文献类型：期刊文献

英文题名：Resurrecting the 'Disappearing Polymorph' of Rotigotine via Conformational Landscape Engineering

作者：Yi, Dongxu[1]; Qi, Minghui[2,5]; Xu, Shaohong[1]; Qi, Yonghua[1]; Xia, Ran[1]; Wu, Hao[3,4]; Ren, Guobin[2,6]

机构：[1] School of Pharmacy, Xinxiang University, Henan, Xinxiang, 453003, China; [2] School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China; [3] Children's Hospital Affiliated to Zhengzhou University, Henan, Zhengzhou, 450018, China; [4] Henan Children’ s Hospital Zhengzhou Children’s Hospital, Henan, Zhengzhou, China; [5] Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Laboratory of Pharmaceutical Crystal Engineering & Technology, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, China; [6] State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, Laboratory of Pharmaceutical Crystal Engineering & Technology, East China University of Science and Technology, Shanghai, 200237, China

年份：2025

外文期刊名：SSRN

收录：EI(收录号：20250522425)

语种：英文

外文关键词：Boltzmann equation - Conformations - Crystallization kinetics - Drug products - Engineering research - Molecular biology - Molecular physics - Polymorphism - Potential energy

摘要：The elusive nature of ‘disappearing polymorphs’ poses significant challenges in pharmaceutical development. This study investigates Rotigotine (RTG) Form I – a classic disappearing polymorph – through integrated conformational analysis and crystallization kinetics. By combining potential energy surface scans (B3LYP-GD3(BJ)/6-311G**) with lattice energy calculations, we demonstrate that Form II’s thermodynamic dominance (ΔG = -22.17 kJ/mol at 298 K) arises from packing efficiency (packing coefficient: 0.675 vs Form I's 0.65), despite Form I's lower conformational energy (global minimum). Solution-phase Boltzmann distributions reveal near-equivalent populations of Form I/II conformers ( ? 2025, The Authors. All rights reserved.