Multivariate Methods in the Development of a New Tablet Formulation: Excipient Mixtures and Principal Properties

Multivariate Methods in the Development of a New Tablet Formulation: Excipient Mixtures and Principal Properties
Jon Gabrielsson A1, Michael Sjàstràm A1, Nils-Olof Lindberg A2, Ann-Christin Pihl A2, Torbjàrn Lundstedt A3
Drug Development and Industrial Pharmacy
Publisher: Taylor & Francis
Issue: Volume 32, Number 1
A1 Research Group for Chemometrics, Department of Chemistry, Ume¬ University, SE-901 87, Ume¬, Sweden
A2 Pharmacia AB, Consumer Healthcare, Box 941, SE-251 09, Helsingborg, Sweden
A3 Department of Medicinal Chemistry, Uppsala University, Box 574, 751 23, Uppsala, Sweden
A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material.
The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents).
As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.
Mixture design, D-Optimal, Excipient, Tablet formulation, PCA, PLS
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