Zancong Shen1, Samiir Mitragotri. 1. Department of Chemical Engineering, University of California, Santa Barbara 93106, USA.
Abstract
PURPOSE: Oral route offers an attractive mode of drug administration, although its applications are limited by poor stability of peptides and proteins in the gastrointestinal tract. In this article, we report a novel method based on intestinal patches for oral drug delivery. This method involves the use of millimeter size mucoadhesive patches that adhere to the intestinal wall and direct solute diffusion towards the wall similar to that observed in the case of a transdermal patch. METHODS: Intestinal patches were prepared by sandwiching a film of cross-linked bovine serum albumin microspheres between a film of ethyl cellulose and Carbopol/pectin. Delivery of three model drugs, sulforhodamine B. phenol red, and dextran was assessed in vitro using rat intestine. RESULTS: In vitro tests confirmed substantial unidirectional diffusion of model drugs from the patch across the intestinal wall. The presence of ethyl cellulose layer minimized release from the edges as well as from the back side of the patch into the intestinal lumen. In vitro experiments with rat intestine showed that patches were effective in delivering model drugs across the intestine. Trans-lumenal flux of model drugs from intestinal patches was about 100-fold higher compared to that from a solution due to localization of the solute near the intestinal wall and due to minimization of drug loss into the intestinal lumen. CONCLUSIONS: Intestinal patches offer a novel approach for oral drug delivery.
PURPOSE: Oral route offers an attractive mode of drug administration, although its applications are limited by poor stability of peptides and proteins in the gastrointestinal tract. In this article, we report a novel method based on intestinal patches for oral drug delivery. This method involves the use of millimeter size mucoadhesive patches that adhere to the intestinal wall and direct solute diffusion towards the wall similar to that observed in the case of a transdermal patch. METHODS: Intestinal patches were prepared by sandwiching a film of cross-linked bovine serum albumin microspheres between a film of ethyl cellulose and Carbopol/pectin. Delivery of three model drugs, sulforhodamine B. phenol red, and dextran was assessed in vitro using rat intestine. RESULTS: In vitro tests confirmed substantial unidirectional diffusion of model drugs from the patch across the intestinal wall. The presence of ethyl cellulose layer minimized release from the edges as well as from the back side of the patch into the intestinal lumen. In vitro experiments with rat intestine showed that patches were effective in delivering model drugs across the intestine. Trans-lumenal flux of model drugs from intestinal patches was about 100-fold higher compared to that from a solution due to localization of the solute near the intestinal wall and due to minimization of drug loss into the intestinal lumen. CONCLUSIONS: Intestinal patches offer a novel approach for oral drug delivery.
Authors: E Mathiowitz; J S Jacob; Y S Jong; G P Carino; D E Chickering; P Chaturvedi; C A Santos; K Vijayaraghavan; S Montgomery; M Bassett; C Morrell Journal: Nature Date: 1997-03-27 Impact factor: 49.962