Regenerated cellulose capsules for controlled drug delivery: Part IV. In-vitro evaluation of novel self-pore forming regenerated cellulose capsules

Abstract

In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC capsules were fabricated using a modified dip-coating approach, which yielded an assembled dosage form that was equivalent in size and shape to a conventional gelatin two-piece hard shell capsule. Drug release characteristics from RC capsules were evaluated using potassium chloride, diphenhydramine hydrochloride, tramadol hydrochloride, niacinamide, acetaminophen and ketoprofen as model APIs. The RC capsules act as a barrier coated reservoir device that releases the enclosed API at a zero order release rate. When comparing all the API's release behavior from RC capsules, a power-law relationship was observed between their zero-order release rates and their respective aqueous solubilities. Osmotic as well as diffusive mechanisms are involved in the release of the enclosed API. The osmotic mechanism's contribution to zero order release rate increases as the aqueous solubility of the tested APIs inside the capsule increases. The osmotic mediated flux and the apparent diffusivity of the APIs through the capsule wall is a competitive process and the osmotic mediated flux of the enclosed API begins to override its diffusivity through the capsule wall as the API solubility increases. This behavior is attributed to the wide range of pore sizes observed in RC membranes, from our prior analysis. The fluid permeability analysis shows that the RC capsules presented in this work may be better suited for osmotic drug delivery applications than conventional encapsulated systems described in the literature.