Khattak Muhammad Ijaz Khan, Ahmed Naveed, Umer Muhammad Farooq, Riaz Amina, Ahmad Nasir Mehmood, Khan Gul Majid
Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Department of Pharmacy, University of Swabi, Anbar, Swabi 23561, KPK, Pakistan.
Pharmaceutics. 2020 Nov 9;12(11):1065. doi: 10.3390/pharmaceutics12111065.
Intricate formulation methods and/or the use of sophisticated equipment limit the prevalence of liposomal dosage-forms. Simple techniques are developed to assemble amphiphiles into globular lamellae while transiting from the immiscible organic to the aqueous phase. Various parameters are optimized by injecting chloroform solution of amphiphiles into the aqueous phase and subsequent removal of the organic phase. Further simplification is achieved by reorienting amphiphiles through a spontaneous phase transition in a swirling biphasic system during evaporation of the organic phase under vacuum. Although the chloroform injection yields smaller Z-average and poly-dispersity-index the spontaneous phase transition method overrides simplicity and productivity. The increasing solid/solvent ratios results in higher Z-average and broader poly-dispersity-index of liposomes under a given set of experimental conditions, and vice versa. Surface charge dependent large unilamellar vesicles with a narrow distribution have poly-dispersity-index < 0.4 in 10 μM saline. As small and monodisperse liposomes are prerequisites in targeted drug delivery strategies, hence the desired Z-average < 200 d.nm and poly-dispersity-index < 0.15 is obtained through the serial membrane-filtration method. Phosphatidylcholine/water 4 μmol/mL is achieved at a temperature of 10°C below the phase-transition temperature of phospholipids, ensuring suitability for thermolabile entities and high entrapment efficiency. Both methods furnish the de-novo rearrangement of amphiphiles into globular lamellae, aiding in the larger entrapped volume. The immiscible organic phase benefits from its faster and complete removal from the final product. High cholesterol content (55.6 mol%) imparts stability in primary hydration medium at 5 ± 3 °C for 6 months in light-protected type-1 glass vials. Collectively, the reported methods are novel, scalable and time-efficient, yielding high productivity in simple equipment.
复杂的制剂方法和/或先进设备的使用限制了脂质体剂型的普及。人们开发了简单的技术，以便在从互不相溶的有机相转变为水相的过程中，将两亲分子组装成球状片层。通过将两亲分子的氯仿溶液注入水相并随后去除有机相，对各种参数进行了优化。在真空下有机相蒸发过程中，通过在旋转双相系统中自发的相变来重新定向两亲分子，实现了进一步简化。尽管氯仿注入法得到的Z平均粒径和多分散指数较小，但自发相变法在简便性和生产率方面更具优势。在给定的一组实验条件下，固体/溶剂比的增加会导致脂质体的Z平均粒径增大和多分散指数变宽，反之亦然。在10 μM盐溶液中，具有窄分布的表面电荷依赖性大单层囊泡的多分散指数<0.4。由于小且单分散的脂质体是靶向给药策略的前提条件，因此通过连续膜过滤法可获得所需的Z平均粒径<200 d.nm和多分散指数<0.15。在低于磷脂相变温度10°C的温度下可实现4 μmol/mL的磷脂酰胆碱/水，确保适用于热不稳定物质并具有高包封效率。两种方法都能使两亲分子重新排列形成球状片层，有助于增大包封体积。互不相溶的有机相有利于从最终产品中更快、更完全地去除。高胆固醇含量（55.6 mol%）可在5±3°C的一级水合介质中，在避光的1型玻璃瓶中保持6个月的稳定性。总体而言，所报道的方法新颖、可扩展且省时，在简单设备中具有高生产率。
