011-01-01

Simple, accurate and precise spectrophotometric methods have been developed for the determination of sitagliptin and vildagliptin in bulk and dosage forms. The proposed methods are based on the charge transfer complexes of sitagliptin phosphate and vildagliptin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetrachloro-1,4-benzoquinone (p-chloranil). All the variables were studied to optimize the reactions conditions. For sitagliptin, Beer’s law was obeyed in the concentration ranges of 50-300 μg/ml, 20-120 μg/ml and 100-900 μg/ml with DDQ, TCNQ and p-chloranil, respectively. For vildagliptin, Beer’s law was obeyed in the concentration ranges of 50-300 μg/ml, 10-85 μg/ml and 50-350 μg/ml with DDQ, TCNQ and p-chloranil, respectively. The developed methods were validated and proved to be specific and accurate for the quality control of the cited drugs in pharmaceutical dosage forms. PMID:23675221

The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form

PubMed Central

Szakonyi, Gergely; Zelkó, Romána

2012-01-01

In this paper we give an overview about the interaction of water molecules with pharmaceutical excipients. Most of these excipients are amorphous or partially amorphous polymers and their characteristics are very sensitive to the water content. In the course of the manufacturing processes water sorption is possible, therefore in some cases it is important to strictly control the residual moisture content of a dosage form. There are several mechanisms of water sorption, like water is able to bind to polar groups of hygroscopic excipients and could also exist in the capillary system of amorphous excipients. Several techniques are available to characterise the states of water inside the materials and the effects of residual water on polymers. For this purpose water sorption measurements, differential scanning calorimetry and the Fourier-transform infrared spectroscopy are reviewed. The importance of water content and storage conditions of pharmaceuticals on the properties of the final dosage forms are also demonstrated with practical examples. PMID:23071956

Broadband optical radiation detector

NASA Technical Reports Server (NTRS)

Gupta, A.; Hong, S. D.; Moacanin, J. (Inventor)

1981-01-01

A method and apparatus for detecting optical radiation by optically monitoring temperature changes in a microvolume caused by absorption of the optical radiation to be detected is described. More specifically, a thermal lens forming material is provided which has first and second opposite, substantially parallel surfaces. A reflective coating is formed on the first surface, and a radiation absorbing coating is formed on the reflective coating. Chopped, incoming optical radiation to be detected is directed to irradiate a small portion of the radiation absorbing coating. Heat generated in this small area is conducted to the lens forming material through the reflective coating, thereby raising the temperature of a small portion of the lens forming material and causing a thermal lens to be formed therein.

Aggregation in complex triacylglycerol oils: coarse-grained models, nanophase separation, and predicted x-ray intensities.

PubMed

Quinn, Bonnie; Peyronel, Fernanda; Gordon, Tyler; Marangoni, Alejandro; Hanna, Charles B; Pink, David A

2014-11-19

Triacylglycerols (TAGs) are biologically important molecules which form crystalline nanoplatelets (CNPs) and, ultimately, fat crystal networks in edible oils. Characterizing the self-assembled hierarchies of these networks is important to understanding their functionality and oil binding capacity. We have modelled CNPs in multicomponent oils and studied their aggregation. The oil comprises (a) a liquid component, and (b) components which phase separately on a nano-scale (nano-phase separation) to coat the surfaces of the CNPs impenetrably, either isotropically or anisotropically, with either liquid-like coatings or crystallites, forming a coating of thickness ?. We modelled three cases: (i) liquid?liquid nano-phase separation, (ii) solid?liquid nano-phase separation, with CNPs coated isotropically, and (iii) CNPs coated anisotropically. The models were applied to mixes of tristearin and triolein with fully hydrogenated canola oil, shea butter with high oleic sunflower oil, and cotton seed oil. We performed Monte Carlo simulations, computed structure functions and concluded: (1) three regimes arose: (a) thin coating regime, Δ < 0.0701 u (b) transition regime, 0.0701 u ≤ Δ ≤ 0.0916 u and (c) thick coating regime, Δ > 0.0916 u. (arbitrary units, u) (2) The thin coating regime exhibits 1D TAGwoods, which aggregate, via DLCA/RLCA, into fractal structures which are uniformly distributed in space. (3) In the thick coating regime, for an isotropic coating, TAGwoods are not formed and coated CNPs will not aggregate but will be uniformly distributed in space. For anisotropic coating, TAGwoods can be formed and might form 1D strings but will not form DLCA/RLCA clusters. (4) The regimes are, approximately: thin coating, 0 < Δ < 7.0 nm transition regime, 7.0 < Δ < 9.2 nm and thick coating, Δ > 9.2 nm (5) The minimum minority TAG concentration required to undergo nano-phase separation is, approximately, 0.29% (thin coatings) and 0.94% (thick coatings). Minority components can have substantial effects upon aggregation for concentrations less than 1%.

Method for forming a hardened surface on a substrate

DOEpatents

Branagan, Daniel J [Iona, ID

2008-01-29

The invention encompasses a method of forming a metallic coating. A metallic glass coating is formed over a metallic substrate. After formation of the coating, at least a portion of the metallic glass can be converted into a crystalline material having a nanocrystalline grain size. The invention also encompasses metallic coatings comprising metallic glass. Additionally, the invention encompasses metallic coatings comprising crystalline metallic material, with at least some of the crystalline metallic material having a nanocrystalline grain size.

Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension.

PubMed

Ahad, Abdul; Al-Mohizea, Abdullah Mohammed; Al-Jenoobi, Fahad Ibrahim; Aqil, Mohd

2016-01-01

Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

Prevalence and trends of cellulosics in pharmaceutical dosage forms.

PubMed

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.

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.

PubMed

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.

Solventless visible light-curable coating: I. Critical formulation and processing parameters.

PubMed

Bose, Sagarika; Bogner, Robin H

2010-06-30

Film coating is generally accomplished by spraying polymers dissolved in solvents onto a cascading bed of tablets. The limitations associated with the use of solvents (both aqueous and organic) can be overcome by the use of solventless coating technologies. In this proposed solventless photocurable film coating system, each layer of coating onto the pellets (non-pareil beads) was formed using liquid photocurable monomer, powdered pore-forming agents, photosensitizers and photoinitiators in a mini-coating pan and later cured by visible light. Yield, coating efficiency, variation in color, diameter and roundness were determined for each batch to evaluate process efficiency and coating quality. It was found that the ratio (S/L ratio) of the amount of solid (S) pore-forming agent to volume of liquid (L) monomer, particle size and type of the pore-forming agent, concentration of initiator, and total exposure (light intensity x exposure time) of light were critical formulation and processing parameters for the process. Using lactose as a pore-forming agent, an optimum ratio of pore-forming agent to photocurable polymer was 1.8-3.0 to achieve good process efficiency and uniformity. The ratio was sensitive to particle size and type of pore-forming agent. 2010 Elsevier B.V. All rights reserved.