DOE处方开发.doc

Design of Experiments for Formulation DevelopmentSource: Pharmaceutical TechnologyBy: Ruey-ching Hwang, PhD, Donna L. KowalskiOriginally published: December 1, 2005 All pharmaceutical products are formulated to specific dosage forms for drugs to be effectively delivered to patients. Typical pharmaceutical dosage forms include oral tablets, capsules, solutions, suspensions, topical ointments, gels, and solutions, and injections for intravenous (IV), intramuscular (IM), or subcutaneous (SC) administration. In addition, various drug delivery systems have been developed for transdermal, intranasal, and pulmonary deliveries. Different dosage forms require different pharmaceutical technologies and usually present different technical challenges for formulation development. Because of the complex technical challenges scientists encounter during formulation development, it is important to use an effective methodology. Design of experiments (DOE) and statistical analysis have been applied widely to formulation development, and are useful in process optimization and process validation. The major advantage of using DOE to develop formulations for pharmaceutical products is that it allows all potential factors to be evaluated simultaneously, systematically, and quickly. Using DOE, one can evaluate the effect of each formulation factor on each response (and possibly the interaction effects between factors) and identify the critical factors based on statistical analysis. Once the critical factors have been identified, the optimal formulation can be defined by using proper DOE to optimize the levels of all critical factors. The manufacturing process also can be developed and optimized in the same fashion. When the formulation and manufacturing process of a pharmaceutical product are optimized by a systematic approach using DOE, scale-up and process validation can be very efficient because of the robustness of the formulation and manufacturing process. This article uses tablet