Design of experiments approach on the preparation of dry inhaler chitosan composite formulations by supercritical CO2-assisted spray-drying
Design of experiments approach on the preparation of dry inhaler chitosan composite formulations by supercritical CO2-assisted spray-drying
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DOI：
10.1016/j.supflu.2016.04.001
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发表时间：
2016-10-01
影响因子：
3.9
通讯作者：
Aguiar-Ricardo, A.
中科院分区：
文献类型：
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作者：
Cabral, R. P.;Sousa, A. M. L.;Aguiar-Ricardo, A.
肺部递送作为通过干粉吸入将活性成分非侵入性施用至肺部的潜在途径是非常有吸引力的，用于直接靶向肺部或产生全身治疗效果。除了生物相容性、无毒性和生物降解性之外，干粉还必须满足性能递送方面的主要颗粒要求，以便被认为是用于干燥肺部治疗剂的合适载体，例如尺寸、密度和空气动力学性质。这种颗粒的开发通常涉及复杂的优化过程。在这项工作中，实验设计方法（DoE）被用来研究超临界CO2辅助喷雾干燥（SASD）的操作参数的影响，在复合壳聚糖（CHT）微粒的最终性能。研究了CO2与液体流量比（R）、雾化温度和模型药物布洛芬（IBP）的共雾化对颗粒体积直径（D-v，D-50）、跨距、质量中值空气动力学直径（MMAD）、细颗粒分数（FPF）、几何标准偏差（GSD）和排放分数（EF）的影响。使用能够模拟颗粒在肺中沉积的安德森级联撞击器（ACI）设备评估粉末的体外雾化分布。此外，从复合颗粒制剂的体外释放研究进行和建模使用Korsmeyer-Peppas方程，以及溶菌酶生物降解实验。我们能够开发出干燥的壳聚糖复合颗粒，具有合适的特性，可将活性成分输送到肺部。实验设计方法能够在统计学上将操作条件与制剂的最终特征相关联。(C)2016爱思唯尔B. V.保留所有权利。
Pulmonary delivery is very attractive as potential route for non-invasive administration of active ingredients to the lungs, by dry powder inhalation, either for directly target the lungs or render a systemic therapeutic effect. Besides biocompatibility, non-toxicity and biodegradability, dry powders must fulfil main particle requirements in terms of performance delivery in order to be considered suitable carriers for dry pulmonary therapeutics, such as size, density and aerodynamic properties. The development of such particles typically involves a complex process of optimization. In this work a design of experiments approach (DoE) was used to study the effect of supercritical CO2-assisted spray-drying (SASD) operational parameters in the final properties of composite chitosan (CHT) microparticles. The effect of CO2 to liquid flow ratio (R), atomization temperature and the co-atomization of a model active ingredient, ibuprofen (IBP), was studied with respect to the particle volumetric diameter (D-v,D-50), span, mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), geometric standard deviation (GSD) and emitted fraction (EF). The in vitro aerosolization profile of the powders was assessed using an Anderson Cascade Impactor (ACI) equipment able to simulate the deposition of the particles in the lungs. In addition, in vitro release studies from the composite particle formulations were performed and modelled using the Korsmeyer-Peppas equation, as well as lysozyme biodegradation experiments. We were able to develop dry chitosan composite particles with suitable characteristics for the delivery of active ingredients to the lungs. Design of experiments approach was able to statistically correlate the operational conditions with the final characteristics of the formulation. (C) 2016 Elsevier B.V. All rights reserved.