Dalby R N, Byron P R
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Pharm Res. 1988 Jan;5(1):36-9. doi: 10.1023/a:1015859311228.
The delivery of particles as small as possible (preferably less than 5 microns) to the respiratory tract should be the aim of those formulating metered dose inhalers (MDIs). This may be facilitated by the formulation of solution, rather than suspension-type, pressurized aerosol units. Two series of MDIs were compared; one contained suspended micronized disodium fluorescein (0.1%, w/v), while the other contained the same concentration of dissolved salicylic acid. Either oleic acid, L-alpha-phosphatidylcholine, or sorbitan trioleate was incorporated at 0.15% (w/v) as suspending agent (disodium fluorescein) or solubilizing agent (salicylic acid). The propellant blend was 70% (w/w) Freon 12 and 30% (w/w) Freon 11 in all cases. This exhibited a vapor pressure of 50.6 psig (444.7 kPa) at 21 degrees C. The output particle size distribution of the aerosol reaching the cascade impactor showed a mass median aerodynamic diameter (MMAD) of approximately 4 and 2 microns for the suspension and solution formulations respectively, regardless of the surfactant used. Larger MMADs were observed for solution aerosols formulated with oleic acid (2.32 microns) compared to those containing L-alpha-phosphatidylcholine (1.93 microns) or sorbitan trioleate (2.07 microns). Possible reasons for these observations are discussed.
将尽可能小的颗粒(最好小于5微米)输送到呼吸道应是那些开发定量吸入器(MDIs)的人员的目标。溶液型而非混悬型的加压气雾剂装置的制剂形式可能有助于实现这一目标。比较了两个系列的MDIs;一个含有混悬的微粉化荧光素二钠(0.1%,w/v),而另一个含有相同浓度的溶解水杨酸。以0.15%(w/v)加入油酸、L-α-磷脂酰胆碱或失水山梨醇三油酸酯作为混悬剂(荧光素二钠)或增溶剂(水杨酸)。在所有情况下,推进剂混合物均为70%(w/w)氟利昂12和30%(w/w)氟利昂11。在21℃时,其蒸气压为50.6 psig(444.7 kPa)。无论使用何种表面活性剂,到达级联冲击器的气雾剂的输出粒径分布显示,混悬剂和溶液剂配方的质量中值空气动力学直径(MMAD)分别约为4微米和2微米。观察到用油酸配制的溶液气雾剂的MMAD(2.32微米)比含有L-α-磷脂酰胆碱(1.93微米)或失水山梨醇三油酸酯(2.07微米)的气雾剂更大。讨论了这些观察结果的可能原因。