Release Mechanisms of a Sparingly Water-Soluble Drug from Controlled Porosity-Osmotic Pump Pellets Using Sulfobutylether-β-Cyclodextrin as Both a Solubilizing and Osmotic Agent

The purpose of this work is to delineate the release mechanisms of a sparingly water-soluble drug, prednisolone (PDL), from a microporous or controlled porosity-osmotic pump pellet (CP-OPP) using sulfobutylether-beta-cyclodextrin (CD) as both a solubilizing and osmotic agent. All factors, osmotic and diffusional, influencing drug release as described by the Theeuwes and Zentner equation were partially demonstrated in an earlier paper(1) and are further quantitatively evaluated here to determine whether the equation may be applied to CP-OPPs. The PDL release rate from the CP-OPPs containing precomplexed PDL follows the zero-order kinetics for up to 30-40% of drug release during the first 1-2 h and subsequently nonzero order kinetics. The zero-order drug release phase reveals the main contribution is from osmotic pumping with a negligible diffusion component, resulting from the nearly constant driving forces in the system. The nonzero order drug release phase is associated with the dynamic changes in the system (e.g., declining osmotic driving force and greater diffusion component with time). In addition, the parameters related to membrane characteristics were determined, and the effect of viscosity was evaluated for the pellet system. The membranes coated on the CP-OPPs are less permeable to water or solutes than the membranes coated on the previously reported tablets. The viscosity due to the CD decreases as a function of CD concentration, which partly affects the observed drug release profiles. The viscosity effect of CD is significant and captured in a hydraulic permeability term. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1992-2000, 2009