Enhancement of Valsartan Dissolution Rate by the Increased Porosity of Pellets Using Supercritical CO2: Optimization via Central Composite Design

Purpose The aim of this research was to optimize the enhancement the porosity of pellet containing valsartan (VAL) using carbon dioxide at supercritical pressure (scCO(2)) via central composite design (CCD) to increase the release at simulated gastrointestinal fluids (pH 1.2 and 6.8). Methods To prepare the pellet, an extrusion/spheronization apparatus was used. Central composite design was applied to reach the optimum % porosity, dissolution efficiency (DE %) for both different pH. The size, shape, mechanical properties, porosity, specific surface area, pore size, pre-, and post-scCO(2) pellets were analyzed for surface shape as well as in vitro drug release behavior was investigated. Results The maximum % porosity (42.89%), DE % at pH 1.2 (36.08%), and at pH 6.8 (99.68%) were observed when 50 degrees C, 200 bar, 72 min, and 27 min were the temperature, pressure, soaking time, and depressurize time, respectively. Pre- and post-scCO(2) pellet release rates were much greater at pH 1.2 than the VAL powder form, with around 30 to 50% of the release occurring at 6 h, sequential. At pH 6.8, post-scCO(2) pellets release almost 100% of the drug in 30 min, while the VAL powder and pre-scCO(2) pellets release approximately 72% and 92% of the drug during 6 h, respectively. Conclusion Thus, the dissolving rate of the poorly water-soluble VAL was improved by using a post-scCO(2) pellet in pH 1.2 and pH 6.8 environments by an increase in the porosity of the pellet due to the scCO(2) treatment.