EVALUATION OF MORPHINE, CODEINE AND D-PROPOXYPHENE IN RATS UTILIZING PHARMACOLOGICAL DATA OBTAINED FROM AN OPTIMIZED ANALGESIA TESTER
Abstract
The applicability of the molecular scale drug entrapment concept for improving the action of morphine, codeine, and d-propoxyphene was investigated. Seven different methods of interacting the analgetic drugs with methacrylate-methacrylic acid copolymer latices were evaluated in vitro and in vivo. For in vivo assessment of the products, drug-polymer interaction and dissolution studies were conducted. Dissolution testing was accomplished using a multi-channel continuous flow apparatus which was standardized by investigating the effects of days, dissolution cells, flow rates, and sample sizes on the release profiles of the products. Subsequently, the apparatus was used to determine the effect of the drug concentration used to prepare a product and the effect of the product's particle size on its release profile. Both effects were found to be influential on a product's in vitro performance. The reslts from the dissolution testing, in agreement with the drug-polymer interaction studies, indicated that the products investigated had an extremely low affinity to interact with the polymer. For in vivo evaluation of the drug-polymer products, a light-beam tail-flick tester was employed. Principles of statistical design and optimization were utilized to increase the reliability and reduce the variability of this thermal technique in evaluating analgetic drugs in test animals (rat tail-flick response). The light-beam technique was compared against the more conventional hot-wire method by in vitro (temperature profiles) and in vivo (analgetic response profiles) evaluations, both of which showed the advantages and superior performance of the former over the latter. The utility of this analgesia tester accompanied by appropriate data collection (reaction time) and response variable expression (response intensity) in reducing the problems associated with data treatment was demonstrated. This analgesia tester was then used to evaluate the drug-polymer interacted systems in vivo. Results showed that the products studied did not offer any prolongation of analgetic activity. The data obtained from the optimized analgesia tester and the standardized dissolution testing procedure corroborated each other and thus resulted in reliable in vitro - in vivo correlations for the drug-polymer interacted systems. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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