Longest P Worth, Hindle Michael
Department of Mechanical Engineering, Virginia Commonwealth University, Richmond, VA.
Aerosol Sci Technol. 2011 Jan 1;45(7):884-899. doi: 10.1080/02786826.2011.566592.
Enhanced excipient growth is a newly proposed respiratory delivery strategy in which submicrometer or nanometer particles composed of a drug and hygroscopic excipient are delivered to the airways in order to minimize extrathoracic depositional losses and maximize lung retention. The objective of this study was to develop a validated mathematical model of aerosol size increase for hygroscopic excipients and combination excipient-drug particles and to apply this model to characterize growth under typical respiratory conditions. Compared with in vitro experiments, the droplet growth model accurately predicted the size increase of single component and combination drug and excipient particles. For typical respiratory drug delivery conditions, the model showed that droplet size increase could be effectively correlated with the product of a newly defined hygroscopic parameter and initial volume fractions of the drug and excipient in the particle. A series of growth correlations was then developed that successively included the effects of initial drug and excipient mass loadings, initial aerosol size, and aerosol number concentration. Considering EEG delivery, large diameter growth ratios (2.1-4.6) were observed for a range of hygroscopic excipients combined with both hygroscopic and non-hygroscopic drugs. These diameter growth ratios were achieved at excipient mass loadings of 50% and below and at realistic aerosol number concentrations. The developed correlations were then used for specifying the appropriate initial mass loadings of engineered insulin nanoparticles in order to achieve a predetermined size increase while maximizing drug payload and minimizing the amount of hygroscopic excipient.
增强型辅料生长是一种新提出的呼吸道给药策略，即由药物和吸湿性辅料组成的亚微米或纳米颗粒被输送到气道，以尽量减少胸外沉积损失并最大化肺部滞留。本研究的目的是建立一个经过验证的数学模型，用于描述吸湿性辅料以及辅料 - 药物组合颗粒的气溶胶粒径增长，并应用该模型来表征典型呼吸条件下的颗粒生长情况。与体外实验相比，液滴生长模型准确预测了单一组分以及药物与辅料组合颗粒的粒径增长。对于典型的呼吸道药物递送条件，该模型表明液滴粒径增长可以与新定义的吸湿性参数以及颗粒中药物和辅料的初始体积分数的乘积有效关联。随后建立了一系列生长相关性，依次纳入了初始药物和辅料质量负载、初始气溶胶粒径和气溶胶数浓度的影响。考虑到增强型辅料生长给药，观察到一系列吸湿性辅料与吸湿性和非吸湿性药物组合时的大直径生长比（2.1 - 4.6）。这些直径生长比在辅料质量负载为50%及以下且气溶胶数浓度符合实际情况时实现。然后，所建立的相关性被用于确定工程化胰岛素纳米颗粒的合适初始质量负载，以便在最大化药物载量并最小化吸湿性辅料用量的同时实现预定的粒径增长。
