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Purpose. We report on the development of a novel controlled-release gastric retention system, which consists of a matrix tablet, coated with a permeable membrane. When immersed in simulated gastric fluid, the tablet expands. The tablet remains expanded for eighteen to twenty hours, during which time the drug is released. The tablet then either disintegrates into fragments or loses its integrity.

To present a novel approach of greatly enhancing aqueous solubility of a model weakly basic drug, haloperidol, by using weak acids that would not form salts with the drug and to attain physically stable form of amorphous drug by drying such aqueous solutions.Aqueous solubility of haloperidol in presence of increasing concentrations of four different weak organic acids (malic, tartaric, citric, fumaric) were determined. Several concentrated aqueous solutions with differing drug-to-acid molar ratios were dried in vacuum oven, and dried materials were characterized by DSC, powder XRD, dissolution testing, and stability study.Acids were selected such that they would not form salts with haloperidol. Haloperidol solubility increased greatly with increased concentrations of malic, tartaric and citric acids, reaching300 mg/g of solution. In contrast to the haloperidol HCl aqueous solubility of 4 mg/g, this may be called supersolubilization. Fumaric acid did not cause such solubilization as it had low water solubility. Dried solids formed dispersions of amorphous haloperidol in acids that were either amorphous or partially crystalline. Amorphous haloperidol was physically stable and had better dissolution rate than HCl salt.A novel method of drug solubilization in aqueous media by acid-base interaction is presented. Physically stable amorphous systems of drugs may also be prepared by using this organic solvent-free approach.

Primary cultures of bovine brain microvessel endothelial cells (BMECs) were used to characterize blood–brain barrier (BBB) uptake and transport of biotin. Both the uptake and the transcellular transport of either radiolabeled or fluorescein-conjugated biotin by confluent monolayers of BMECs were measured. Biotin uptake (K m = 123 µM) and bidirectional transport across BMEC monolayers was a saturable process and could be competed for by unlabeled biotin, biocytin, and biotinmethyl ester. Pantothenic and nonanoic acid were found not to be effective competitors for either biotin uptake or transport. The metabolic inhibitor, 2-deoxyglucose, had only small effects on the saturable apical-to-basolateral transport and apical uptake of biotin by BMECs. In contrast, basolateral-to-apical transport of biotin was substantially attenuated by 2-deoxyglucose pretreatment. Results supported the existence of specific and saturable uptake and efflux carrier systems for biotin in BMEC monolayers. The function of these systems was dependent to some degree on the metabolic status of the BMECs. Our findings confirm the existence of a biotin uptake system at the BBB in vivo and provide the first indication of an efflux system for biotin in BMECs.

We report on the development of a novel controlled-release gastric retention system, which consists of a matrix tablet, coated with a permeable membrane. When immersed in simulated gastric fluid, the tablet expands. The tablet remains expanded for eighteen to twenty hours, during which time the drug is released. The tablet then either disintegrates into fragments or loses its integrity.Tablets containing a soluble drug (chlorpheniramine maleate, i.e., CPM) and a poorly soluble drug (riboflavin 5' phosphate, i.e., R5'P) were compressed. They were coated with a permeable and elastic polymer (Eudragit). Dissolution profiles of these tablets were studied. The changes in the pH, viscosity, and deformation characteristics as a function of time were measured.Carbopol provided a firm structure to the swollen tablet. Polyvinyl pyrrolidone XL (PVP XL) contributed to the swelling of the tablet. Carbonates provided the initial alkaline micro-environment for Carbopol to gel and conferred buoyancy to the tablet. Coating provided the support needed for the core to remain intact during drug release and, at the same time, it allowed drug release due to its permeable nature. During release, the gelling properties of Carbopol lessened, resulting in a decrease in the firmness of the core. This was evident from the decrease in the viscosity of the core. The energy required at 50% strain also decreased as the drug release progressed.When this tablet is ingested, the chances of its elimination through the pylorus should be greatly reduced due to tablet's expansion, and due to its disintegration or loss in integrity it should then be expelled out of the stomach at the end of the drug release.