A DRUG-POLYMER INTERACTED SYSTEM. STABILIZATION AND PROLONGATION OF RELEASE OF AQUEOUS SOLUTIONS (POLYMETHYL VINYL ETHER)
Abstract
Pharmaceutical manufacturers have been keenly interested in improving the pharmacodynamic patterns of drugs by dosage form design, and have stressed prolonged drug release in oral medicaments. Among the numerous methods of altering drug availability to the patient, techniques involving the preparation of stable prolonged action liquid dosage forms have received the least research effort and have produced the least advancement in products of improved design. Liquid prolonged release preparations are generally of the emulsion, suspension or ion exchange type, wherein the drug particle is either coated so as to form a pellet of micron dimension, or is complexed onto the ion exchange resin which is then suspended in a suitable vehicle. The initial phase of this study was concerned with the selection of several non-toxic water soluble polymers which would interact with the insoluble chlorpromazine base. Interaction tendencies were followed by the solubility method of analysis. The interaction of the tertiary amine, chlorpromazine, with the half amide/ammonium salt of poly(methyl vinyl ether/maleic anhydride) resulted in considerable solubilization (2 mg./ml.) of the drug in aqueous media. The drug solubilization occurred in a linear manner with corresponding increases in polymer concentration. The drug-polymer solutions were subsequently evaluated for drug release rate from the interacted system according to equilibrium dialysis and for stability enhancement over aqueous solutions of free chlorpromazine hydrochloride. The dialysis release rate studies were conducted at 37(DEGREES)C. in a rotating bottle assembly. Results showed that the drug-polymer solutions had reproducible delayed diffusion characteristics in artificial gastrointestinal fluids. The effect of increased polymer concentration (2% to 5%) was investigated. Other polymers which substantially increased the solubility of chlorpromazine were; the acrylamide copolymer and the high molecular weight grade of poly(methyl vinyl ether/maleic anhydride). Williamson activity cages were used to determine the duration of in-vivo response (of drug and drug-polymer product in solution) in the rat. The evaluation showed that the drug-polymer solution had a 9.0 hour consistently significant therapeutic response, while the chlorpromazine hydrochloride displayed a 3.5 hour consistently significant duration of drug action. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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