Erodible Coatings Based on HPMC and Cellulase for Oral Time-Controlled Release of Drugs

Oral drug delivery systems for time-controlled release, intended for chronotherapy or colon targeting, are often in the form of coated dosage forms provided with swellable/soluble hydrophilic polymer coatings. The latter are responsible for programmable lag phases prior to release, due to their progressive hydration in the biological fluids. When based on high-viscosity polymers and/or manufactured by press-coating, the performance of functional hydroxypropyl methylcellulose (HPMC) layers was not fully satisfactory. Particularly, it encompassed an initial phase of slow release because of outward diffusion of the drug through a persistent gel barrier surrounding the core. To promote erosion of such a barrier, the use of a cellulolytic product (Sternzym® C13030) was here explored.

For this purpose, the dry mass loss behavior of tableted matrices based on various HPMC grades, containing increasing percentages of Sternzym® C13030, was preliminarily studied, highlighting a clear and concentration-dependent effect of the enzyme especially with high-viscosity polymers. Subsequently, Sternzym® C13030-containing systems, wherein the cellulolytic product was either incorporated into a high-viscosity HPMC coating or formed a separate underlying layer, were manufactured. Evaluated for release, such systems gave rise to more reproducible profiles, with shortened lag phases and reduced diffusional release, as compared to the reference formulation devoid of enzyme. More on erodible coatings

Keywords: Swellable/erodible delivery systems, pulsatile release, hydroxypropyl methylcellulose, press-coating, cellulase, enzymatic degradation, colloidal silica, ethylcellulose, Ethocel®, hydroxypropyl methylcellulose 2910, Methocel® E50LV, Methocel® K100LV, Methocel® K4M, Methocel® K15M, Methocel® K100M, maltodextrin, Glucidex® IT19W, microcrystalline cellulose, Vivapur®101, sodium starch glycolate, Explotab®