The Effects of Supercritical Carbon Dioxide Processing on Progesterone Dispersion Systems: a Multivariate Study

Abstract

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.

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

“…231 Biphasic dissolution of the formulation indicated a significantly higher concentration of the drug in the aqueous (0.1 mol/L HCl) as well as organic (octanol) layer relative to the physical mixture. In another study, progesterone solid dispersions were prepared with PGSS 232 . Amongst the tested variables, a yield of 94.7% and the highest extent of progesterone dissolution after 20 min (85.6%) was observed for lower progesterone-to-excipient ratio (1:10) and process values of higher pressure (186 bar), higher temperature (60 °C), and a longer processing time (30 min).…”

Supercritical CO2 for the Reactive Precipitation of Calcium Carbonate: Uses and Applications to Industrial Processing

“…Casettari et al report the use of PASS for the development of mucoadhesive particles form chitosan and poly-lactic acid for gastrointestinal drug delivery [24]. Falconer et al present a multivariate study on the effect of different operating conditions for the preparation of progesterone loaded gelucire particles and the results demonstrate that not only the independent variables of pressure and temperature influence the result but also the interaction between them influence the yield of the process [25]. Other examples, such as the encapsulation of caffeine or trans-chalcone in lipid carriers have been presented by Sousa et al [36,27].…”