Design Space Construction of Multiple Dose-Strength Tablets Utilizing Bayesian Estimation Based on One Set of Design-of-Experiments

Jin Maeda, Tatsuya Suzuki, Kozo Takayama
2012 Chemical and pharmaceutical bulletin  
Design spaces for multiple dose strengths of tablets were constructed using a Bayesian estimation method with one set of design of experiments (DoE) of only the highest dose-strength tablet. The lubricant blending process for theophylline tablets with dose strengths of 100, 50, and 25 mg is used as a model manufacturing process in order to construct design spaces. The DoE was conducted using various Froude numbers (X 1 ) and blending times (X 2 ) for theophylline 100-mg tablet. The response
more » ... aces, design space, and their reliability of the compression rate of the powder mixture (Y 1 ), tablet hardness (Y 2 ), and dissolution rate (Y 3 ) of the 100-mg tablet were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. Three experiments under an optimal condition and two experiments under other conditions were performed using 50-and 25-mg tablets, respectively. The response surfaces of the highest-strength tablet were corrected to those of the lower-strength tablets by Bayesian estimation using the manufacturing data of the lower-strength tablets. Experiments under three additional sets of conditions of lower-strength tablets showed that the corrected design space made it possible to predict the quality of lower-strength tablets more precisely than the design space of the highest-strength tablet. This approach is useful for constructing design spaces of tablets with multiple strengths.
doi:10.1248/cpb.c12-00491 pmid:23124564 fatcat:cksbxbwvevho5h45i5aj3xf3ke