PREPARATION AND EVALUATION OF DRUG/? - CYCLODEXTRIN SOLID INCLUSION COMPLEXES BY SUPERCRITICAL FLUID TECHNOLOGY

摘要

Modern drugs are often lipophilic compounds. To act on the target structures, the drugs must be dissolved in physiological fluids and absorbed through entrance ports. Due to costs, convenience and compliance, oral application of solid forms is the preferential way. Since the bioavailability of orally applied drugs depends on the velocity of dissolution rate and absorption, methods to improve the dissolution are required. The complexation of drugs with cyclodextrins is known to improve the solubility, permeability and bioavailability. In this study, a Controlled Particle Deposition (CPD) method has been developed for the preparation of inclusion complexes (β-cyclodextrin) with non-polar drugs (ibuprofen) using supercritical carbon dioxide (scCO_2) as an alternative to solvents. The complexes were prepared in an incubation vessel with separate chambers for the drug and the complexing agent. The resulting product was compared to complexes obtained by freeze-drying or coprecipitation. Differential scanning calorimetric (DSC) showed almost complete inclusion of ibuprofen in the scCO_2-product and in the freeze-dried product but significant amounts of not complexed ibuprofen in the coprecipitated material. HPLC-analysis of the ibuprofen content in the complexes confirmed the almost complete inclusion of ibuprofen in β-cyclodextrin in the scCO_2- and freeze-dried complex. In contrast, the coprecipitated complex appeared like a physical mixture with about 35% of the total ibuprofen content outside the β-cyclodextrin. The inclusion rates obtained, however, were about 1:11 (mol) in the scCO_2-complex but about 1:1 in the freeze-dried complex. Taking together, the method developed for Controlled Particle Deposition is very useful for the production of highly pure β-cyclodextrin complexes, avoiding partitions of uncomplexed material. The efficacy of the process must still be improved.