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. 2008;9(2):620-7.
doi: 10.1208/s12249-008-9095-z. Epub 2008 May 6.

Rapid development and optimization of tablet manufacturing using statistical tools

Eutimio Gustavo Fernández  1 , Silvia Cordero, Malvina Benítez, Iraelio Perdomo, Yohandro Morón, Ada Esther Morales, Milagros Gaudencia Arce, Ernesto Cuesta, Juan Lugones, Maritza Fernández, Arturo Gil, Rodolfo Valdés, Mirna Fernández
Affiliations

Rapid development and optimization of tablet manufacturing using statistical tools

Eutimio Gustavo Fernández et al. AAPS PharmSciTech. 2008.

Abstract

The purpose of this paper was to develop a statistical methodology to optimize tablet manufacturing considering drug chemical and physical properties applying a crossed experimental design. The assessed model drug was dried ferrous sulphate and the variables were the hardness and the relative proportions of three excipients, binder, filler and disintegrant. Granule properties were modeled as a function of excipient proportions and tablet parameters were defined by the excipient proportion and hardness. The desirability function was applied to achieve optimal values for excipient proportions and hardness. In conclusion, crossed experimental design using hardness as the only process variable is an efficient strategy to quickly determine the optimal design process for tablet manufacturing. This method can be applied for any tablet manufacturing method.

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Figures

Fig. 1
Fig. 1
Cox trace graphs for a tap density (g/cm3) and b bulk density (g/cm3) of granules
Fig. 2
Fig. 2
Principal component analysis for granule properties without Carr’s Index inclusion (Score plot). Cluster analysis by Nearest Neighbor method and Squared Euclidean metric distance
Fig. 3
Fig. 3
Biplot graph (scores and loading) for granules properties not including Carr’s Index
Fig. 4
Fig. 4
Dissolution profile for tablets elaborated according to run 1 belongs to crossed experimental design. 1, 2,….,6 dissolution vessels
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