Michael S. Bergren

An automated controlled atmosphere microbalance for the measurement of moisture sorption

Abstract A controlled atmosphere microbalance system has been constructed for the measurement of moisture sorption in pharmaceutical materials. The system is automated, and the user can program arbitrary changes of relative humidity (RH) under computer control. The sample is suspended in an isothermal chamber at 20–25°C, and the RH is regulated from 1 to 98% RH by adjusting the flows of dry and moist gas. A commercial sensor system is used to determine the relative humidity of the flowing gas. Over most of the range, the absolute RH accuracy is ± 3%, the RH reproducibility is ± 1%, and the RH stability is ± 0.2%. Sample masses as large as 1 g can be accommodated. For a typical sample mass of 10 mg, the reproducibility of the weight uptake measurement is typically better than 0.05% of the dry weight over the entire working range of relative humidity. The data collection software employs a weight stability criterion for equilibrium to allow data collection at the maximum rate permitted by the sorption kinetics of the material under investigation. Three examples are presented of applications to pharmaceutical powders.

Analysis of solvent residues in pharmaceutical bulk drugs by wall-coated open tubular gas chromatography

A simple general method for the determination of solvent residues in drugs is described. The procedure is based on wide-bore wall coated open tubular (WCOT) gas chromatographic analysis of bulk drug solutions. The use of wide-bore WCOT columns with chemically crosslinked methyl silicone stationary phases offers improvements in specificity and sensitivity over earlier packed-column methods. The factors that influence method accuracy are discussed, including a consideration of instrumental and matrix contributions to the linearity and bias of the method. Some problems with interferences peculiar to benzyl alcohol are reported.

Investigation of the relationship between melting-related parameters and in vitro drug release from vaginal suppositories

The effect of temperature on drug release from meteneprost potassium vaginal suppositories was investigated using a dissolution test based on the USP I apparatus. Comparison of the dissolution results with the DSC melting behaviour revealed that drug release was extremely slow until melting of the suppository was essentially complete. The melting behaviour of the meteneprost potassium suppositories was also varied by preparing suppositories from bases with higher and broader melting ranges. The observed dissolution behaviour (at 37 degrees C) confirmed that drug release increased as the melting temperature of a particular suppository decreased. Differential scanning calorimetry, viscosity and dilatometry methods were used to characterize the suppository melting process. The effects of suppository melting range, melt temperature and composition were investigated with respect to in vitro drug release. Methodology for the HPLC determination of meteneprost in suppositories and in dissolution media are also reported.