Supercritical antisolvent versus coevaporation: preparation and characterization of solid dispersions.
The objective of this work was to improve the dissolution rate and aqueous solubility of oxeglitazar. Solid dispersions of oxeglitazar in PVP K17 (polyvinilpyrrolidone) and poloxamer 407 (polyoxyethylene-polyoxypropylene block copolymer) were prepared by supercritical antisolvent (SAS) and coevaporation (CoE) methods. Drug-carrier formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography, UV/VIS spectroscopy and in vitro dissolution tests. The highest dissolution rate (nearly 3-fold higher than raw drug) was achieved by preparation of drug/PVP K17 coevaporate. Oxeglitazar/PVP K17 solid dispersions were stabilized by hydrogen bonding but contained higher amount of residual dichloromethane (DCM) than poloxamer 407 formulations regardless of the method of preparation. SAS prepared oxeglitazar/poloxamer 407 dissolved more than two times faster than raw drug. However, unlike PVP K17, poloxamer 407 did not form a single phase amorphous solid solution with oxeglitazar which has been manifested in higher degrees of crystallinity, too. Among the two techniques, evaluated in this work, conventional coevaporation resulted in higher amorphous content but SAS reduced residual solvent content more efficiently.
Majerik
Viktor
V
Department of Chemical Engineering Science, University of Pannonia, Veszprém, Hungary. majerikv@almos.vein.hu
Horváth
Géza
G
Szokonya
László
L
Charbit
Gérard
G
Badens
Elisabeth
E
Bosc
Nathalie
N
Teillaud
Eric
E
D001584:Benzoxepins / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002849:Chromatography, Gas; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006860:Hydrogen Bonding; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008752:Methylene Chloride / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D001584:Benzoxepins; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D012997:Solvents; D020442:Poloxamer; D008752:Methylene Chloride; D011205:Povidone; C525605:oxeglitazar