Investigations into the Relationship Between Drug Properties,Filling, and the Release of Drugs from Hard Gelatin Capsules Using Multivariate Statistical Analysis

Purpose. The aim of the present work is to identify complex relationships between formulation variables and dosage form properties to aid the development of hard gelatin capsules. Methods. Multivariate statistical analysis was employed based on a statistical design, which considered drug solubility, particle size and concentration, type and concentration of filler and disintegrant, and concentration of standard lubricant and glidant as the main influence factors. Both the filling properties of the formulations and the disintegration/dissolution properties of the capsule content were studied. Results. From the two multivariate statistical methods used, nonparametric canonical analysis proved to be the superior method to deal with the complex information included in the data. While the filling performance of the formulation could clearly be attributed to the formulation variables such as drug particle size, type of filler, concentration of drug and glidant, the disintegration of the capsules and the dissolution of the drugs was not strongly related to the formulation variables chosen. In this respect as a trend, the drug solubility, and the type of disintegrant and filler appear to be more important factors. Conclusions. Based on an appropriate number of experiments, organised in a statistical design, nonparametric canonical analysis can be used to identify relationships in a set of data that is grouped in influence and response variables to aid the development of a dosage form.     

The strength of bilayered tablets

The tensile strength of model materials (dicalcium phosphate dihydrate, microcrystalline cellulose and pregelatinised starch) compacted to form tablets in the form of beams consisting of two layers of equal thickness has been determined by three-point loading. The values of the tensile strength of the materials were sometimes higher and sometimes lower than the tensile strength of beams of the same thickness composed of a single material. Correction of the values for the tensile strength of the layered beams for the differences in the elasticity of the materials in the layered tablets failed to correct for these differences, as did considering the layered beams as beams of half thickness. For a layered tablet with pregelatinised starch at the bottom and microcrystalline cellulose at the top, the value of the tensile strength recorded appeared to be that of the microcrystalline cellulose as the fracture propagated across the boundary between the layers and into microcrystalline cellulose. What appeared to be the important factor was the way the failure of the beam crossed the interface between the two layers.