Impregnation of paclitaxel into poly(dl-lactic acid) using high pressure mixture of ethanol and carbon dioxide

Abstract

Paclitaxel (PT) is a mitotic inhibitor used in cancer chemotherapy. Impregnation of PT into amorphous poly(DL-lactic acid) (PDLLA) in mixtures of high-pressure ethanol (EtOH) and carbon dioxide (CO2) at various compositions was investigated at 313 K and 20 MPa. It was demonstrated that the high pressure EtOH–CO2 mixture is a promising solvent for fabrication of polymer-based drug delivery systems (DDS) materials, which enables the avoidance of drug deterioration due to processing at elevated temperatures. A mixture with 25 mol% EtOH allowed impregnation of the largest amount of PT in the PDLLA matrix. The amount of impregnated PT in the EtOH–CO2 mixtures was 10 times and 28 times larger than those in supercritical CO2 and liquid EtOH, respectively. The composition of the EtOH–CO2 mixture affected the amount of PT that could be impregnated. The increase in the amount of impregnated PT in the mixture is probably attributed to plasticization of PDLLA and increased solubility of PT into the EtOH–CO2 mixture. The degree of swelling observed in the PDLLA caused by plasticization depended on the composition of the EtOH–CO2 mixture, with the volume increasing to 1.7 times the initial size for a mixture containing 40 mol% EtOH at 313 K and 20 MPa. Physical aging was induced after the swollen PDLLA in supercritical CO2 was vitrified by pressure drop from 20 MPa to atmospheric pressure at 313 K, whereas vitrification hardly occurred in the EtOH–CO2 mixture under the same conditions.