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 (D90- 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.