Tablet Geometry Research Articles

Control of Poorly Soluble Drug Dissolution in Conditions Simulating the Gastrointestinal Tract Flow. 1. Effect of Tablet Geometry in Buffered Medium

The dissolution rate of a solid drug from the gastrointestinal (GI) tract is affected by the properties and flow dynamics of the liquid medium surrounding the tablet, as well as by the chemical nature of the drug. In this study, naproxen was used as a poorly soluble model drug. The dissolution medium was buffered with acetate, citrate, or phosphate buffer of varied concentrations and pH. GI flow conditions around a stationary tablet were simulated in a laminar flow device by anchoring the tablet on the floor of its channel having a rectangular cross section. Fresh, buffered solution was passed across the tablet and the effluent was collected for analysis and calculation of the dissolution rate. The dissolution rate was found to vary nonlinearly with the exposed tablet height, reaching a maximum at a tablet height approximately half the channel height. This maximum rate was attributed to an optimal combination of (1) eddy mixing and local turbulence generated by the flow impingement on the bluff object (tablet) and (2) the exposed tablet surface area available for dissolution. This effect was further confirmed by using dye-enhanced visual analysis of flow patterns at varied flow rates and exposed tablet heights. Elevation of the tablet to approximately the channel half-height significantly magnified the dissolution rate increase observed on exposure to buffered medium. Thus, tablet height and exposed surface area are major factors in determining dissolution rate, especially in conditions where the dissolving species reacts with the solvent. These results suggest that standard in vitro dissolution rate methods do not qualitatively indicate incremental changes in rate with altered tablet geometry or dissolution medium.

An Examination of Assumptions Underlying the First-Order Kinetic Model for Release of Water-Soluble Drugs from Dicalcium Phosphate Dihydrate Matrices

It has been shown that the release of highly water-soluble drugs from compressed dicalcium phosphate dihydrate matrices follows first-order kinetics (1). Good correlation between the rate constant and tablet geometry (2) was also reported. However, the rate constants for different geometry could not be predicted accurately by using the constants obtained for cylindrical tablets. In this work the assumptions regarding the surface area, porosity, and inertness of the drug toward the matrix have been tested using simple experimental designs and techniques such as porosimetry, electron microscopy, and differential scanning calorimetry. No interactions between the drug and the matrix were observed. The assumptions regarding porosity/void volume seemed to hold. Using water as a penetrant gave better estimate of porosities than those obtained using mercury. The assumption regarding surface area needs correction; however, a better alternative has not been proposed.

The impact fracture wear test: A novel method of tablet evaluation

Tablet strength is usually determined by the diametral compression test or by the indentation hardness test. However, the limited data available from such tests make the development of a new test desirable. For this purpose, this report describes the development of a modified friability test, named the ‘impact fracture wear test’. It provides data which are not solely dependent upon the greatest flaw in the tablet and it stresses the tablet in a manner similar to subsequent processing. The relationship between tablet half-life ( t 50), a strength parameter, and relative density, and the effects of dwell time and particle size, were found to be similar to those described in the literature. The wear of castings of Plaster of Paris fits a first-order kinetic model well. The wear of compacts of sodium chloride deviates increasingly from first-order kinetics with increasing grain size and porosity. These deviations may be correlated with the non-homogeneity of tablet strength, the effects of tablet geometry, and of changes in process variables such as humidity, lubrication, preconsolidation, and storage time. Examination of the tablet and its wear fragments during the test provides information about the deformation and fracture characteristics of the material.