EFFECT OF PROLONGED GASTRIC RETENTION ON THE BIOAVAILABILITY OF MODEL DRUGS ABSORBED BY PASSIVE AND SATURABLE TRANSPORT (POLYMETHYL VINYL ETHER)
Abstract
This investigation was undertaken to study te effect of a controlled diffusion film coating on the bioavailability of model drugs absorbed by passive and saturable transport mechanisma. Poly (methyl vinyl ether/maleic anhydride) copolymer (PVM/MA), crosslinked with various ratios of polyoxyethylene monolaurate, and plasticized with triacetin, was evaluated as controlled diffusion capsule and tablet coatings. Ampicillin was selected as the drug absorbed by passive diffusion whose absorption efficiency appears to be dose independent. A randomized experimental design was used for determining the effects of coating variables on the dissolution release characteristics of coated capsules containing ampicillin trihydrate. In vitro release characteristics studied included dissolution/permeation lag time, the rate and order of drug release and the extent of drug release. The other variables studied were the equilibrium linear swelling ratio and the breaking strength of coated capsules. Ampicillin capsules were coated with two different lots of PVM/MA 169 containing 78 and 100% anhydride. Polymer films containing 78% anhydride produced a more permeable membrane which released the drug at an overall faster rate. No differences were observed within and between lots in terms of the equilibrium linear swelling ratio or the breaking strength of the coated capsules. Some coated capsules were subjected to ammonia gas treatment to improve the reliability of swelling by "poisoning" the potential crosslinking between gelatin of the capsules and the polymer. The swelling characteristics, however, are not materially affected by such treatment and drug release lag time of an hour or more continued to be observed. No enhancement of bioavailability was observed between the coated capsules described above and a commercial uncoated capsule. The feasibility of enhancing the bioavailability of ampicillin trihydrate by gradually metering it into the stomach in solution was studied using a minidosing approach. The approach involved the division of a single drug dose into twenty four equal fractional doses, which were administered at 15 minute intervals. An analog computer simulation study was also run to investigate the effect of modifying the minidosing schedule to further examine the feasibility of enhancing ampicillin bioavailability. No significant enhancement in the bioavailability of ampicillin was found using either the minidosing approach or the computer simulation study. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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