title: The effects of supercritical carbon dioxide processing on progesterone dispersion systems: a multivariate study.
abstract: The aim of this work was to investigate the effects of supercritical carbon dioxide (SC-CO(2)) processing on the release profiles of progesterone (PGN) and Gelucire 44/14 dispersion systems. A fractional factorial design was conducted for optimization of the particles from gas-saturated suspension (PGSS) method and formulation parameters and evaluating the effects of three independent responses: PGSS process yield, in vitro dissolution extent after 20 min (E(20)) and t (1/2) for prepared PGN dispersion systems. The experimental domain included seven factors measured at two levels to determine which factors represent the greatest amount of variation, hence the most influence on the resulting PGN dispersion systems. Variables tested were temperature (A) and pressure (B) of the supercritical fluid, sample loading (C), SC-CO(2) processing time (D), sonication (E), drug-to-excipient ratio (F) and orifice diameter into the expansion chamber (G). The analysis of variance showed that the factors tested had significant effects on the responses (p value <0.05). It was found that the optimum values of the PGSS process are higher pressure (186 bar), higher temperature (60°C), a longer processing time (30 min) and lower PGN-to-excipient ratio of 1:10. The corresponding processing yield was 94.7%, extent of PGN dissolution after 20 min was 85.6% and the t (1/2) was 17.7 min. The results suggest that Gelucire 44/14-based dispersion systems might represent a promising formulation for delivery of PGN. The preparation of PGN-loaded Gelucire 44/14 dispersion systems from a PGSS method can be optimized by factorial design experimentation.
authors.affiliation: Drug Delivery Research Unit, School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. j.falconer@auckland.ac.nz
authors.forename: James R
authors.initials: JR
authors.lastname: Falconer
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wen
authors.forename: Sara
authors.initials: S
authors.lastname: Zargar-Shoshtari
authors.forename: John J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Farid
authors.initials: F
authors.lastname: Mohammed
authors.forename: Judy
authors.initials: J
authors.lastname: Chan
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D011374:Progesterone / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
chemical_list: D005079:Excipients; C104509:gelucire 44-14; D002245:Carbon Dioxide; D011092:Polyethylene Glycols; D011374:Progesterone