Environmentally Controlled Optical Microscopy for the Pharmaceutical Sciences

K E Y W O R D S environmental controlled light microscopy, pharmaceutical solids, amorphous transitions, stability, environmental control stage A C K N O W L E D G E M E N T S The authors wish to thank Sebastian Kaerger for his help in producing the spray dried salbutamol sulphate. A U T H O R D E TA I L S Dr Paul M. Young, Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK. Tel: +44 (0)1225 383103 Fax: +44 (0)1225 826114 Email: [email protected] Microscopy and Analysis (UK), 95, 5-7, 2003. ©2003 Rolston Gordon Communications. Flawil, Switzerland) to produce amorphous material (confirmed by X-ray powder diffraction). The influence of humidity on the recrystallisation of the amorphous salbutamol was investigated using a novel environmental control stage for optical microscopy (VGI 2000M, Surface Measurement Systems Ltd, London, UK). Briefly, the VGI stage operates by combining a dry and humidified gas flow (using two independent mass-flow controllers) in a sealed microscope stage. In addition, constant temperature of the stage was maintained by a Peltier-controlled water bath to eliminate condensation. Relative humidity was controlled by varying the dry to wet flow ratios (mass flow values) and monitored by a built-in thermometer and humidity meter. The whole system was computer controlled, allowing both static and gradient measurements. A schematic diagram of the equipment set-up and VGI microscope stage are shown in Figs 1 and 2, respectively. The VGI humidity probe and mass flow controllers were calibrated against a sodium chloride standard, which deliquesces at 75.3% RH at 25 ̊C. A small quantity of the amorphous salbutamol sulphate was quickly transferred to a glass slide, mounted on the VGI stage, sealed, and exposed to 0% RH for 4 hours. The VGI stage was positioned under a conventional Nikon transmission light microscope with a polarised-light filter, and imaged at a 160X magnification using a CCD camera attachment. The salbutamol sulphate was exposed to a humidity range of 0-90% RH at 10% RH increments. A pause of 100 minutes was instiEnvironmentally Controlled Optical Microscopy for the Pharmaceutical Sciences