Siew, Lee Foong; (1997) Colon specific delivery of drugs using organic solvent ethylcellulose/amylose systems. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Colonic drug delivery based on amylose/ethylcellulose coatings has been described previously using an aqueous system. The aim of this study was to develop an organic based system which can be used for water sensitive drugs. The coating materials used were organic ethylcellulose solution either in ethanol, propanol or ethyl lactate, blended with aqueous amylose-butanol complex dispersion. Due to the sensitivity of ethylcellulose to the presence of water, the coating materials were initially investigated for their compatibility in different solvent/water compositions. The critical concentration of gelation for each solvent system was determined (74%, 62% and 54% for ethyl lactate, ethanol and propanol respectively). Physical and mechanical properties of the resultant mixed polymeric films cast from different solvent systems were determined, and the structures of the films were visualised in order to assess the potential solvent systems for use in a coating process. In vitro degradation of the free films by faecal bacteria and α-amylase were investigated and shown to be directly related to the amylose content. From these free film studies, it was possible to show how the solid ratios of amylose/ethylcellulose influenced the properties of the resultant films. The site-specific release performance of the systems were assessed using spray-coated pellets containing 5ASA, paracetamol and ephedrine prepared by the process of extrusion/spheronisation. The shape factor of the pellets were assessed using an image analyser and the residual solvent content within the film coats was determined by thermogravimetric analysis. The pellets were subsequently tested in vitro for their dissolution performance. Systems were found to be capable of preventing release in simulated gastric and intestinal fluids. The solid ratio of amylose to ethylcellulose, the coating levels and drug solubilities were found to influence the in vitro drug release. 5ASA pellets coated with ethylcellulose:amylose ratios of 3:2 and 1:1 to coat thicknesses of 10% and 15%TWG respectively were found to show significant higher drug release in the presence of faecal bacteria and commercially available bacterial α-amylase. These systems, therefore, have the potential for colonic delivery for drugs with very low solubility.

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