Gupta Abhishek, Stein Stephen W, Myrdal Paul B
College of Pharmacy, University of Arizona, Tucson 85721, USA.
J Aerosol Med. 2003 Summer;16(2):167-74. doi: 10.1089/089426803321919924.
The effects of formulation parameters on the product performance characteristics of solution metered dose inhalers (MDIs) were determined using ethanol as the cosolvent and HFA 134a as the propellant. Solubility of beclomethasone dipropionate (BDP) was determined in various blends of 134a and ethanol and was shown to increase with ethanol concentration. Product performance was assessed using the APS Model 3306 Impactor Inlet in conjunction with APS Model 3320 Aerodynamic Particle Sizer (APS). Nine solution formulations containing various BDP and ethanol concentrations were studied. Chemical analysis of the Impactor Inlet was performed in order to determine the "respirable" deposition of the MDI system. With increased ethanol concentration, the throat deposition and plate deposition increased and the respirable deposition decreased. The mass median aerodynamic diameter (MMAD) increased with the increasing drug concentration, but did not show a significant increase with an increase in ethanol concentration. This indicates that the efficiency of solution MDIs decreases with increased ethanol concentration. A Maximum Respirable Mass (MRM) was calculated based on the drug solubility at a particular ethanol concentration and the respirable deposition for a 50mcl valve and QVAR actuator for that ethanol concentration. The MRM represents the maximum amount of a given drug that can be delivered to the lungs theoretically and is very sensitive to the solubility profile of the drug. The MRM increased with the increasing ethanol concentration in the formulation until a plateau was reached at an ethanol concentration of 10-15% w/w. The MRM initially increases with increase in ethanol concentration due to the increase in drug solubility. However, at higher ethanol concentrations the increase in drug solubility was negated by a decrease in the respirable deposition. This study illustrates the importance of considering both formulation properties and product performance characteristics when optimizing a metered dose inhaler drug delivery system.
以乙醇作为助溶剂、HFA 134a作为抛射剂，测定了制剂参数对溶液型定量吸入器（MDIs）产品性能特征的影响。测定了丙酸倍氯米松（BDP）在134a和乙醇的各种混合溶剂中的溶解度，结果表明其溶解度随乙醇浓度的增加而升高。使用APS 3306型撞击器入口与APS 3320型空气动力学粒径分析仪（APS）结合来评估产品性能。研究了九种含有不同BDP和乙醇浓度的溶液制剂。对撞击器入口进行化学分析，以确定MDI系统的“可吸入”沉积量。随着乙醇浓度的增加，咽部沉积和平板沉积增加，可吸入沉积减少。质量中值空气动力学直径（MMAD）随药物浓度的增加而增大，但未显示出随乙醇浓度的增加而显著增大。这表明溶液型MDIs的效率随乙醇浓度的增加而降低。根据特定乙醇浓度下的药物溶解度以及该乙醇浓度下50微升阀门和QVAR促动器的可吸入沉积量，计算出最大可吸入质量（MRM）。MRM代表理论上可输送到肺部的给定药物的最大量，并且对药物的溶解度曲线非常敏感。制剂中MRM随乙醇浓度的增加而升高，直到乙醇浓度达到10 - 15% w/w时达到平稳状态。MRM最初随乙醇浓度的增加而升高是由于药物溶解度的增加。然而，在较高乙醇浓度下，药物溶解度的增加被可吸入沉积量的减少所抵消。本研究说明了在优化定量吸入器药物递送系统时，考虑制剂性质和产品性能特征两者的重要性。
