RELEASE OF DRUGS FROM ETHYL CELLULOSE MICROCAPSULES (DIFFUSION PELLETS) WITH PORE FORMERS AND PORE FUSION

By adding hydroxypropyl methyl cellulose (HPMC) to aqueous ethyl cellulose (EC) dispersions with 20% dibutyl sebacate (DBS) as plasticizer, it is possible to manufacture diffusion pellets (coated pellets) which contain water-filled pores in the release-controlling membrane after extraction of the HPMC at the beginning of the release process. In the case of 25% HPMC and an acidic medium, these pores do, however, close irreversibly within 2 h as the result of subsequent fusion if release takes place above the minimum film-forming temperature. Thereafter, the release rate is just as slow as it is without the HPMC additive. Thus, the drug is released practically exclusively via the distribution-diffusion mechanism. Pores also close in the case of an HPMC content of 30-40% but not completely. In alkaline release media, the number of pores formed does not decrease with time, due to ionized carboxylic groups of EC. This is, however, of secondary importance for the in vivo performance as it is shown to be expected that the pores of the coated pellets will close irreversibly during previous passage through acidic pH (e.g. the stomach).