Fredrik Nicklasson

Multivariate Methods in the Development of a New Tablet Formulation

Abstract The overall objective of this article is to use an efficient approach to find a suitable tablet formulation for direct compression. By using traditional approaches to statistical experimental design in tablet formulation, the number of experiments quickly grows when many descriptive variables or many excipients are included. To facilitate the screening process, a multivariate design, which allows a systematical evaluation of a large number of excipients with a limited number of experiments, was implemented. Formulations with acceptable values for disintegration time and crushing strength were obtained with some of the formulations in the present study. The multivariate experimental design strategy yielded PLS models that will be used to identify a region of interest for the optimization. The strategy is general and can be applied in many different areas of pharmaceutical research and development.

Multivariate methods in the development of a new tablet formulation: optimization and validation.

In a previous study of the development of a tablet formulation approximately 100 excipients were characterized in screening experiments using multivariate design. Acceptable values for important responses were obtained with some of the formulations. The relationships between the properties of the excipients and the responses were evaluated using PLS. In this study additional experiments were performed in order to validate models obtained from the screening study and to find a formulation of suitable composition with desired tablet properties. A formulation with the desired disintegration time was found with the additional experiments and the agreement between observed and predicted values was fair for the tablets that did disintegrate. A limitation of this study was that tablets from four experiments did not disintegrate within the set time limit. The lack of agreement between observed and predicted values of these four experiments was probably due to the nature of one of the factors in the design. Considering the reduced experimental design the results are still encouraging.