Microencapsulated lipid cores for site-specific delivery of corticosteroid and peptide drugs to the colonic region

Drugs with very different physical and pharmaceutical properties such as the hydrophobic topically acting drug budesonide, or the hydrophilic systemic peptide insulin, were encapsulated in a new microparticulate system intended for a colon-specific drug delivery. These microparticles were designed to provide pH-sensitive and controlled release properties by combining a retarding-release lipid core and a pH-sensitive coating. Lipid cores were prepared with either methods, melt dispersion (budesonide) or solvent evaporation (insulin), and then encapsulated within a pH-sensitive polymer, the hydroxypropylmethylcellulose acetate succinate (HPMC-AS), conveniently adapting the aqueous solvent extraction technique. Encapsulation efficiency and release characteristics of budesonide-loaded cores were mainly influenced by the nature of lipid, glycerol behenate or tetraglycerol pentastearate. It was shown that once the protective pH-sensitive coating dissolved at a pH value approximating 65, the budesonide released itself from the lipid cores following a biphasic profile. Drug diffusion through the pores and channels of the lipid matrix was the probable predominant mechanism in the first release step, whereas the slow diffusion of the hydrophobic drug through the lipid was responsible for the incomplete release obtained in the second phase. The polysaccharide chitosan was incorporated within the lipid matrix of the insulin-loaded cores, in order to provide potential mucoadhesive and absorption-enhancing properties to the system. In this case, after the dissolution of the pH-sensitive coating, the peptide was released in a controlled and progressive manner from lipid-chitosan cores,for both s/o/w and w/o/w methods of preparation. HPMC-AS microparticles containing lipid cores appear to constitute a promising approach for colon targeted drug delivery. They managed to control the drug release for a specific period of time, once the enteric coating had dissolved, thus potentially avoiding a premature release and enhancing delivery on the target site.