A one-pot method to enhance dissolution rate of low solubility drug molecules using dispersion polymerization in supercritical carbon dioxide.
The surfactant assisted polymerization of 1-vinyl-2-pyrrolidone in supercritical carbon dioxide in the presence of Piroxicam, selected as a model of a low aqueous solubility drug, was studied in order to prepare in a single step a polymeric composite to enhance the rate of dissolution of the pharmaceutical compound. Reactive entrapping was carried out at 65 degrees C in the P range 21-38MPa. Under proper operative conditions we obtained the composite under the form of sub-micron spherical particles with relatively narrow particle size distribution. Drug loadings higher than 12% (w/w) were obtained and XRD and Raman spectroscopy suggest that the anti-inflammatory agent is dispersed in the matrix with a non-crystalline structure. The dissolution rate of the drug from the composites was significantly faster both than that of the pure compound and of its physical mixture with the polymer. Collected results suggest that the proposed one-pot process can be used to prepare polymer based composites to increase bioavailability of low solubility drugs without utilization of toxic solvents and under mild temperature conditions.
Galia
Alessandro
A
Dipartimento di Ingegneria Chimica dei Processi e dei Materiali, Unversità di Palermo, Viale delle Scienze Ed 6, 90128 Palermo, Italy. galia@dicpm.unipa.it
Scialdone
Onofrio
O
Filardo
Giuseppe
G
Spanò
Tiziana
T
D002245:Carbon Dioxide / Q000737:chemistry*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D010316:Particle Size; D010894:Piroxicam / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis*; D011760:Pyrrolidinones; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D004337:Drug Carriers; D011108:Polymers; D011760:Pyrrolidinones; D010894:Piroxicam; D002245:Carbon Dioxide; C028537:2-pyrrolidone