title: Comparison of solid dispersions produced by supercritical antisolvent and spray-freezing technologies.
abstract: Oxeglitazar is a new orally administered poorly water soluble active substance used in the treatment of type II diabetes. The objective of this work was to improve its dissolution kinetics using supercritical antisolvent (SAS) and spray-freezing (SF) techniques. Oxeglitazar was formulated with various excipients, including: Poloxamer 188 and 407, polyethylene glycol (PEG) 8000 and polyvinylpyrrolidone (PVP) K17 in a 1:1 weight ratio. In the SAS technology, pharmaceutical ingredients were dissolved in an appropriate solvent, and the feed solution was dispersed through a capillary nozzle in supercritical CO(2) (SC CO(2)). Dichloromethane (DCM), chloroform (CHCl(3)), and a binary co-solvent system of chloroform-ethanol (EtOH/CHCl(3) 50:50, v/v%) were tested. In the SF process, tert-butanol (tBuOH) was used as solvent. The feed solution was injected into liquid nitrogen through a capillary nozzle located above the surface of the boiling nitrogen. Frozen particles were collected and freeze-dried for 30 h. Formulations were compared in terms of particle morphology, particle size, flow properties, crystallinity, polymorphic purity, residual solvent content, precipitation yield, drug content, specific surface area and dissolution kinetics. SAS and SF processed formulations exhibited enhanced dissolution rates. Within 5 min, the amount of dissolved drug varied from 31.6 to 64.3% for SAS and from 77.9 to 96.9% for freeze-dried formulations while only 30.5% was dissolved from raw drug. Apart from oxeglitazar/PVP K17, SAS prepared solid dispersions were characterized by high crystallinity and acicular shape. Freeze-dried formulations consisted of porous spherical particles with high amorphous content (94.2-100%).
authors.affiliation: UMR 6181 CNRS - M2P2 (Modélisation, Mécanique et Procédés Propres), Université Paul Cézanne Aix-Marseille, Europôle de l'Arbois, RD 543, 13545 Aix-en-Provence Cedex 04, France. Elisabeth.badens@univ-cezanne.fr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Badens
authors.forename: Viktor
authors.initials: V
authors.lastname: Majerik
authors.forename: Géza
authors.initials: G
authors.lastname: Horváth
authors.forename: László
authors.initials: L
authors.lastname: Szokonya
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bosc
authors.forename: Eric
authors.initials: E
authors.lastname: Teillaud
authors.forename: Gérard
authors.initials: G
authors.lastname: Charbit
mesh_terms: D001584:Benzoxepins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005612:Freeze Drying / Q000379:methods*; D005615:Freezing; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001584:Benzoxepins; D012997:Solvents; C525605:oxeglitazar