Systematic Evaluation of the Effect of Formulation Variables on In Vitro Performance of Mometasone Furoate Suspension-Metered Dose Inhalers.
Systematic Evaluation of the Effect of Formulation Variables on In Vitro Performance of Mometasone Furoate Suspension-Metered Dose Inhalers.
复制标题
DOI：
10.1208/s12248-021-00638-1
复制
发表时间：
2021-12-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
定量吸入器（MDI）在肺部疾病中的治疗获益主要取决于气雾剂性能，而气雾剂性能取决于制剂变量（药物和辅料）、器械设计和患者相互作用。本研究提供了一项全面的调查，以更好地了解处方变量对糠酸莫米松（MF）混悬剂MDI产品性能的影响。研究了MF粒度（体积中位直径; X50）和辅料浓度（分别为乙醇和油酸、助溶剂和表面活性剂）对选定关键质量属性（递送剂量（DD）、小于5 μm的微粒剂量（FPD < 5）、喉外剂量和中位溶出时间（MDT））的影响。根据简化析因实验设计（DOE）方法生产了8种MF-MDI制剂（每批1种），其中包括不同X50（1.1和2 μm）、乙醇浓度（0.45、0.9、1.8和3.6%w/w）和油酸浓度（0.001和0.025%w/w）的相关制剂水平。这些MF-MDI制剂的体外评价表明药物颗粒的X50、油酸和乙醇罐浓度作为控制MF混悬液基MDI产品性能的关键制剂变量的重要性。随后利用这些制剂变量对DD、FPD < 5、喉外剂量和MDT的影响来开发将制剂因素与对体外性能测量的影响联系起来的经验关系。所开发的策略可能是有用的预测MF-MDI产品的性能在MDI产品的开发和制造。本研究中使用的系统DOE方法可为了解控制MF-MDI产品性能的配方变量提供见解。
The therapeutic benefits of metered dose inhalers (MDIs) in pulmonary disorders are mainly driven by aerosol performance, which depends on formulation variables (drug and excipients), device design, and patient interactions. The present study provides a comprehensive investigation to better understand the effect of formulation variables on mometasone furoate (MF) suspension-based MDI product performance. The effects of MF particle size (volume median diameter; X50) and excipient concentration (ethanol and oleic acid, cosolvent, and surfactant, respectively) on selected critical quality attributes (delivered dose (DD), fine particle dose of particles lesser than 5 μm (FPD < 5), ex-throat dose and median dissolution time (MDT)) were studied. Eight MF-MDI formulations (one per batch) were manufactured based on a reduced factorial design of experiment (DOE) approach, which included relevant formulation levels with varying X50 (1.1 and 2 μm), concentration of ethanol (0.45, 0.9, 1.8, and 3.6%w/w), and oleic acid (0.001 and 0.025%w/w). The in vitro evaluation of these MF-MDI formulations indicated the importance of drug particle’s X50, oleic acid, and ethanol canister concentration as critical formulation variables governing the performance of MF suspension-based MDI products. The effect of these formulation variables on DD, FPD < 5, ex-throat dose, and MDT was subsequently utilized to develop empirical relationships linking formulation factors with effects on in vitro performance measures. The developed strategy could be useful for predicting MF-MDI product performance during MDI product development and manufacturing. The systematic DOE approach utilized in this study may provide insights into the understanding of the formulation variables governing the MF-MDI product performance.
登录
查看更多内容
DOI：
10.1089/jamp.2012.0986
发表时间：
2013-12-01
影响因子：
3.4
作者：
Olsson, Bo;Borgstrom, Lars;Svensson, Marten
通讯作者：
Svensson, Marten
影响因子：
3.3
作者：
Kaviratna, Anubhav;Tian, Geng;Guo, Changning
通讯作者：
Guo, Changning
影响因子：
2.9
作者：
Hochhaus, G;Mollmann, H;GonzalezRothi, RJ
通讯作者：
GonzalezRothi, RJ
影响因子：
3.3
作者：
Schroeter, Jeffry D.;Sheth, Poonam;Saluja, Bhawana
通讯作者：
Saluja, Bhawana
影响因子：
4.7
作者：
Gernaey, Krist V.;Gani, Rafiqul
通讯作者：
Gani, Rafiqul