(569i) Supercritical Impregnation of Anticancer Drug into Biodegradable Polymer
AIChE Annual Meeting
2008
2008 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Pharmaceuticals Poster Session
Wednesday, November 19, 2008 - 6:00pm to 8:30pm
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.
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2008 Annual Meeting
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