2軸エクストルーダによるプランルカスト水和物の固体分散体の調製と添加液体の与える影響―HPMCを担体として用いた場合―

抄録

The solid dispersion method, by which a drug is amorphously dispersed in a carrier, is one of the pharmaceutical approaches most commonly employed to increase the bioavailability of poorly water soluble drugs. In the extruding method performed by various operations that combine heating, pressurization, kneading and extruding at the same time, solid dispersion can be generated continuously and in large quantities.

In this study, we prepared a solid dispersion of Pranlukast hydrate (ONON) as a model drug using Hydroxypropylmethylcellulose (HPMC) as a carrier using a twin screw extruder. At that time, we investigated the nature of the solid dispersion obtained by examining crystallinity, solubility and interaction between drug and carrier under changes in the extrusion conditions, operation temperature and the kind and quantity of additive liquid. Additionally, solid dispersion was compared with physical mixture.

As a result, we could not only improve the solubility but also facilitate handling the machine by adding an appropriate concentration of Tween 80 solution. Moreover, the drug crystallinity disappeared in solid dispersion produced under all extrusion conditions, regardless of temperature. But the extrusion pressure increased as the operation temperature decreased, and the solubility of solid dispersion produced under lower temperatures was better than that produced under higher temperatures.

Based on the findings described above, we could improve the dissolution property of this drug remarkably by selecting an appropriate extrusion temperature as well as the kind and concentration of additive liquid.