Gupta Piyush, Thilagavathi R, Chakraborti Asit K, Bansal Arvind K
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Punjab-160062, India.
Mol Pharm. 2005 Sep-Oct;2(5):384-91. doi: 10.1021/mp050004g.
Stabilization of an amorphous solid against devitrification can be achieved using additives that interact specifically with the parent molecule, and restrain it from rearranging into a crystal lattice. The amorphous form of celecoxib (CEL) was stabilized by poly(vinylpyrrolidone) (PVP), both in the solid state and during dissolution. A comprehensive characterization of CEL-PVP binary amorphous systems by thermal, spectroscopic, and computer simulation techniques provided greater insight into the molecular interaction between the two species. PVP antiplasticized the amorphous CEL, thus raising its glass transition temperature (T(g)) and restricting the molecular mobility. The T(g)()mix values for CEL-PVP binary amorphous systems of varying composition showed positive deviation from those predicted through the Gordon-Taylor/ Kelley-Bueche equation, thus indicating a molecular interaction between CEL and PVP. This was further substantiated by shifts observed in DSC melting endotherms of CEL, and FTIR bands for C=O stretching vibrations in PVP for CEL-PVP binary amorphous systems. Computer simulation showed stronger H-bonds between amido protons of CEL and carbonyl O of a monomeric unit of PVP, compared to those observed in pure amorphous CEL. These molecular interactions between CEL and PVP supported the stabilizing action of PVP for the amorphous form of CEL.
使用能与母体分子特异性相互作用并抑制其重排成晶格的添加剂，可以实现非晶态固体的抗析晶稳定化。塞来昔布（CEL）的非晶态形式在固态和溶解过程中都通过聚乙烯吡咯烷酮（PVP）实现了稳定化。通过热分析、光谱分析和计算机模拟技术对CEL-PVP二元非晶体系进行的全面表征，能更深入地了解这两种物质之间的分子相互作用。PVP使非晶态CEL发生反增塑，从而提高其玻璃化转变温度（T(g)）并限制分子流动性。不同组成的CEL-PVP二元非晶体系的T(g)()mix值与通过戈登-泰勒/凯利-比彻方程预测的值相比呈现正偏差，这表明CEL和PVP之间存在分子相互作用。CEL-PVP二元非晶体系中CEL的DSC熔融吸热峰和PVP中C=O伸缩振动的FTIR谱带出现的位移进一步证实了这一点。计算机模拟表明，与纯非晶态CEL中观察到的情况相比，CEL的酰胺质子与PVP单体单元的羰基O之间形成了更强的氢键。CEL和PVP之间的这些分子相互作用支持了PVP对CEL非晶态形式的稳定作用。
