Role of surface molecular environment and amorphous content in moisture sorption behavior of milled Terbutaline Sulphate.

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.