Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Mol Pharm. 2020 Apr 6;17(4):1387-1396. doi: 10.1021/acs.molpharmaceut.0c00086. Epub 2020 Mar 24.
Punch-sticking during tablet compression is a common problem for many active pharmaceutical ingredients (APIs), which renders tablet formulation development challenging. Herein, we demonstrate that the punch-sticking propensity of a highly sticky API, celecoxib (CEL), can be effectively reduced by spherical crystallization enabled by a polymer assisted quasi-emulsion solvent diffusion (QESD) process. Among three commonly used pharmaceutical polymers, poly(vinylpyrrolidone) (PVP), hydroxypropyl cellulose (HPC), and hydroxypropyl methylcellulose (HPMC), HPMC was the most effective in stabilizing the transient emulsion during QESD and retarding the coalescence of emulsion droplets and the initiation of CEL crystallization. These observations may arise from stronger intermolecular interactions between HPMC and CEL, consistent with solution H NMR analyses. SEM and X-ray photoelectron spectroscopy confirmed the presence of a thin layer of HPMC on the surfaces of spherical particles. Thus, the sticking propensity was significantly reduced because the HPMC coating prevents direct contact between CEL and the punch tip during tablet compression.
压片过程中的黏冲是许多活性药物成分（APIs）的常见问题，这使得片剂配方的开发具有挑战性。在此，我们证明了通过聚合物辅助准乳液溶剂扩散（QESD）工艺实现的球形结晶，可以有效降低高粘性 API 塞来昔布（CEL）的黏冲倾向。在三种常用的药用聚合物中，聚维酮（PVP）、羟丙基纤维素（HPC）和羟丙基甲基纤维素（HPMC）中，HPMC 在 QESD 过程中最有效地稳定瞬时乳液，并延缓乳液液滴的聚结和 CEL 结晶的开始。这些观察结果可能源于 HPMC 和 CEL 之间更强的分子间相互作用，与溶液 H NMR 分析一致。SEM 和 X 射线光电子能谱证实了 HPMC 存在于球形颗粒的表面。因此，由于 HPMC 涂层在片剂压缩过程中防止了 CEL 与冲头尖端的直接接触，黏冲倾向显著降低。
