Food and Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, St. Louis, Missouri 63101, USA.
J Pharm Sci. 2011 Nov;100(11):4934-42. doi: 10.1002/jps.22673. Epub 2011 Jun 23.
Dissolution testing is an important technique used for development and quality control of solid oral dosage forms of pharmaceutical products. However, the variability associated with this technique, especially with USP apparatuses 1 and 2, is a concern for both the US Food and Drug Administration and pharmaceutical companies. Dissolution testing involves a number of variables, which can be divided into four main categories: (1) analyst, (2) dissolution apparatus, (3) testing environment, and (4) sample. Both linear and nonlinear models have been used to study dissolution profiles, and various mathematical functions have been used to model the observed data. In this study, several variables, including dissolved gases in the dissolution medium, off-center placement of the test tablet, environmental vibration, and various agitation speeds, were modeled. Mathematical models including Higuchi, Korsmeyer-Peppas, Weibull, and the Noyes-Whitney equation were employed to study the dissolution profile of 10 mg prednisone tablets (NCDA #2) using the USP paddle method. The results showed that the nonlinear models (Korsmeyer-Peppas and Weibull) accurately described the entire dissolution profile. The results also showed that dissolution variables affected dissolution rate constants differently, depending on whether the tablets disintegrated or dissolved.
溶出度试验是一种用于开发和质量控制的固体口服药物制剂的重要技术。然而，与该技术相关的可变性，特别是与美国药典仪器 1 和 2 相关的可变性，是美国食品和药物管理局和制药公司都关注的问题。溶出度试验涉及许多变量，可以分为四个主要类别：（1）分析员，（2）溶出仪，（3）测试环境，和（4）样品。线性和非线性模型都被用于研究溶出曲线，并且各种数学函数被用于模拟观察到的数据。在这项研究中，包括溶解介质中的溶解气体、测试片剂的偏心放置、环境振动和各种搅拌速度在内的几个变量都被建模。使用美国药典桨法，Higuchi、Korsmeyer-Peppas、Weibull 和 Noyes-Whitney 方程等数学模型被用于研究 10 毫克泼尼松片剂（NCDA #2）的溶出曲线。结果表明，非线性模型（Korsmeyer-Peppas 和 Weibull）能够准确地描述整个溶出曲线。结果还表明，溶出度变量对溶出速率常数的影响不同，这取决于片剂是否崩解或溶解。
