Our quest for an acceptable replacement for the defunct Knauer, Model 01.00 membrane osmometer continues. We have evaluated two Gonotec, Model 090B osmometers and found difficulty with both in obtaining reproducible readings when applying known hydrostatic pressures with the calibration rod. Compounding our difficulty in procuring suitable instrumentation is the current unavailability of appropriate semipermeable membranes. Nevertheless, we are continuing our search since the number average molecular weight (M/n) data that we have obtained for Dextran 70 and Dextran 40 have demonstrated that the HPLC-gel permeation chromatography (GPC) methodology in the proposed USP Monographs for the Dextrans gives correct M/n values. Furthermore, membrane osmometry has permitted an estimate of the upper limit of M/n for Hetastarch, <46, 700> sigma; only an upper limit could be measured due to the presence of low concentrations of lower molecular weight species that were membrane permeable. This value is proving extremely important in resolving the conflict among M/n values being reported for innovator Hetastarch by manufacturers applying for approval of a generic Hetastarch and being reported by the innovator itself; all such reported Mn values derive from some sort of HPLC-GPC method. Clearly obtaining Mn values by membrane osmometry is not only important in understanding the physical/physiological properties of such colloid volume expanders but is also relevant in resolving regulatory issues.
