(569i) Supercritical Impregnation of Anticancer Drug into Biodegradable Polymer

Impregnation of anticancer drug into Poly (lactic acid) (PLA) via supercritical carbon dioxide (scCO2) has been investigated. Controlled release drug delivery system (DDS) material is a promising application of PLA, due to its biodegradability, biocompatibility and bioresorbability. Impregnation of drug with scCO2 is beneficial because of non-toxicity, plasticization effect on PLA, and low operating temperature without deterioration of drugs. In this work, we demonstrated impregnation of paclitaxel (PT), a typical anticancer drug, into amorphous PLA for biodegradable DDS system. Ethanol (EtOH) was used as co-solvent to enlarge the solubility of PT.

Prior to the material processing, solubility of PT into both scCO2 and a EtOH-scCO2 mixture was evaluated. Solubility measurement system for small amount of sample into the co-solvent-scCO2 mixture was developed for expensive drugs. PT solubility to scCO2 was 1.2– 2.1 x 10-6 mol/ mol at 313 K, under 10 – 37.5 MPa. The solubility was drastically increased in the EtOH-scCO2 mixture. PT solubility to the 5 mol % EtOH-scCO2 mixture was 1.4 – 1.9 x 10-5 mol/ mol at 313 K under 10 – 15 MPa.

Impregnation of PT into amorphous PLA was investigated at 313 K, under 20 MPa with a variety of EtOH-scCO2 mixtures (0 to 75 mol % EtOH). We confirmed that amount of impregnated PT was increasing by the addition of EtOH. The amount of impregnated PT in pure scCO2 was 0.1 micro g/ mg (impregnated PT/ PLA), whereas that in EtOH-scCO2 mixtures were 4 to 10-times larger than that in pure scCO2 (0.4 – 1.1 micro g/ mg). It is noteworthy that the sample impregnated at 25 mol % EtOH-scCO2 mixture shows the maximum amount of PT. It is expected that an increase of EtOH concentration would increase the PT solubility but that EtOH would suppress plasticization because of a poor solvent for PLA. Therefore, the maximum at 25 mol % EtOH appears probably due to competition of these effects. Swelling phenomenon of the PLA in the EtOH-scCO2 mixture will be also discussed in the conference.