ABSTRACT
In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1 per cent magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model
Subject(s)
Humans , Acetaminophen/administration & dosage , Cellulose/analogs & derivatives , Acetaminophen/metabolism , Cellulose/administration & dosage , Cellulose/pharmacology , Delayed-Action Preparations , Dose-Response Relationship, Drug , Drug Carriers , Drug CompoundingABSTRACT
To determine whether guinea pigs chronically exposed to morphine would develop tolerance to the morphine-induced contraction of the sphincterof Oddi (SO), adult male guinea pigs were implanted with morphine pellets (100 mg morphine). The effect of increasing IV doses of morphine on the SO was assessed by determining the duration of which saline perfusate stopped flowing into the duodenum of morphine-treated guinea pigs (MTGP) vs monimplanted animals (non-MTGP). Isolated bovine and guinea pigs SO were also challenged with morphine. Int the in vivo experiments the spasmogenic response of the SO from MTGP to morphine was greater than of SO from non-MTGP. However, morphine had no effect on isolated SO. These results indicate that chronic morphine exposure does not results in tolerance of the SO to the spasmogenic effects of morphine. On the contrary, chronic morphine even sensitized the SO to morphine, in addition, the in vitro data indicated that morphine does not act directly on the smooth muscle of SO to cause spasmogenic effect