SCCO_2-ASSISTED PREPARATION OF OMEPRAZOLE/CYCLODEXTRIN INCLUSION COMPLEXES. COMPARATIVE STUDY WITH CONVENTIONAL METHODS

摘要

Supercritical carbon dioxide is a very attractive medium for pharmaceutical processing as an alternative to aqueous and organic solvents. Many drug formulations use cyclodextrins since their lipophilic cavities provide microenvironments where drug molecules can enter and form inclusion complexes, leading to an increase in the solubility and stability of the drug. Omeprazole shows low stability and poor solubility in water. The aim of this study was to test the viability of preparing omeprazole/cyclodextrins inclusion complexes using dense carbon dioxide in order to enhance these parameters. The CO_2-assisted method was compared with kneading (KN), a conventional inclusion complex formation method. In addition, data were compared with the physical mixture, omeprazole with lactose instead cyclodextrin, and pure omeprazole. As omeprazole is a very sensitive drug and because in our first experiments in scCO_2 at 40°C, we observed omeprazole degradation, we decided to test the viability of performing the inclusion complexes at low temperature, near the critical temperature of CO_2 (scCO_2) and also at room temperature using liquid CO_2 (LIQ CO_2). All powders obtained were kept at dark conditions and were analysed by DSC, FTIR and dissolution studies in order to compare the processing methods.