Reduction of Punch-Sticking Propensity of Celecoxib by Spherical Crystallization via Polymer Assisted Quasi-Emulsion Solvent Diffusion
Reduction of Punch-Sticking Propensity of Celecoxib by Spherical Crystallization via Polymer Assisted Quasi-Emulsion Solvent Diffusion
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DOI：
10.1021/acs.molpharmaceut.0c00086
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发表时间：
2020-04-06
影响因子：
4.9
通讯作者：
Sun, Changquan Calvin
中科院分区：
文献类型：
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作者：
Chen, Hongbo;Paul, Shubhajit;Sun, Changquan Calvin
片剂压缩过程中的冲片粘附是许多活性药物成分（API）的常见问题，这使得片剂制剂开发具有挑战性。在此，我们证明了高粘性API塞来昔布（CEL）的穿孔粘附倾向可以通过聚合物辅助的准乳液溶剂扩散（QESD）工艺实现的球形结晶来有效降低。在三种常用的药物聚合物聚乙烯吡咯烷酮（PVP）、羟丙基纤维素（HPC）和羟丙基甲基纤维素（HPMC）中，HPMC在QESD期间稳定瞬时乳液和延迟乳液液滴聚结和CEL结晶引发方面最有效。这些观察结果可能来自HPMC和CEL之间更强的分子间相互作用，与溶液H-1 NMR分析一致。SEM和X-射线光电子能谱证实了在球形颗粒表面上存在一薄层HPMC。因此，粘附倾向显著降低，因为HPMC包衣可防止片剂压片期间CEL与冲头尖端直接接触。
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-1 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.