Drug Product Design, Worldwide Research, Development and Medical, Pfizer Inc., Groton, CT 06340, USA.
Drug Product Design, Worldwide Research, Development and Medical, Pfizer Inc., Groton, CT 06340, USA.
J Pharm Sci. 2023 Jul;112(7):1772-1793. doi: 10.1016/j.xphs.2023.03.014. Epub 2023 Mar 24.
The emulsion-based topical semisolid dosage forms present a high degree of complexity due to their microstructures which is apparent from their compositions comprising at least two immiscible liquid phases, often times of high viscosity. These complex microstructures are thermodynamically unstable, and the physical stability of such preparations is governed by formulation parameters such as phase volume ratio, type of emulsifiers and their concentration, HLB value of the emulsifier, as well as by process parameters such as homogenizer speed, time, temperature etc. Therefore, a detailed understanding of the microstructure in the DP and critical factors that influence the stability of emulsions is essential to ensure the quality and shelf-life of emulsion-based topical semisolid products. This review aims to provide an overview of the main strategies used to stabilize pharmaceutical emulsions contained in semisolid products and various characterization techniques and tools that have been utilized so far to evaluate their long-term stability. Accelerated physical stability assessment using dispersion analyzer tools such as an analytical centrifuge to predict the product shelf-life has been discussed. In addition, mathematical modeling for phase separation rate for non-Newtonian systems like semisolid emulsion products has also been discussed to guide formulation scientists to predict a priori stability of these products.
由于其包含至少两种不混溶液相的复杂微观结构，基于乳剂的局部半固体剂型呈现出高度复杂性，这些相通常具有高粘度。这些复杂的微观结构在热力学上是不稳定的，此类制剂的物理稳定性受配方参数的控制，例如相体积比、乳化剂的类型和浓度、乳化剂的 HLB 值，以及工艺参数，如均化器的速度、时间、温度等。因此，深入了解 DP 中的微观结构以及影响乳剂稳定性的关键因素对于确保基于乳剂的局部半固体产品的质量和保质期至关重要。本综述旨在概述用于稳定半固体产品中包含的药物乳剂的主要策略，以及迄今为止用于评估其长期稳定性的各种表征技术和工具。讨论了使用分析离心机等分散分析仪工具进行加速物理稳定性评估，以预测产品的保质期。此外，还讨论了用于非牛顿体系（如半固体乳剂产品）的相分离速率的数学模型，以指导制剂科学家预测这些产品的预先稳定性。
