(317a) 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