Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E, Minneapolis, MN 55455, United States.
Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E, Minneapolis, MN 55455, United States.
Int J Pharm. 2023 Jun 25;641:123041. doi: 10.1016/j.ijpharm.2023.123041. Epub 2023 May 16.
The development of a high quality tablet of Celecoxib (CEL) is challenged by poor dissolution, poor flowability, and high punch sticking propensity of CEL. In this work, we demonstrate a particle engineering approach, by loading a solution of CEL in an organic solvent into a mesoporous carrier to form a coprocessed composite, to enable the development of tablet formulations up to 40% (w/w) of CEL loading with excellent flowability and tabletability, negligible punch sticking propensity, and a 3-fold increase in in vitro dissolution compared to a standard formulation of crystalline CEL. CEL is amorphous in the drug-carrier composite and remained physically stable after 6 months under accelerated stability conditions when the CEL loading in the composite was ≤ 20% (w/w). However, crystallization of CEL to different extents from the composites was observed under the same stability condition when CEL loading was 30-50% (w/w). The success with CEL encourages broader exploration of this particle engineering approach in enabling direct compression tablet formulations for other challenging active pharmaceutical ingredients.
塞来昔布（CEL）片剂质量不佳，存在溶出度差、流动性差和冲头黏附倾向高的问题。在这项工作中，我们通过将 CEL 的有机溶剂溶液载入介孔载体中形成共处理复合材料，展示了一种颗粒工程方法，从而能够开发高达 40%（w/w）载药量的片剂配方，具有优异的流动性和可压性、可忽略的冲头黏附倾向，以及与晶型 CEL 的标准配方相比，体外溶出度提高了 3 倍。CEL 在药物载体复合材料中呈无定形态，在复合载药量≤20%（w/w）时，在加速稳定性条件下放置 6 个月后仍保持物理稳定性。然而，当 CEL 载药量为 30-50%（w/w）时，在相同的稳定性条件下，从复合材料中观察到 CEL 不同程度的结晶。CEL 的成功为其他具有挑战性的活性药物成分的直接压片配方提供了更广泛的探索这种颗粒工程方法的机会。
