Title: Utilization of supercritical carbon dioxide for development of advanced pharmaceutical formulations with valsartan and carvedilol

Abstract

Supercritical carbon dioxide (scCO2) is a green medium that allows production of solvent-free formulations without the use of excipients and organic solvents. In this study, it was used for processing of valsartan and carvedilol in order to produce formulations that will increase bioavailability of drugs. Both valsartan and carvedilol are cardiovascular drugs that have low bioavailability (around 20-30%). In addition, biodegradable and biocompatible pharmaceutical polymers (Soluplus®, hydroxypropyl methylcellulose acetate succinate, and Eudragit® E100) were tested as carriers of valsartan and carvedilol. It was shown that proposed one-step process performed at 30 MPa during 2 h allowed for plasticization of all tested polymers. All characterization tests (SEM, FTIR, DSC, XRD) indicated that drugs were dispersed in polymeric carriers, whereby amorphous solid dispersions with density in the range from 327 to 667 kg/m3 and porosity from 12 to 78 vol% were obtained. Controlled release of drugs was influenced by solubility of polymers in the tested release medium that simulate body fluids (HCl and PBS). Dissolution of valsartan and carvedilol from formulations was increased compared to untreated drugs. Proposed process enabled preparation of two-component system that has advanced properties compared to pristine components as well as commercial formulations. The obtained results provide framework for future development of environmental friendly method for production of drug delivery systems.