Modelling the Manufacturing Process and Product Performance of Roller Compacted Pharmaceutical Tablets

Direct compaction, dry granulation and wet granulation are the three processes typically employed to produce pharmaceutical tablets. Dry granulation is used to improve content uniformity, dissolution times and stability, by aggregating particles in granules without water addition. This is done by compressing the powders (active ingredient, excipients, etc.), previously mixed, in a roller compactor. The ribbon produced is then milled to the required granule size before being compressed in  a tablet press.

In this presentation, a flowsheet of a tablet manufacturing process via dry granulation is developed. Literature models for roller compaction (Johanson, 1965; Reynolds et al, 2010) and milling (Vogel and Peukert, 2005) are used. A new model for tablet compaction is developed to predict tablet porosity and tensile strength as a function of tablet compaction pressure. This model is based on concepts presented in the literature previously (Wu et al, 2006; Farber et al, 2008). In order to evaluate the influence of material properties and process operating conditions on the produced tablet, a model for tablet dissolution is also developed. This model extends work done previously (Wilson et al, 2012), and it relates the tablet porosity and material properties to the tablet erosion rate and dissolution time.

The individual unit operations in the process are validated against experimental data. The validated process flowsheet is used to perform sensitivity studies to explore the effect of roller compaction operating pressure and tablet compaction pressure on ribbon and tablet porosity, tablet tensile strength and dissolution time.

References

Johanson JR (1965) A rolling theory for granular solids. ASME, Journal of Applied Mechanics Series E 32, 842-848

Reynolds G, Ingale R, Roberts R, Kothari S, Gururajan B (2010) Practical application of roller compaction process modelling. Computers and Chemical Engineering 34, 1049–1057

Vogel L, Peukert W (2005) From single particle impact behaviour to modelling of impact mills. Chemical Engineering Science 60, 5164 – 5176

Wu C-Y, Best SM, Bentham AC, Hancock BC, Bonfield W (2006) Predicting the tensile strength of compacted multi-component mixtures of pharmaceutical powders. Pharmaceutical Research 23, 1898-1905

Farber L, Hapgood KP, Michaels JM, Fu X-Y, Meyer R, Johnson M-A, Li F (2008) Unified compaction curve model for tensile strength of tablets made by roller compaction and direct compression. International Journal of Pharmaceutics 346, 17–24

Wilson D, Wren S, Reynolds G (2012) Linking dissolution to disintegration in immediate release tablets using image analysis and a population balance modelling approach. Pharmaceutical Research 29, 198-208