School of Pharmacy and Pharmaceutical Sciences, Panoz Insitute, Trinity College Dublin, Dublin 2, Ireland.
JDP Pharma Consulting, LLC, PO Box 1127, San Carlos, CA, United States.
Int J Pharm. 2019 May 1;562:228-240. doi: 10.1016/j.ijpharm.2019.03.004. Epub 2019 Mar 5.
The present study evaluates the effect of L-leucine concentration and operating parameters of a laboratory spray dryer on characteristics of trehalose dry powders, with the goal of optimizing production of these powders for inhaled drug delivery. Trehalose/L-leucine mixtures were spray dried from aqueous solution using a laboratory spray dryer. A factorial design of experiment (DoE) was undertaken and process parameters adjusted were: inlet temperature, gas flow rate, feed solution flow rate (pump setting), aspiration setting and L-leucine concentration. Resulting powders were characterised in terms of particle size, yield, residual moisture content, and glass transition temperature. Particle size was mainly influenced by gas flow rate, whereas product yield and residual moisture content were found to be primarily affected by inlet temperature and spray solution feed rate respectively. Interactions between a number of different process parameters were elucidated, as were relationships between different responses. The leucine mass ratio influenced the physical stability of powders against environmental humidity, and a high leucine concentration (30% w/w) protected amorphous trehalose from moisture induced crystallization. High weight ratio of leucine in the formulation, however, negatively impacted the aerosol performance. Thus, in terms of L-leucine inclusion in a formulation designed for pulmonary delivery, a balance needs to be found between physical stability and deposition characteristics.
本研究评估了 L-亮氨酸浓度和实验室喷雾干燥机操作参数对海藻糖干粉特性的影响，旨在优化用于吸入式药物输送的这些粉末的生产。海藻糖/L-亮氨酸混合物从水溶液中用实验室喷雾干燥机喷雾干燥。采用析因设计实验（DoE），并调整了工艺参数：入口温度、气体流速、进料溶液流速（泵设置）、抽吸设置和 L-亮氨酸浓度。所得粉末的特性为粒径、产率、残余水分含量和玻璃化转变温度。粒径主要受气体流速影响，而产品产率和残余水分含量主要受入口温度和喷雾溶液进料速率的影响。阐明了许多不同工艺参数之间的相互作用，以及不同响应之间的关系。亮氨酸的质量比对粉末对环境湿度的物理稳定性有影响，高浓度亮氨酸（30%w/w）保护无定形海藻糖免受水分诱导的结晶。然而，制剂中亮氨酸的高重量比会对气溶胶性能产生负面影响。因此，就用于肺部输送的制剂中包含亮氨酸而言，需要在物理稳定性和沉积特性之间找到平衡。
