title: Design space construction of multiple dose-strength tablets utilizing bayesian estimation based on one set of design-of-experiments.
abstract: 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 surfaces, 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.
authors.affiliation: Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1–12–1 Shinomiya, Hiratsuka, Kanagawa 254–0014, Japan. maeda.jin.d2@daiichisankyo.co.jp
authors.forename: Jin
authors.initials: J
authors.lastname: Maeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D001499:Bayes Theorem; D001993:Bronchodilator Agents / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D054327:Lubricants / Q000737:chemistry; D008956:Models, Chemical; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013806:Theophylline / Q000737:chemistry
chemical_list: D001993:Bronchodilator Agents; D005079:Excipients; D054327:Lubricants; D013607:Tablets; D013806:Theophylline