Investigation of Flow Properties of Powders by Means of a Uniaxial Tester, in Relation to Direct Tablet Compression

Abstract

ABSTRACTUnexpected poor flowability during commercial production of a direct compression tablet formulation initiated an investigation of the flow properties of the powder mixture and its components by means of a uniaxial tester. The failure function—a curve describing the strength of the powder bed as a function of the maximum main stress that has consolidated the bed—of the powder mixture and its components was determined. The drug was more cohesive than the filler, which was somewhat more cohesive than the powder mixture. Three excipients—a binder, a glidant and a lubricant—constituting 3.5 w/w% of the formulation improved the flowability of the mixture of active ingredient and filler. The failure function discriminated powder mixtures with poor flow from mixtures with medium or good flow. However, it was not possible to discriminate medium from good flow by means of the failure function. Attempts to correlate univariately the flow property parameters of the powder mixtures with particle size data or flow property data of included active ingredient and filler batches failed. Therefore a multivariate approach was tested. Principal component analysis (PCA) and projection to latent structures by means of partial least squares (PLS) were employed. An excellent PCA model was obtained with the flow properties of the powder mixture. A good PCA model of tableting performance—based on tablet weight variation and tablet machine speed—was obtained.