PURPOSE: Piroxicam is a poorly soluble NSAID, whose solubility is enhanced when included into beta-cyclodextrin. The preparation of a piroxicam-beta-cyclodextrin inclusion compound using supercritical CO2 was investigated. METHODS: The solubility and the stability of piroxicam in supercritical CO2 were determined. Then, the influence of the temperature, the pressure and the time of exposure on the inclusion rate was studied. RESULTS: The solubility of piroxicam varied over a wide range depending on the temperature and pressure (from 0.006 to 1.500 mg/g of CO2). The temperature and the time of exposure had a great influence on the inclusion yield, while pressure did not and a complete inclusion was achieved by keeping a physical mixture of piroxicam and beta-cyclodextrin (1:2.5 mol/mol) for 6 hours at 150 degrees C and 15 MPa of CO2. This complex was characterized by Differential Scanning Calorimetry, differential solubility and Fourier Transform Infrared Spectrometry. CONCLUSIONS: Supercritical carbon dioxide may prove to be a novel useful complexation method of drugs into beta-cyclodextrin.
PURPOSE:Piroxicam is a poorly soluble NSAID, whose solubility is enhanced when included into beta-cyclodextrin. The preparation of a piroxicam-beta-cyclodextrin inclusion compound using supercritical CO2 was investigated. METHODS: The solubility and the stability of piroxicam in supercritical CO2 were determined. Then, the influence of the temperature, the pressure and the time of exposure on the inclusion rate was studied. RESULTS: The solubility of piroxicam varied over a wide range depending on the temperature and pressure (from 0.006 to 1.500 mg/g of CO2). The temperature and the time of exposure had a great influence on the inclusion yield, while pressure did not and a complete inclusion was achieved by keeping a physical mixture of piroxicam and beta-cyclodextrin (1:2.5 mol/mol) for 6 hours at 150 degrees C and 15 MPa of CO2. This complex was characterized by Differential Scanning Calorimetry, differential solubility and Fourier Transform Infrared Spectrometry. CONCLUSIONS: Supercritical carbon dioxide may prove to be a novel useful complexation method of drugs into beta-cyclodextrin.
Authors: Tarja Toropainen; Teemu Heikkilä; Jukka Leppänen; Laura Matilainen; Sitaram Velaga; Pekka Jarho; Johan Carlfors; Vesa-Pekka Lehto; Tomi Järvinen; Kristiina Järvinen Journal: Pharm Res Date: 2007-03-24 Impact factor: 4.580