Drug Delivery Research Unit, School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
AAPS PharmSciTech. 2012 Dec;13(4):1255-65. doi: 10.1208/s12249-012-9850-z. Epub 2012 Sep 20.
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.
这项工作的目的是研究超临界二氧化碳（SC-CO₂）处理对孕酮（PGN）和 Gelucire 44/14 分散系统释放曲线的影响。采用部分因子设计法优化了气体饱和悬浮（PGSS）法的颗粒化工艺和制剂参数，并评价了三个独立响应的效果：PGSS 工艺产率、20 分钟后体外溶出度（E₂₀）和制备的 PGN 分散系统的 t₁/₂。实验域包括七个在两个水平下测量的因素，以确定哪些因素代表最大的变化量，从而对最终的 PGN 分散系统产生最大的影响。测试的变量包括超临界流体的温度（A）和压力（B）、样品装载量（C）、SC-CO₂ 处理时间（D）、超声处理（E）、药物与赋形剂的比例（F）和进入膨胀室的喷口直径（G）。方差分析表明，测试的因素对响应有显著影响（p 值<0.05）。结果发现，PGSS 工艺的最佳值为较高的压力（186 巴）、较高的温度（60°C）、较长的处理时间（30 分钟）和较低的 PGN 与赋形剂比例为 1:10。相应的加工产率为 94.7%，20 分钟后 PGN 的溶出度为 85.6%，t₁/₂为 17.7 分钟。结果表明，基于 Gelucire 44/14 的分散系统可能是递送 PGN 的一种有前途的制剂。通过析因设计实验可以优化 PGSS 法制备 PGN 载 Gelucire 44/14 分散系统。
