Abstract: The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheological and turbidimetric analysis. Films containing 1 mg/cm2 of acyclovir and based on pure HCS and on HCS and PAA mixed in different ratios were prepared by casting technique. The films were subjected to hydration, rheological, mucoadhesion, drug release, “wash away,” and permeation/penetration measurements. A commercial cream containing acyclovir and an aqueous acyclovir suspension were used as references. The addition of PAA to HCS produced a decrease in film hydration. Films based on HCS/PAA weight ratio close to interaction product stoichiometry were characterized by higher rigidity and better “wash away” properties with respect to the other films and the reference formulation. The wors...

Abstract: The purpose of this study was to develop a method of qualitatively predicting the most likely degradants in a formulation or probing specific drug-excipient interactions in a significantly shorter ...

Abstract: This study examines the gastric residence of chitosan microspheres and the local tetracycline concentrations following oral administration in gerbils. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Gastric retention studies were performed by administering radioiodinated [125I] chitosan microsphere suspension in the nonacid-suppressed and acid-suppressed states. At different time points, animals were sacrificed, and the radioactivity in tissues and fluids was measured with a gamma counter. Local tetracycline concentrations were measured using chitosan microspheres loaded with tritiated-[3H]-tetracycline. The radioactivity, measured with a liquid scintillation analyzer, was used to determine the μg of drug per gram of tissues or fluids under nonacid-suppressed and acid-suppressed states. Microspheres with a spherical shape and an average diameter of 2.0–3.0 μm were formed. After 2 hr in the fasted stomach, approximately 10% of the administered dose remained...

Abstract: The objective of this study was to investigate the influence of atomizing air pressure on the coating uniformity and the quality of the film coat. As parameters describing the coating uniformity, the mass variance of the film coated tablets and the variance of the film thickness within a tablet were used. For the examination of the properties of the film coat, the cumulative frequency of the tablet mass, the spray loss, the relative frequency of the film thickness, the minimum amount of polymer required for an enteric coating, and the swelling number were taken into consideration. For this study a Walther Pilot spray gun WA 50 with a liquid orifice diameter of 0.5 mm and a flat jet air cap was used. The experiments were carried out in a Bohle BLC 5 drum coater using four different atomizing air pressures between 0.5 and 2.0 bar. All other parameters were kept constant during the coating process. It could be shown that atomizing air pressure is an important factor influencing the quality and uniformity of a film coat. An increase in the atomizing air pressure will produce smooth tablets with a small mass variance. Due to a greater spray loss, the required minimum amount of polymer for an enteric coating is higher at an atomizing air pressure of 2.0 bar.

Abstract: Matrices made of glyceryl trimyristate as a bioerodible and biocompatible material were manufactured by compression in dimensions that would still allow an application via injection. Pyranine, as a low molecular hydrophilic compound with a low detection limit, and tetramethylrhodamine labeled bovine serum albumin (TAMRA-BSA), as a high molecular weight (66 kDa) protein compound, served as model drugs for release investigations. In vitro studies with pyranine revealed that release depends substantially on the gelatin content of the matrices, which proved to be a useful tool as a release modifier. The duration of the drug release period can be adjusted to a desired time interval ranging from days to weeks by choosing the right gelatin content. Moreover, results illustrated the importance of the molecular weight and the nature of the compound to be incorporated into such matrices, since investigations with TAMRA-BSA showed a more pronounced burst release and altered release profiles and periods. Experiments with hyaluronidase, which served as a model enzyme to assess the problem of protein integrity in such matrices, suggested that proteins may display sufficient stability during the manufacturing procedure of the cylinders or while in contact with the triglyceride matrices. In addition to in vitro investigations, a study in mice revealed that after 15 days of subcutaneous implantation the matrices showed a good in vivo stability. The main conclusion that could be drawn from these results was that triglycerides are a promising alternative to biodegradable polymers for the development of parenteral release systems for protein and peptide drugs.

Abstract: The objective of the present study was to investigate the impact of formulation factors on the properties of a 12h modified-release formulation of verapamil HCl. A 2(3) full factorial design was employed to investigate the influence of amount of Eudragit RS PO/RL PO (X1, a matrixing agent), HPMC K4M (X2, an auxiliary matrixing agent cum binder) and PEG 4000 (X3, channelling agent cum plasticizer). The tablets were prepared by direct compression and they were evaluated for in vitro dissolution studies in 0.1 N HCl. The time required for 90% of the drug release (t90) and similarity factor (f2) were used as responses for the selection of most appropriate batches. Swelling and fluid penetration studies were carried out in 0.1 N HCl. Time required for 90% of the drug release (t90) was calculated by using an appropriate kinetic model for each batch. An ideal drug release profile (i.e., 25% in the first hour and a constant drug release thereafter) was considered as a reference release profile for calculation of f2. Multiple regression analysis was adopted to evolve refined models for t90. The required release pattern was shown by batches containing a low level of Eudragit RS PO/RL PO (30% w/w), low level of HPMC K4M (10% w/w), and high level of PEG 4000 (15% w/w). Response surface plots are shown for t90. These formulations showed slower drug release in alkaline medium (pH 7.2). Succinic acid and KH2PO4 were incorporated in the matrix in order to obtain pH-independent drug release. Swelling of tablets and fluid penetration in the matrix were found to be influenced by the selected independent variables. This study demonstrates that the desired drug release pattern can be obtained by adopting a systematic formulation approach.

Abstract: Laboratory-scale spray-congealing equipment was utilized to fabricate injectable microparticles consisting of polyorthoester and bupivacaine. Operating conditions for the spray-congealing process were optimized to produce microparticles with the desired shape and particle size to yield acceptable syringeability and injectability. Characterizations were performed to determine the chemico-physical properties of polyorthoester before and after microparticle fabrication. Microparticles with different drug loadings and comparable particle sizes were produced, and their in vitro drug-release profiles were determined. The in vitro drug release of microparticles with a high drug loading was markedly faster than those with a low drug loading. This is partially attributed to a more significant initial burst-drug release of the microparticles with a high drug loading. The microparticles have demonstrated the potential to be used for long-acting postsurgery pain management by local injection.

Abstract: A novel approach to derive a compression parameter indicating effective particle deformability.

Abstract: The objective of this investigation was to develop a novel multifunctional coprocessed adjuvant consisting of three known diluents that show different consolidation mechanisms. The method of wet granulation was adopted for the preparation of coprocessed product. Microcrystalline cellulose (MCC) and colloidal silicon dioxide (X1), lactose monohydrate (X2), and dibasic calcium phosphate dihydrate (X3, DCP) were used as independent variables in a simplex lattice design. Croscarmellose sodium was used at 4% level intragranularly in all the batches. The granules (44/120 #) were characterized for angle of repose, bulk density, tapped density, and Carr's index. The tablets of coprocessed adjuvants were characterized for crushing strength, friability, and disintegration time. Multiple linear regression was adopted for evolving refined mathematical models. A checkpoint batch was prepared and evaluated for particle size distribution, moisture uptake, and dilution potential by using nimesulide as a model drug. Microcrystalline cellulose shows poor flowability due to irregular shape and interlocking. Moreover, it loses a part of its compactibility on wet granulation. To attend these problems, a physical blend of 97% microcrystalline cellulose and 3% colloidal silicon dioxide M5 was prepared and used. The blend of MCC and colloidal silicon dioxide showed better flow than that of the original MCC. Hence, it may be easier to mix with lactose and dibasic calcium phosphate. The loss in compactibility of microcrystalline cellulose on wet granulation was also reduced due to presence of colloidal silicon dioxide. As expected, all the batches exhibited acceptable angle of repose (<35 degrees) and quick disintegration (<1 min). Full and refined models for Carr's index and crushing strength were evaluated. Based on the results of grid analysis, a checkpoint (50% MCC, 40% lactose, and 10% DCP) that satisfies both the conditions of Carr's index and crushing strength was selected. The adjuvants absorb very little moisture in the moisture uptake study. The results of dilution potential study reveal that up to 30% nimesulide, a poorly compressible drug, can be incorporated in the coprocessed product. In vitro drug dissolution from capsules containing pure drug powder and compressed tablets was comparable (f2 = 79). The results reveal that the desired product characters can be obtained by varying the quantity of MCC (a ductile material that undergoes plastic deformation), lactose (brittle material with low-fragmentation propensity), and DCP (brittle material with high-fragmentation propensity).

Abstract: The effects of an aqueous film coating process on the morphology and storage stability of hydroxypropyl methylcellulose-coated tablets containing a moisture-labile model drug (acetylsalicylic acid, ASA) were evaluated using an instrumented side-vented tablet pan coater. Coating parameters studied were inlet air absolute humidity 5 g/m3 and 12 g/m3, spraying air pressure 100 kPa and 500 kPa, pan air temperature 35 degrees C and 55 degrees C, and coating solution flow rate 2.2 g/min and 7.8 g/min. The surface roughness of the coatings was measured with a laser profilometer and the chemical hydrolysis of the model drug ASA with an UV-spectrophotometer. The film-coated tablets were stored at 25 degrees C/60% RH and 40 degrees C/75% RH for three months. The high absolute humidity of the inlet air increased the residual water content and surface roughness of the coated tablets. Using a lower coating solution flow rate, higher spraying air pressure and pan temperature the coatings were smooth and homogeneous. In both ambient and accelerated storage conditions, the roughness of the coatings and the hydrolysis of ASA increased, but this was independent of the film coating process. Uniform and smooth hydroxypropyl methylcellulose coatings can be achieved by improved control of process parameters related to the application of the coating solution and water evaporation of the tablet surface.

Abstract: Combinations of Eudragit® RS and deesterified pectin, polygalacturonic acid (PGA), or its potassium and sodium salts, when applied as a film coat, has a potential value as a colon-specific delivery system. Dispersions of PGA in Eudragit RS were used as the film former for coating of 5-aminosalicylic acid (5-ASA) tablet cores. Drug release behavior was assessed, in vitro, under simulating conditions in term of pH and time to in vivo during their transit to the colon. Negligible drug release occurred during first 5 hr where the coated tablets were in the stomach and small intestine. After that, the pectinolytic enzymes were added into the pH 6.8 medium to simulate the in vivo condition where there is the digestion of bacteria in the colon. The release of 5-ASA from the coated tablets occurred linearly as a function of time. Drug release depended on the composition of the mixed film, as well as the ratio of Eudragit RS to PGA or its salts. The highest drug release from the coated tablets of about 40% was obt...

Abstract: The aim of this study was to statistically optimize the use of blends of methacrylic acid ester copolymers with different permeability properties as controlled-release coating systems for tablets to produce predictable predesigned release profiles. A full factorial design was used to study and optimize the use of methacrylic acid ester copolymers Eudragit® RS 30D and Eudragit® RL 30D as coating materials for controlled release. Directly compressed theophylline tablets were coated with aqueous dispersions containing different proportions of the two copolymers using a side-vented coating pan (Accela Cota®). The effect of polymer loading level at 5, 7.5, and 10% weight gain and curing time at 50°C for 12 and 24 hours were also evaluated. Coated tablets were tested for their drug release in water using a United States Pharmacopeia (USP) dissolution apparatus #2. The results showed that increasing the content of the lower permeability copolymer Eudragit® RS 30D, increasing the polymer load, and increasing curi...

Abstract: Purpose. The objective of this study was to investigate the physical stability of micronized powders produced by the spray-freezing into liquid (SFL) particle engineering technology. Materials and Methods. Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 to form a cosolvent solution that was SFL processed. The dried micronized SFL powders were sealed in glass vials with desiccant and exposed to 25°C/60% RH for 3 and 6 mo, 40°C/75% RH for 1, 2, 3, and 6 mo, and conditions where the temperature was cycled between −5 and +40°C (6 cycles/24 hr) with constant 75% RH for 1, 2, 3 and 4 wk. The samples were characterized by using Karl–Fisher titration, differential scanning calorimetry, x-ray diffraction, specific surface area, scanning electron microscopy, and dissolution testing. Results. Micronized SFL powders consisting of porous aggregates with small-particle domains were characterized as having high surface areas and consisted of amorphous danazol embed...

Abstract: In vitro release for topical drug products is carried out using a vertical diffusion cell system and a synthetic support membrane. The improvements in vertical diffusion cell design and automated procedures have been carefully studied and evaluated to establish their reproducibility and ruggedness of the experimental procedure. The data were analyzed using 90% confidence interval procedure developed and published by the US Food and Drug Administration in SUPAC-SS (Start Up and Post Approval Changes-Semi Solid) guidance.

Abstract: Aqueous liquid formulations of efavirenz, a nonnucleoside inhibitor of reverse transcriptase, have prolonged burning (peppery) taste. Medium-chain triglycerides (MCT) was used as the vehicle to mask the taste and obtain palatable oral liquid formulations containing 20 mg/mL efavirenz. The use of MCT for enhancement of palatability and stability is recommended for drugs that show high solubility and partitioning in this vehicle.

Abstract: The objective of this study was to investigate the possible impacts of curing and storage conditions on dissolution of controlled release diphenhydramine HCl pellets coated with EUDRAGIT NE30D. The accumulative percentage of dissolved active drug was used as the response in three statistical experimental design studies: 32 full factorial, Box-Behnken and 2(3) designs. By only considering curing temperature and curing time, both factors were found to significantly affect the dissolution rate, but curing temperature had greater impact than curing time. When considering polymer coating level, curing temperature and curing time together, polymer coating level and curing temperature had important effects on dissolution rate, but curing time became insignificant among these three factors. The addition of the water-soluble additives hydroxypropyl methyl cellulose and mannitol made coating films less sensitive to curing, and there was little or no difference in their effect in the model studied. Lower levels of a water-insoluble additive (kaolin) had little impact on dissolution; however, when the level of water-insoluble additive increased, the coating film became more sensitive to curing, especially at the lower curing temperature of 30 degrees C.

Abstract: Five aluminum phosphate adjuvants having P/Al molar ratios ranging from 0.74 to 0.26 were prepared. The adjuvants were characterized by both protein adsorptive capacity and rate of acid neutralization at pH 2.25, 25°C. The protein adsorptive capacity was not a useful parameter to compare the initial properties of the adjuvants, as differences in surface charge of the adjuvants required the use of different proteins. In contrast, the rate of acid neutralization allowed a comparison of the freshly precipitated adjuvants and revealed that the rate of acid neutralization was directly related to the P/Al molar ratio. The protein adsorptive capacity decreased slightly during 39 weeks of aging at room temperature. The changes in the rate of acid neutralization were much greater and indicated that a P/Al molar ratio of at least 0.5 was required to minimize the aging of the adjuvants. Thus, the rate of acid neutralization was found to be the most sensitive parameter to characterize aluminum phosphate adjuvants.

Abstract: The PLA-b-PEO block copolymers were studied as potential carriers for anti-inflammatory and anticancer drugs. The copolymers were labeled with 125I, and their micelles in physiological saline were prepared by dialysis. Copolymer 1, with Mw=12,360 (PLA/PEO=7000/5000), formed particles of about 300 nm in diameter (Rh was 150 nm), whereas copolymer 2, with Mw=20,470 (6000/14,000), made up micelles of about 72 nm in diameter (Rh was 35.8 nm). Their pharmacokinetic and biodistribution profiles were compared in normal rats and rats with carrageenan-induced inflammation after intravenous application of about 5 mg/kg of each copolymer. Copolymer 2, forming smaller particles, showed longer distribution and elimination half-lives. Both copolymers under study exhibited significantly higher uptake by inflammatory tissue compared with noninflammatory one. The study indicates that PLA-b-PEO copolymers, having different molecular weight of the chains, have similar biological behavior in most organs and tissues. Differen...

Abstract: The study aimed to investigate the effect of triethyl citrate (TEC) plasticizer level (10, 15, and 20%), curing temperature (40, 50, and 60°C) and time (0 to 168h) on the release of a highly lipophilic drug bumetanide from pellets coated with methacrylate ester copolymer (Eudragit RS). Bumetanide was layered onto sugar pellets followed by coating with 6% Eudragit RS with and without hydroxypropyl methyl cellulose (HPMC) seal coat using Wurster Fluid Bed equipment. Coated pellets were stored for 3 months at room temperature and the release was tested in USP purified water. At 10% TEC level, increasing curing time and temperature lead to slower drug release. At 15 and 20% TEC levels, curing initially decreased drug release followed by increase in the release at longer curing time and higher temperature. Drug release from coated pellets plasticized with 15% TEC and completely cured followed zero order kinetic models. At plasticizer level of 20%, bumetanide release from the completely cured pellets was better...

Abstract: Purpose. To compare the physical and physicochemical characteristics of carbamazepine microparticles prepared using two different methods: (1) the rapid expansion of supercritical solutions (RESS) and (2) the spray-drying process. Methods. For both processes, microparticles were produced over a range of different temperatures (35 to 100°C). For the RESS method, carbon dioxide was the solvent used over a pressure range of 2500 to 3500 psi. As for the spray-drying method, different organic solvents were used at atmospheric pressure. Comparison was based on morphology, crystalline structure, mean particle size, and size distribution of processed particles. The influence of process parameters on microparticles' characteristics was also investigated. Particles were analyzed using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC). Results. The carbamazepine particles used as unprocessed starting material had a mean ...

Abstract: The aqueous solubility of guaifenesin, a highly water‐soluble drug, in the presence of salts, sugars, and cosolvents was determined at 25°C and 40°C. The solubility of drug at both temperatures was...

Abstract: The main objective of this study was to optimize the stability of cetyl alcohol/stearyl alcohol emulsions in terms of percentage of internal phase volume, emulsifier type and concentration, and amount of external phase (water). Creams (o/w emulsions) were prepared by phase inversion and physical properties as particle size of the internal phase, apparent viscosity, and sedimentation volume evaluated. Stability was performed at room temperature, 40 degrees C, 50 degrees C, and under stress conditions. High hydrophilic lipophilic balance (HLB) nonionic surfactants as tween 80, tween 20, Myrj 52, Brij 35, and low HLB span 60 were used as emulsifying agents. The percentage of internal phase components (cetyl alcohol and stearyl alcohol), percentage of emulsifying agents, and percentage of aqueous external phase were varied, and stability was investigated. As the level of emulsifier agent (tween 80 and span 60) increased from 3% to 15%, and the percent of the internal phase remained constant at 30%, the particle size of the internal phase decreased and the cream became more stable. Formulations of the same composition, but prepared using Myrj 53 and tween 20 as emulsifiers, showed a larger particle size than formulations prepared using tween 80 and Brij 35. As the level of the internal phase volume increased and consequently the amount of water decreased, emulsion viscosity increased. The best formulation containing 30% internal phase (50% cetyl alcohol, 35% stearyl alcohol), 15% emulsifying agents (tween 80/span 60 ratio of 3:1), and 70% water was selected, and effects of process temperature and cooling rate on emulsion stability investigated. This formulation was further investigated in terms of stability of a 1% hydrocortisone addition by varying the percentage (30%, 35%, 40%, and 45%) of internal phase and percentage of water (70%, 65%, 60%, and 55%). The best formulation contained 45% internal phase (22.5 g cetyl alcohol, 15.75 g stearyl alcohol, 15% emulsifying agent, which is equivalent to 5 g tween 80 and 1.7 g span 60), and 55% w/w water, was manufactured under different manufacturing processes. Emulsions prepared by homogenization at the beginning of the process of emulsification were stable with small internal phase particle diameter. This study demonstrates that at every cetyl alcohol/stearyl alcohol ratio there is a phase volume/emulsifier HLB ratio, which results in optimum stability.

Abstract: An apparatus to dry aqueous dispersions of solid lipid nanoparticles (SLNs) was designed. Optimal running conditions were evaluated to obtain minimum process time and produce dried SLNs characterized by small size variation. To achieve process optimization, SLN average diameter, SLNs polydispersity index, and drying time were related to three operative variables: process temperature, SLN concentration in the original aqueous dispersions, and nitrogen flow rate as the physical means of the drying process. An experimental design procedure and a multicriteria optimization method, targeting desirability functions, enabled us to obtain the optimal conditions for all responses. Drying time, average diameter, and polydispersity index of dried SLN batches were more favorable than those obtained by freeze-drying identical SLN aqueous dispersions with the same initial nanoparticle concentration.

Abstract: Silicified microcrystalline cellulose (SMCC) has physico-mechanical properties that may be of advantage in hard gelatin capsule formulations. The present research was designed to evaluate and compare SMCC's performance to that of other excipients commonly used in hard gelatin capsule direct-fill formulations. All capsules were filled using a fully instrumented Zanasi LZ-64 automatic capsule-filling machine. Four grades of SMCC [SMCC 50, SMCC 90, SMCC HD90, and an experimental-grade (SMCC X)] were investigated. Anhydrous lactose (direct tableting grade), pregelatinized starch (PGS) (Starch 1500), and microcrystalline cellulose (MCC) (Emcocel 90M) were chosen as the control fillers. The following properties were measured: capsule fill weight, relative standard deviation of capsule fill weight, plug ejection force, plug maximum breaking force (MBF), and the dissolution of two marker compounds (acetaminophen and piroxicam). The MBF of capsule plugs increased with increases in compression force from 50N to 100N for all excipients. Starch 1500 and anhydrous lactose plugs exhibited the lowest MBF values. PGS, anhydrous lactose, SMCC HD90, and SMCC X consistently exhibited the lowest ejection forces under the same experimental conditions, this difference being most apparent at higher compression forces. Different patterns were observed in the way compression force affected the fill weight of the materials studied. Overall, there was no clear pattern to the way the relative standard deviation (RSD) of capsule fill weight varied with encapsulation conditions. Sodium stearyl fumarate (SSF) appeared to be somewhat more efficient at reducing the ejection force than magnesium stearate at the same level, this difference being especially apparent at the 14-mm piston height. Formulations containing either 5% piroxicam, 30% acetaminophen, or 50% acetaminophen exhibited faster drug dissolution when MCC or SMCC was the filler than when anhydrous lactose or PGS was the filler. The presence of colloidal silicon dioxide in SMCC did not appear to influence the dissolution of these drugs. The data suggest that SMCC could be a suitable direct-fill excipient for hard shell capsule formulations.

Abstract: The objective of this study was to prepare a combination of immediate release, enteric coated, and controlled release (CR) beads and to mathematically model in vitro drug release characteristics of the combination based on the release profiles of individual beads. Uncoated beads were manufactured by using extrusion/spheronization technology. Fluid-bed bottom spraying was used for coating: Eudragit-L-30D for enteric coating and Eudragit-NE-30D for CR coating. In vitro drug release profiles for uncoated and coated beads were each fitted to appropriate mathematical equations. The drug release from the bead combination dosage form was predicted from the individual mathematical models and verified experimentally in vitro. The in vitro dissolution was conducted in 0.1 N HCl for 2 hr and then in buffer (pH 6.5 phosphate, 0.05 M) to mimic in vivo conditions using USP dissolution apparatus I. The results showed that uncoated beads gave similar release profiles in water, acid, and buffer with complete release withi...

Abstract: The effect of steam sterilization (dwell@121 degrees C) on the apparent viscosity of solutions of carbomer 940P, guar gum, hydroxyethylcellulose (HEC), and xanthan gum was studied. Guar gum and carbomer 940P could be steam sterilized for 30 min without any change in the apparent viscosity. Steam sterilization of HEC and xanthan gum resulted in a substantial decrease in the apparent viscosity and the desirable shear-thinning rheology. The addition of sodium chloride to either polymer prior to steam sterilization diminished the effect of sterilization on the rheology. The apparent viscosity of xanthan solutions was not significantly affected if the solution was made isotonic with sodium chloride (0.15 M). The addition of sodium chloride to xanthan gum after steam sterilization resulted in full recovery of the initial rheological properties. Carbomers, guar gum, and xanthan (in 0.15 M NaCI) are candidates for use in pharmaceutical solutions/suspensions that are subjected to steam sterilization.

Abstract: Salbutamol elementary osmotic pump (EOP) tablets were developed, and fundamental variables affecting their release characteristics were evaluated. The effects of film thickness and compression force on drug release from the tablets containing fixed amount of sodium chloride used as osmogent were evaluated. The core tablets were directly compressed at four compression forces and coated with 3% wt/vol cellulose acetate in acetone to levels of 2%, 3%, and 4% wt/wt. Coated tablets were drilled with CO2 laser beam to form drug delivery orifice of approximately 400 microm in diameter. The drug release was found to follow zero order fashion. The release rate decreased with the increased film thickness and was not affected by the compression force or porosity. The tablets coated to 3% and 4% levels exhibited the release rates within the range calculated from pharmacokinetic data. To illustrate the effect of osmogent content, the tablets were prepared at four osmogent levels and compressed at a constant compression force. The core tablets were coated to a level of 3% wt/wt. The release rate was initially increased with osmogent content and then decreased. At higher osmogent contents, the drug fraction in soluble component was decreased and resulted in the reduction of drug release. In conclusion, film thickness and osmogents played important roles in drug release from EOP tablets.

Abstract: Two strengths of BMS-309403 capsules were developed from a common stock granulation. Dissolution testing of the capsules was conducted utilizing the USP apparatus 2 (paddle) with a neutral pH dissolution medium. Unexpectedly, the lower-strength capsules exhibited slower dissolution than the higher-strength capsules filled with the same stock granulation. Higher variability was also observed for the lower-strength capsules. This was found to be mainly caused by a low fill weight in a relatively large size hard gelatin capsule shell. Instead of bursting open, some gelatin capsule shells softened and collapsed onto the granulation, which delayed the release of the active drug. The problem was aggravated by the use of coil sinkers which hindered the medium flow around the capsules. Switching from the gelatin capsule shells to the HPMC (hydroxypropyl methylcellulose) shells reversed the dissolution rate ranking between the two capsule strengths. However, both dissolved at a slower rate initially than the gelatin capsules due to the inherent dissolution rate of the HPMC shells at pH 6.8. Notably, the HPMC shells did not occlude the granulation as observed with the gelatin shells. The study demonstrated that the dissolution of capsule formulations in neutral pH media was significantly affected by the fill weight, sinker design, and capsule shell type. Careful selection of these parameters is essential to objectively evaluate the in vitro drug release.

Abstract: A novel aqueous coating dispersion of amylose-rich corn starch (Hylon VII) was evaluated in an aqueous film-coating process of tablets using an instrumented laboratory-scale pan-coating apparatus. The influence of two independent process variables, the coating temperature and the atomizing air pressure, on the properties of the coated tablets were investigated. The pre-use stability of aqueous coating dispersion (i.e., amylose corn-starch precipitate) was studied using a powder X-ray diffraction (XRD) technique. The crystallinity of amylose starch in the coating dispersion was found to increase slightly during 9 months of storage (in a refrigerator 6±2°C). The film coatings of an aqueous amylose-rich starch dispersion were successfully applied onto tablets without any significant drawbacks, such as nozzle blockage or related problems. It was found that the temperature in the coating pan had a significant influence on the film surface roughness, mechanical strength, and drug release in vitro. When the lowe...