Bioadhesive polymers as platforms for oral controlled drug delivery III: oral delivery of chlorothiazide using a bioadhesive polymer.
Bioadhesive polymers that bind to the gastric mucin or epithelial cell surface are useful in drug delivery for the purposes of (a) retaining a dosage from in the GI tract and (b) increasing the intimacy and duration of contact of drug with the absorbing membrane. Polycarbophil has previously been shown to have bioadhesive properties in the rat stomach and small intestine and was employed in the present study with a sustained-release delivery system to demonstrate improved drug delivery. Using chlorothiazide as the model drug, drug containing albumin beads were prepared and used as the sustained-release system. The beads were physically mixed with equally sized particles of polycarbophil and placed in a capsule to produce a bioadhesive dosage form. When the dosage form contacts the stomach, the gelatin capsule dissolves, exposing the polycarbophil to the bathing fluid. The bioadhesive polymer rapidly hydrates, retaining the albumin beads and attaching to the mucin coating of the stomach. Plasma drug levels in rats showed a longer duration of action and greater bioavailability for the bioadhesive dosage form than for either albumin beads or drug powder alone. The results suggest that the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.
D000180:Acrylic Resins / Q000378:metabolism; D000284:Administration, Oral; D000418:Albumins / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002740:Chlorothiazide / Q000008:administration & dosage* / Q000378:metabolism; D003692:Delayed-Action Preparations; D004058:Diffusion; D005753:Gastric Mucosa / Q000378:metabolism; D006207:Half-Life; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000180:Acrylic Resins; D000418:Albumins; D003692:Delayed-Action Preparations; D002740:Chlorothiazide; C030312:calcium polycarbophil