PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES OF POLYMERIC LATEX COAGULA AND THEIR USE AS NEW RECTAL DRUG DELIVERY SYSTEMS FOR ANALGETICS (MORPHINE, CODEINE)
Abstract
An evaluation of the pharmacological response produced by selected analgetics administered rectally to rats, was undertaken. The analgesics, morphine and codeine, were dosed in a polyethylene glycol base suppository as the conventional form of the drugs. Codeine was chosen to be administered also as a polymer-drug product. The polymer-drug products prepared by molecular drug entrapment employing the coagulation of methylmethacrylate-methacrylic acid copolymer latices and cellulosic pseduo-latices were evaluated for their effect on the duration of action and effectiveness of codeine. The enhanced action of the polymer drug products was found to correlate with selected physicochemical properties on the rectal bioadhesion and retention of the products. Studies of the pharmacological response produced by morphine or codeine administered rectally to rats showed that both drugs exhibit linear pharmacokinetics. Excellent correlation values were found for the relationship between the average analgetic response intensity at the time of maximum response and the different doses of both analgesics. The methylmethacrylate-methacrylic acid copolymers and the cellulosic polymers-codeine products when rectally administered in a polyethylene glycol suppository base were found to improve the effectiveness of codeine when compared to its analgetic activity from a conventional suppository. The intense and probably undesirable 400 to 500% levels of analgesia and accompanying animal stupor produced by the conventional form of the drug for a relatively short period of time (2 to 3 hours), were substituted by analgetic levels of 100 to 250% uniformly spread over a 5 to 6 hour period of time, by the polymer-drug products. When the polymer-drug products suppositories were subjected to in vitro release studies for codeine, it was found that the per cent of codeine released as a function of time was described by a linear system for the first 4 1/2 hours; while the conventional codeine suppository product was described by a sigmoidal-type shape curve. The in vitro per cent of codeine released from the rectal dosage forms as determined by a membrane enclosed system in a flow cell was found to provide excellent correlation with the in vivo analgetic response intensity for all of the polymer-drug products as well as the conventional drug suppositories. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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