Prediction of the ease of subdivision of scored tablets from their physical parameters.
At present, the ease of subdivision of scored tablets is estimated in vivo. In order to replace such in vivo testing and to develop a surrogate test which uses in vitro techniques, the association between physical parameters of scored tablets and their ease of subdivision was studied. The physical properties of 23 brands of scored tablets of which their ease of subdivision in vivo was known were established. Statistical modeling using a logistic regression model was used to fit the data and estimate the contribution of each physical parameter to the goodness of the fit. For scored oblong tablets, the critical parameters for their ease of subdivision are: diameter; diameter/width ratio; depth of score line and resistance to crushing. Criteria for each of these parameters were derived. All criteria need to be complied with to guarantee sufficient ease of subdivision of scored oblong tablets. For scored round tablets the critical parameters, in decreasing order of importance, for their ease of subdivision, are: resistance to crushing, diameter, score mark (one- or two-sided), and shape (flat or biconvex). A five-parameter predictive model was developed, showing excellent discrimination. For development, the proposed surrogate tests are sufficiently reliable. For release testing and stability studies, resistance to crushing of a scored tablet is a reliable predictor of its ease of subdivision.
van der Steen
Koos C
KC
RijksInstituut voor Volksgezondheid en Milieu RIVM (National Institute for Public Health and the Environment), Bilthoven, The Netherlands.
Frijlink
Henderik W
HW
Schipper
C Maarten A
CM
Barends
Dirk M
DM
D002985:Clinical Protocols; D006801:Humans; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards*
D013607:Tablets