Division of Pharmaceutical Sciences, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, United States of America.
Division of Pharmaceutical Sciences, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, United States of America; Natoli Institute for Industrial Pharmacy Research and Development, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, United States of America.
Eur J Pharm Sci. 2019 Mar 15;130:215-224. doi: 10.1016/j.ejps.2019.01.039. Epub 2019 Feb 1.
The present report demonstrates a quality by design approach to understand and optimize self-nanoemulsifying orodispersible films (SNEODF) of captopril for hypertension. A central composite experimental design was used to study the formulation parameters effects (primary emulsion, aqueous phase, and surfactant) on the film properties (globule size, film burst, adhesion, Young's moduli, disintegration time, tensile strength and dissolution). Principle component analysis (PCA) and principle component regression (PCR) were employed to identify and quantify the effects of formulation variables and physico-mechanical properties of the film on the drug permeability. PCA classified three distinct groups of film formulations based on their composition and properties. PCR quantified the impact of main variables, their interactions, and square effects on the drug permeability. The main effect of the aqueous phase exhibited a negative impact, while that of flux and tensile strength showed a positive impact on the permeability. Interactions of primary emulsions with disintegration time and tensile strength displayed a synergistic impact. Interactions of aqueous phase with flux, Young's moduli, and tensile strength, as well as between Young's moduli and tensile strength showed a significant positive effect on the permeability. A negative correlation of square effects of primary emulsion and flux, and a positive square effect of Young's moduli confirmed their non-linear influence on the drug permeability across porcine buccal mucosa. This research work demonstrates application of design of experiment and multivariate methods to achieve targeted product quality of captopril (SNEODF) having improved permeability and pH independent release profile.
本报告展示了一种质量源于设计的方法，用于理解和优化卡托普利的自微乳给药口腔分散膜（SNEODF），以治疗高血压。采用中心复合实验设计研究了制剂参数（初乳、水相和表面活性剂）对膜性能（粒径、膜破裂、附着力、杨氏模量、崩解时间、拉伸强度和溶出度）的影响。采用主成分分析（PCA）和主成分回归（PCR）来识别和量化制剂变量和膜的物理力学性能对药物渗透性的影响。PCA 根据膜的组成和性能将膜配方分为三个不同的组。PCR 量化了主要变量、它们的相互作用和二次项对药物渗透性的影响。水相的主要效应表现出负向影响，而通量和拉伸强度的主要效应表现出正向影响。初乳与崩解时间和拉伸强度的相互作用显示出协同作用。水相与通量、杨氏模量和拉伸强度之间以及杨氏模量和拉伸强度之间的相互作用对药物渗透性有显著的正向影响。初乳和通量的二次项效应呈负相关，杨氏模量的二次项效应呈正相关，证实了它们对猪口腔黏膜透过性的非线性影响。这项研究工作展示了实验设计和多元方法的应用，以实现卡托普利（SNEODF）的目标产品质量，具有改善的渗透性和 pH 依赖性释放特征。
