Shah Parinbhai, Goodyear Benjamin, Haq Anika, Puri Vinam, Michniak-Kohn Bozena
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA.
Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Pharmaceutics. 2020 Mar 9;12(3):246. doi: 10.3390/pharmaceutics12030246.
Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery system that may be used to deliver desoximetasone via topical product application in order to mitigate common side effects associated with traditional oral delivery routes. The aim of this research was to identify the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of drug-loaded niosomes using a systematic quality by design (QbD) approach. An organic phase injection method was developed and used to manufacture the niosomes. The CMAs were identified to be drug amount, concentrations of surfactant and cholesterol, and types of lipids. The CPPs were phase volumes, temperature, mixing parameters, and addition rate based on previous research. The quality attributes measured were entrapment efficiency, particle size distribution, PDI, and zeta potential. These were used to determine the quality target product profile (QTPP) of niosomes. The experimental data indicate that the critical impacting variables for niosomes are: surfactant and cholesterol concentrations, mixing parameters, and organic-phase addition rate. Based on the experimental results of this study methanol:diethyl ether (75:25) as the organic system, drug:surfactant:cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate is the ideal combination to achieve desirable desoximetasone niosomes with optimum entrapment efficiency and particle size for topical application.
外用皮质类固醇用于治疗多种皮肤疾病，如过敏反应、湿疹和牛皮癣。脂质体是一种新型的基于表面活性剂的给药系统，可通过局部应用产品来递送地索奈德，以减轻与传统口服给药途径相关的常见副作用。本研究的目的是使用系统的质量源于设计（QbD）方法，确定影响载药脂质体关键特性的关键物料属性（CMA）和关键工艺参数（CPP）。开发了一种有机相注射法并用于制备脂质体。确定的CMA为药物用量、表面活性剂和胆固醇浓度以及脂质类型。根据先前的研究，CPP为相体积、温度、混合参数和添加速率。所测量的质量属性为包封率、粒径分布、PDI和zeta电位。这些用于确定脂质体的质量目标产品概况（QTPP）。实验数据表明，脂质体的关键影响变量为：表面活性剂和胆固醇浓度、混合参数以及有机相添加速率。基于本研究的实验结果，甲醇：乙醚（75:25）作为有机体系，药物：表面活性剂：胆固醇浓度为1:2:1，硬脂酸作为电荷诱导材料，外相体积20 mL和内相体积10 mL，外相温度65°C，混合时间60分钟，混合速度650 RPM以及添加速率1 mL/ml是实现具有最佳包封率和粒径的理想地索奈德脂质体用于局部应用的理想组合。
