超臨界状態の CO が薬物-ポリマー系の特性、溶解性、ビカルタミド含有錠の特性にどのような影響を与えるか？

How Does the CO in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

• Agata Antosik-Rogóż
• Joanna Szafraniec-Szczęsny
• Krzysztof Chmiel
• Justyna Knapik-Kowalczuk
• Mateusz Kurek
• Karolina Gawlak
• Vittorio P Danesi
• Marian Paluch
• Renata Jachowicz

抄録

新規製剤への需要の高まりに伴い、粒子径を小さくし、包接錯体や固体分散体の形成を可能にする方法として、超臨界流体技術、特にCOが製薬技術に導入されるようになってきた。本論文では、可溶性の低い抗アンドロゲン薬ビカルタミドと高分子賦形剤（Ｍａｃｒｏｇｒｏｇｏｌ６０００またはＰｏｌｏｘａｍｅｒ４０７のいずれか）を含む二元系の調製におけるｓｃＣＯの応用について述べる。粒子径および形態の変化を、走査型電子顕微鏡およびレーザー回折測定を用いて追跡した。熱的特性を評価するために示差走査熱量測定を適用し、一方、系の結晶構造の変化を決定するために粉末Ｘ線回折法を用いた。また、ビカルタミドの溶解も考慮した。二価固体分散体をさらに圧縮し、錠剤の属性を評価した。錠剤は、製造後および気候室での保存後に直接分析した。得られた結果は、超臨界COの使用が粒子の形態学的変化と薬物溶解の改善をもたらしたことを示している。処理した二元系を含むブレンドの流動性は悪かったが，錠剤への圧縮に成功し，薬物放出性が向上した。

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.