(512j) Investigating the Crystallization Mechanism of Amorphous Budesonide and Salbutamol Sulfate

PURPOSE: Many low molecular weight amorphous materials will relax to their thermodynamically stable, crystalline form. The timescale of this transition is dependent on both temperature and solvent concentration. Therefore, understanding the kinetics of this transition over a wide range of temperatures and solvent concentrations is vital for the processing and storage of materials containing amorphous phases. In this study the crystallization of both hydrophilic (salbutamol sulfate) and hydrophobic (budesonide) drugs are investigated via vapor sorption techniques.

METHODS: Salbutamol sulfate (SS) and budesonide (BD) were made (partially) amorphous via milling. Dynamic gravimetric Vapor Sorption (DVS) was used to monitor the crystallization behavior of the two drugs over a wide range of temperatures. This was observed as a sharp mass loss when exposed to high vapor concentrations. Water was used to crystallize SS, while ethanol was used to crystallize BD.

RESULTS AND DISCUSSION: When SS was exposed to water vapor concentrations above 42% relative humidity (RH) amorphous SS reverted to its crystalline form. This transition was monitored over a range of temperatures. Model-free mechanism analysis indicated SS crystallized in a one step, nth dimension Avrami-Erofeev process (n~0.5). Exposure to ethanol vapor above 55% P/Po at 25°C induced amorphous BD to crystallize. Ramping the ethanol vapor concentration from 0 to 95 % P/Po clearly showed vapor-induced glass transition and crystallization points.

CONCLUSIONS: The vapor-induced crystallization behavior of salbutamol sulfate (water vapor) and budesonide (ethanol vapor) was studied over a wide range of temperatures. Ethanol caused budesonide to crystallize above 55% P/Po at 25 °C. Mechanism modeling indicated a one-step Avrami-Erofeev process for water-induced salbutamol sulfate crystallization.