Possible ambiguities when testing viscosity in compendial monographs - characterisation of grades of cellulose ethers.

Abstract

The European Pharmacopoeia (Ph. Eur.) monographs for the water-soluble cellulose ethers require viscosity determination, either in the "Tests" section or in the non-mandatory "Functionality-related characteristics" section. Although the derivatives are chemically closely related and used for similar applications, the viscosity tests strongly differ. Some monographs generically speak of the rotating viscometer method (2.2.10) and a fixed shear rate (e.g. 10 s-1), which would necessitate an absolute measuring system, while others recommend the capillary viscometer method for product grades of less than 600 mPa∙s and the rotating viscometer method and given operating conditions for grades of higher nominal viscosity. Viscometer methods also differ between the United States Pharmacopeia/National Formulary (USP/NF) and the Japanese Pharmacopoeia (JP) monographs. In addition, for some cellulose ethers the tests sometimes diverge from one pharmacopoeia to the other, although the three compendiums are in a harmonisation process. But the main issue is that the viscometer methods originally employed by the product manufacturers are often not those described in the corresponding monographs and generally vary from one manufacturer to the other. The aim of this study was therefore to investigate whether such a situation could invalidate the present pharmacopoeial requirements. 2 per cent solutions of several viscosity grades of hydroxyethylcellulose, hypromellose and methylcellulose were prepared and their (apparent) viscosity determined using both relative and absolute viscometer methods. The viscometer method used not only affects the measured viscosity but experimental values generally do not correspond to the product nominal viscosities. It emerges that, in contrast to Newtonian solutions (i.e. those of grades of up to ca. 50 mPa∙s nominal viscosity), some of the viscometer methods currently specified in the monographs are not able unambiguously to characterise the grades exhibiting non-Newtonian behaviour. It is also concluded that, unless the various manufacturers redefine their product viscosity grades using a single compendial test, two strategies could be adopted, both based on the operating conditions specified in the labeling (i.e those of the manufacturer), the test appearing either in the mandatory section if this is acceptable to the pharmacopoeia (like in some USP/NF monographs) or, for the Ph. Eur., in the "Functionality-related characteristics" section.