Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions

Abstract

Formulation of solid dispersions is one of the most feasible strategies for overcoming the poor drugs’ solubility – one of the major issues affecting drug bioavailability and therapeutic outcomes. Since traditional methods used for preparation of solid dispersions often require usage of organic solvents, it is of great importance to seek for more environment-friendly methods. It has been demonstrated that supercritical (sc) CO2 may be effectively utilized for dispersion of drugs into the suitable carrier (polymer), thus obtaining solid dispersions with the improved drug dissolution rate. The aim of the presented study was to investigate the potential of scCO2 for preparation of poorly soluble antihypertensive drugs (carvedilol and valsartan) solid dispersions in the conventional pharmaceutical polymers (polyvinilypyrolidone-PVP and hypromellose-HPMC). Prepared solid dispersions were characterized by scanning electron microscopy, differential scanning calorimetry and Fourier-transform infrared spectroscopy; their porosity and density were determined and drug dissolution rate was assessed and compared to the results obtained from solid dispersions prepared by the traditional solvent casting method. Selected samples were tested for their tableting properties as well. It has been demonstrated that scCO2 may be successfully applied for preparation of carvedilol or valsartan solid dispersions with the improved drug dissolution rate. Further characterization revealed the nature of interactions between the drugs and selected polymers. Due to the low density (and high porosity), some of the prepared solid dispersions may be used for further development of the floating dosage forms. It has also been demonstrated that some of the prepared dispersions have excellent compressibility and compactibility, which is of great importance for further development of solid dosage forms. The obtained results provide framework for further development of environment-friendly methods in pharmaceutical development and production