Predicting Tablet Strength from the Wet Granulation Conditions via the Unified Compaction Curve

Abstract

Tablets make up approximately one third of all drug dosage forms which makes tablet manufacture a common process in the pharmaceutical industry. The unified compaction curve [1] is a model developed initially to look at the impact of the roller compaction conditions on the tablet strength. The tensile strength of the tablets made from formulations containing at least 50% microcrystalline cellulose produced at roller compaction pressures were measured and the profiles were collapsed into a single master “unified compaction curve” (UCC). This allowed for the tablet strength to be predicted from the roller compaction condition and formulations and target the required tablet strength criterion set by standards or specifications [1].The unified compaction curve was applied to investigate the effects of the wet granulation conditions in a 5L Key granulator on the tablet tensile strength. The study was based on a placebo formulation comprising of 50wt% microcrystalline cellulose, 50wt% lactose and a 5w/v% PVP (K90) binder solution. The effects of the liquid level (20-50wt%), wet massing time (0-10minutes), binder flow rate (130g/min and 280g/min) and impeller speed (150, 285 and 600rpm) on the tablet strength were explored. Scale-down experiments to a 1L mixer bowl were also conducted. Tablets were produced on a single station carver press with controlled force.A series of compaction profiles were created to represent the relationship between the tablet tensile strength, compaction pressure and the granulation condition. By fitting the unified compaction curve model to the data using a shifting intercept approach, the profiles exploring each granulation condition collapsed onto a single master curve which predicts the tablet strength as a function of the liquid level, wet massing time or the binder flow rate. Increasing the liquid level and/or wet massing time caused a reduction in the tablet hardness when compressed at the same compaction force, and the reduction is postulated to be proportional to the effective compaction forces experienced during granulation, PWGC. The PWGC data further collapses onto a single master curve which is solely a function of the total number of impeller revolutions. Further characterization of the granules produced at these conditions showed that the UCC intercept parameter, PWGC was inversely proportional to the granule porosity, linking the granule microstructure directly and quantitatively to the tablet strength during compaction. This is a significant finding that will allow formulators to optimize tablet hardness via a simple adjustment to the granulation conditions.