Solid State Pharmaceutics Lab, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar, Mohali, Punjab, 160 062, India.
Biocon Bristol Myers Squibb Research & Development Center (BBRC) Syngene, Bangalore, India.
Eur J Pharm Sci. 2021 Jun 1;161:105782. doi: 10.1016/j.ejps.2021.105782. Epub 2021 Mar 3.
Milling may cause undesired changes in crystal topology, due to exposure of new facets, their corresponding functional groups and surface amorphization. This study investigated effect of milling induced surface amorphous content and chemical environment on moisture sorption behavior of a model hydrophilic drug, Terbutaline Sulphate (TBS). A Dynamic Vapor Sorption (DVS) based analytical method was developed to detect amorphous content, with LOD and LOQ of 0.41% and 1.24%w/w, respectively. The calibration curve gave a linear regression of 0.999 in a concentration range of 0-16.36%w/w amorphous content plotted against surface area normalized % weight change, due to moisture sorption. TBS was milled using air jet mill at 8 Bars for 3 cycles (D- 3.46µm) and analyzed using the validated DVS method prior to and post conditioning. The moisture sorption was higher in case of milled unconditioned TBS. Molecular Dynamics Simulation (MDS) was performed to identify the cause for increased moisture sorption due to altered surface environment or amorphous content. The results implied that the new planes and functional groups exposed on milling had negligible contribution to moisture sorption and the higher moisture sorption in milled unconditioned TBS was due to surface amorphization. Conditioning under elevated humidity recrystallized the milling-induced surface amorphous content and led to decreased moisture sorption in milled conditioned TBS.
研磨可能会导致晶体拓扑结构发生意想不到的变化，因为新的晶面会暴露出来，它们对应的官能团和表面非晶化。本研究考察了研磨诱导的表面非晶含量和化学环境对模型亲水性药物硫酸特布他林（TBS）吸湿性的影响。开发了一种基于动态蒸汽吸附（DVS）的分析方法来检测非晶含量，其检测限和定量限分别为 0.41%和 1.24%w/w。校准曲线在 0-16.36%w/w 非晶含量范围内与因水分吸附而导致的表面积归一化重量变化呈线性回归，相关系数为 0.999。TBS 用空气喷射磨在 8 巴下研磨 3 个循环（D-3.46µm），并在预处理和后处理之前使用经过验证的 DVS 方法进行分析。未处理的研磨 TBS 的吸湿性更高。进行了分子动力学模拟（MDS），以确定由于表面环境或非晶含量的改变而导致吸湿性增加的原因。结果表明，研磨过程中暴露的新平面和官能团对吸湿性的贡献可以忽略不计，而未处理的研磨 TBS 中吸湿性较高是由于表面非晶化。在高湿度条件下进行预处理可使研磨诱导的表面非晶含量重结晶，并导致研磨预处理 TBS 的吸湿性降低。
