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 (0-10 minutes), binder flow rate (130g/min and 280g/min) and impeller speed (150, 285 and 600 rpm) 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 518 Thanh H. Nguyen et al. / Procedia Engineering 102 ( 2015 ) 517 -526 proportional to the effective compaction forces experienced during granulation, P WGC . The P WGC 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, P WGC 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.

Influence of Binding Solution Concentration, Drying Duration and Drying Temperature on Physiochemical Performance of Norfloxacin Granules and Tablets

“…Accordingly, the higher the concentration of the binder solution the harder will be the granules and the higher will be the compression force that needed for fragmentation and/or deformation to form compact formation. This finding is in agreement with that published by Nguyen et al [20]. .…”

“…It could be true that crushing strength of the granules tends to increase as a consequence of increasing the concentration of the binder solution; however, this might not correlates with the tablets strength [19,20]. The compression process results in a decrease in powder volume; owing to elastic and/or plastic deformation and the degree of particle attrition behaviors of the particle-particle bonds in the powder mass [21].…”

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“…The graph of absorbance vs. concentration for sitagliptin phosphate monohydrate was found to be linear in the concentration range of 0-10 µg/mL at 267 nm. The R 2 of the calibration curve was found to be 0.999, which concludes that it follows the Beers Lambert's law within this concentration range 13 . Infrared Spectroscopy: The FTIR spectrum of the API shown in Fig.…”

“…Wavelength of maximum absorbance (λ max ) of sitagliptin phosphate monohydrate was found to be 267 nm in distilled water 13 .…”

Functionality evaluation of co-processed excipients as diluents in tablets manufactured by wet granulation

“…The lowering of tensile strength of tablets formulated with C-PE as diluents may be associated with the inability of the diluents to exert their effect as directly compressible excipients in tablets formulated by wet granulation. Formulation studies have shown that directly compressible excipients tend to lose their compressibility when incorporated in tablet formulations by wet granulation (Nguyen et al, 2015). Tablet friability parameter was evaluated to measure the weakness of the tablet.…”