Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols.
Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols.
复制标题
数值模型以表征组合药物和吸湿性纳米粒子气溶胶的大小增加。
DOI：
10.1080/02786826.2011.566592
复制
发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Hindle M
中科院分区：
文献类型：
--
作者：
Longest PW;Hindle M
增强赋形剂生长是一种新提出的呼吸递送策略，其中将由药物和吸湿性赋形剂组成的亚微米或纳米颗粒递送至气道，以最大限度地减少胸外沉积损失并最大限度地增加肺滞留。本研究的目的是开发一种经验证的吸湿性辅料和辅料-药物颗粒组合的气溶胶尺寸增加的数学模型，并将该模型应用于表征典型呼吸条件下的生长。与体外实验相比，液滴生长模型准确地预测了单一组分和组合药物和赋形剂颗粒的尺寸增加。对于典型的呼吸道给药条件，该模型表明，液滴尺寸的增加可以有效地与新定义的吸湿参数和颗粒中药物和赋形剂的初始体积分数的乘积相关。然后开发了一系列生长相关性，依次包括初始药物和赋形剂质量负载，初始气溶胶大小和气溶胶数浓度的影响。考虑到EEG递送，对于与吸湿性和非吸湿性药物组合的一系列吸湿性赋形剂，观察到大的直径增长率（2.1-4.6）。这些直径增长率是在50%及以下的赋形剂质量负载和实际气溶胶数浓度下实现的。然后将所开发的相关性用于指定工程化胰岛素纳米颗粒的适当初始质量负载，以实现预定的尺寸增加，同时最大化药物有效负载并最小化吸湿性赋形剂的量。
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.
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影响因子：
4.5
作者：
Longest, P. Worth;Hindle, Michael
通讯作者：
Hindle, Michael
影响因子：
4.5
作者：
FINLAY, WH;STAPLETON, KW
通讯作者：
STAPLETON, KW
DOI：
10.1089/jamp.2008.0708
发表时间：
2009-06-01
影响因子：
3.4
作者：
Longest, P. Worth;Hindle, Michael
通讯作者：
Hindle, Michael
影响因子：
5.2
作者：
Asgharian, B;Hofman, W;Bergmann, R
通讯作者：
Bergmann, R
DOI：
10.1080/02786821003749525
发表时间：
2010-06-01
期刊：
Aerosol science and technology : the journal of the American Association for Aerosol Research
影响因子：
--
作者：
Longest PW;McLeskey JT Jr;Hindle M
通讯作者：
Hindle M