Evaluation of the Functional Equivalence of Crospovidone NF from Different Sources. I. Physical Characterization

Abstract

In the past two decades, three categories of newer disintegrants have come into widespread use. These substances are a synthetic polymer (crospovidone), chemically modified starch (sodium starch glycolate) and cellulose (croscarmellose sodium). Multiple suppliers are now available for each category. Current NF monographs do not provide tests which reflect on their functionality and one cannot assume reliable performance of disintegrants from different sources meeting NF standards. The objective of this study was to identify differences in physical properties thought to be related to functionality among crospovidones from multiple sources. Physical properties examined included particle size and distribution, surface area, porosity and surface morphology. Disintegration and dissolution were performed on a model tablet formulation using either an insoluble or a soluble filler. Substantial differences in particle size and distribution, surface area, porosity and surface morphology were observed which correlated with differences in disintegration time and dissolution rate of the model drug from an insoluble tablet core. None of the differences in physical properties resulted in any differences in the disintegration or dissolution of the model drug from a soluble tablet core.

Novel use of superdisintegrants as viscosity enhancing agents in biocompatible polymer films containing griseofulvin nanoparticles

“…In fact, the degree of substitution, cross-linking etc. may also vary, thus changing the properties of these compounds and hence a potential brand to brand variation could exist as a function of slightly differing properties of superdisintegrants produced by different companies [64][65][66][67]. While important, detailed investigation of the impact of such variation is considered outside the scope of the current investigation.…”

The Influence of Product Brand-to-Brand Variability on Superdisintegrant PerformanceA Case Study with Croscarmellose Sodium

“…[7] The apparatus consists of a sample holder and a liquid holding vessel that is set on an electronic balance. These two parts of the apparatus are adjusted at the same horizontal level and connected by a plastic tube so that water can flow freely from one side to the other.…”

“…In another study, differences in particle size, surface area, and porosity among several sources of crospovidone were found to be related to differences observed in disintegration and dissolution of a model drug from an insoluble filler system. [7] Later, significant differences were found in settling volume, rate and extent of liquid uptake, and force generated by the crospovidones. [8] Such reports serve to underscore both the need for and the difficulty in developing efficient and effective discriminatory methodology and suggest that different classes of superdisintegrants may require different methodologies.…”

Evaluation of Hydroperoxides in Common Pharmaceutical Excipients

“…The physical properties of excipients have received the most attention, and the topics of excipient functionality testing and multisource excipient equivalence have been largely discussed in this context. 1,2 However, the chemical impurity profiles of excipients have not, in general, received similar attention. Excipient chemical impurity profiles can be very important in influencing the long-term chemical stability performance of the formulated drug product, particularly if an oxidatively sensitive drug is being formulated.…”