Influence of polymer content on stabilizing milled amorphous salbutamol sulphate.

The study investigates the influence of polyvinyl pyrrolidone (PVP) concentration on stabilizing the amorphous form of salbutamol sulphate (SS) before and after storage under ambient and elevated humidity conditions. Different mass ratios of SS and PVP (0-90wt%) were co-milled using a planetary ball mill. X-ray powder diffraction (XRPD), high sensitivity differential scanning calorimetry (HSDSC), dynamic vapor sorption (DVS), infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and Raman microscopy (RM) were used to analyze the stability of the co-milled mixtures against heat and humidity treatments as well as storage at different humidity conditions. Prior storage, DSC and DVS analyses revealed that re-crystallization of amorphous SS was suppressed above PVP content of 33 wt%. Probable hydrogen bond interaction between SS and PVP was found in FT-IR analysis. XRPD diffractograms and SEM analysis showed stability against re-crystallization was achieved in the co-milled mixtures with a minimum PVP content of 80 wt% after storage. Homogeneous distribution of SS and PVP from RM analysis showed fine clustering of SS and PVP, suggesting the formation of an amorphous dispersion at molecular level. The results provide insights on the application of thermal and humidity treatments, accelerated stability testing and investigations on drug-excipient interactions to predict the minimum ratio of an excipient for stabilizing the amorphous state of a milled API. Copyright (c) 2010 Elsevier B.V. All rights reserved.