THE PREPARATION AND EVALUATION OF A SYNTHETIC POLYMERIC, COACERVATED SYSTEM FOR PROLONGED DRUG ACTIVITY WITH EMPHASIS ON FORMULATION FACTORS AFFECTING THE RELEASE OF A SPARINGLY SOLUBLE MEDICINAL AGENT (POLYETHYLENIMINE, POLYVINYLPYRROLIDONE)
Abstract
An investigation was undertaken to study the feasibility of producing a controlled or sustained release drug delivery system by entrapping a solid drug material in an insoluble matrix formed by the interaction of two water-soluble polymeric materials. Ethylene maleic acid (EMA) was interacted with either polyethylenimine (PEI) or polyvinylpyrrolidone (PVP) to form a water insoluble polymeric matrix. N-Acetyl-p-aminophenol (APAP) was chosen as the investigational drug because of its limited water solubility and its relatively short duration of analgesic and antipyretic action as compared to that of aspirin. The granule and tablet systems prepared by the polymeric interactions were evaluated in vitro using dissolution techniques. Granules prepared from the combination of EMA and PEI with the inclusion of APAP were generally insoluble but swelled considerably thus allowing the drug to be released prematurely from the polymer matrix. Attempts to control the swelling by the use of aldehyde-type crosslinking agents and intense heat proved unsuccessful. Interacted polymeric granules of EMA and PVP were prepared and a procedure developed for their optimum preparation. The resultant material was water-insoluble and exhibited a minimum of swelling. An infrared analysis was conducted to substantiate the existence of an interacted system. The dissolution of APAP from the EMA/PVP system revealed only a small delay in the drug dissolution as compared to the EMA/PEI system. Attempts to create a more hydrophobic granule by the incorporation of various amounts of stearic acid met with little success. The addition of ethyl cellulose into the EMA/PVP system was readily accomplished and the dispersal of the cellulosic was achieved through the use of a vacuum desiccator and methylene chloride vapor. Treatment of various granule formulations with organic vapor for different exposure times yielded dissolution patterns for APAP with a significant prolongation of drug availability. Tablets of the EMA/PVP/ethyl cellulose/APAP system were prepared on a hydraulic Carver press using seven different disintegrating agents at concentrations of 10, 20, and 30 per cent of the total tablet weight. These agents included Starch U.S.P., spray-dried lactose, spray-dried acacia, Avicel PH, Nadex 360, Globe 7042, and STA-Rx 1500. The latter three agents are partially water-soluble starches. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.