In vitro evaluation of water-insoluble silicates and polyvinylpyrrolidone-vinyl acetate as oral carriers for amorphous ritonavir. dissolution enhancement and the role of phosphatidylcholine

Abstract

Porous silicates have been investigated as drug carriers to promote the solubility and in vitro dissolution of poorly water-soluble drugs, owing to their potential to adsorb drug molecules in the amorphous form within their structural cavities. This study aimed to evaluate the efficiency of bentonite (BT), Aeroperl 300 Pharma (AP), and Florite PS-200 (FR) as water-insoluble silicate drug carriers, and the polymer polyvinylpyrrolidone-vinyl acetate (PVPVA) in improving the dissolution of ritonavir (RTV). The effect of phosphatidylcholine (PC) as a water-insoluble excipient on drug dissolution was also investigated. Multiple linear regression analysis of the dissolution data was performed to identify the factors influencing dissolution, complemented by mechanistic simulations of the best-performing carrier. The in vitro dissolution rank order of carriers with a 30% drug load (DL) based on % dissolved 300min was AP = FR > PVPVA = BT in the absence of PC, and AP > FR > PVPVA > BT with PC. The extent of dissolution for all formulations increased in the presence of PC, with the AP and FR formulations exceeding that of marketed formulations. High drug load did not significantly affect the dissolution profile of silicate formulations, but it reduced dissolution from PVPVA solid dispersion. In silico results showed that silicate pore size governed RTV release, with open pores forming fewer hydrogen bonds, allowing more facile RTV release. The significant improvement in RTV dissolution with AP and FR supports the use of these carriers for poorly soluble drugs as alternatives to traditional polymers, especially for formulations with high drug loads.