Weon K Y, Lee K T, Seo S H
Galenical Research Team/R&D Center, Handok Pharmaceuticals Co, Ltd, Taeso-myon, Chungbuk Province, Korea.
Arch Pharm Res. 2000 Oct;23(5):507-12. doi: 10.1007/BF02976581.
This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1X2> X2X2> X2X3> X3X3> X1X3> X1X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.
本研究旨在通过适当的实验设计改善现有制剂的物理和药学特性。此处所述工作涉及采用直接压片法制备含包衣颗粒形式罗红霉素的分散片。在本研究中，采用2(3)析因设计作为筛选试验模型，采用与响应面法相关的中心复合设计(CCC)作为优化研究模型，以开发和优化罗红霉素分散片的合适制剂。研究的三个自变量为功能性辅料，如粘合剂(X1)、崩解剂(X2)和润滑剂(X3)。研究了这些变量对片剂以下响应的影响：硬度(Y1)、脆碎度(Y2)和崩解时间(Y3)。在每个设计的中心水平进行三次重复实验，以独立计算实验误差并检测响应面中的任何曲率。这使得能够客观地选择最佳制剂。得出了每个因素对所有响应变量的影响顺序为X3> X2> X1> X1X2> X2X2> X2X3> X3X3> X1X3> X1X1，并生成了每个响应变量的模型方程。据此使用这些模型方程计算出配方的优化组成，并通过后续的验证研究进行了确认。结果，本研究证明了使用系统的制剂优化过程以有限的实验开发罗红霉素分散片剂的效率和有效性。
