Division of Pharmaceutics, The University of Texas at Austin, 1 University Station A1920, Austin, Texas 78712, USA.
J Pharm Sci. 2010 Mar;99(3):1239-53. doi: 10.1002/jps.21893.
KinetiSol Dispersing (KSD) is a novel high energy manufacturing process investigated here for the production of pharmaceutical solid dispersions. Solid dispersions of itraconazole (ITZ) and hypromellose were produced by KSD and compared to identical formulations produced by hot melt extrusion (HME). Materials were characterized for solid state properties by modulated differential scanning calorimetry and X-ray diffraction. Dissolution behavior was studied under supersaturated conditions. Oral bioavailability was determined using a Sprague-Dawley rat model. Results showed that KSD was able to produce amorphous solid dispersions in under 15 s while production by HME required over 300 s. Dispersions produced by KSD exhibited single phase solid state behavior indicated by a single glass transition temperature (T(g)) whereas compositions produced by HME exhibited two T(g)s. Increased dissolution rates for compositions manufactured by KSD were also observed compared to HME processed material. Near complete supersaturation was observed for solid dispersions produced by either manufacturing processes. Oral bioavailability from both processes showed enhanced AUC compared to crystalline ITZ. Based on the results presented from this study, KSD was shown to be a viable manufacturing process for the production of pharmaceutical solid dispersions, providing benefits over conventional techniques including: enhanced mixing for improved homogeneity and reduced processing times.
KinetiSol 分散（KSD）是一种新型的高能制造工艺，用于生产药物固体分散体。通过 KSD 生产伊曲康唑（ITZ）和羟丙甲纤维素的固体分散体，并与通过热熔挤出（HME）生产的相同配方进行比较。通过调制差示扫描量热法和 X 射线衍射对材料的固态特性进行了表征。在过饱和条件下研究了溶解行为。使用 Sprague-Dawley 大鼠模型确定了口服生物利用度。结果表明，KSD 能够在 15 秒内生产无定形固体分散体，而 HME 生产需要超过 300 秒。通过 KSD 生产的分散体表现出单相固态行为，表明只有一个玻璃化转变温度（Tg），而通过 HME 生产的组合物则表现出两个 Tg。与 HME 加工材料相比，通过 KSD 生产的组合物的溶解速率也有所提高。通过这两种制造工艺生产的固体分散体都观察到几乎完全过饱和。两种工艺的 AUC 均显示出与结晶 ITZ 相比，生物利用度得到提高。根据本研究的结果，KSD 被证明是生产药物固体分散体的可行制造工艺，与传统技术相比具有以下优势：增强混合以提高均一性和缩短加工时间。
