Tiwari D, Goldman D, Malick W A, Madan P L
College of Pharmacy, St. John's University, Jamaica, New York 11439, USA.
Pharm Dev Technol. 1998 May;3(2):163-74. doi: 10.3109/10837459809028492.
This study was undertaken to evaluate tetrafluoroethane (P134a) as a possible chlorofluorocarbon (CFC) replacement for albuterol metered dose inhaler (MDI) formulations. Preformulation studies using three conventional (oleic acid, sorbitan trioleate, lecithin) and a nonconventional (oleyl alcohol) surfactant indicated that P134a is a poor solvent for these surfactants. A slight improvement in the solubility of oleic acid and oleyl alcohol was observed by the addition of low concentrations of a nonconventional cosolvent diethyl ether (< or = 0.5% w/w). Formulation screening of the prepared albuterol formulations indicated that suspensions containing oleyl alcohol and diethyl ether had a slower rate of separation. Product performance of four albuterol formulations containing oleyl alcohol, diethyl ether, and P134a was evaluated and compared to a leading commercial formulation containing CFC propellants (Ventolin). Ventolin showed excellent agreement between the emitted dose and the expected dose but only a reasonable agreement was observed with one of the better P134a-containing formulations. P134a formulations showed higher internal pressure in comparison to the CFC formulation. The concentrations of the surfactant, drug, and cosolvent appeared to have a significant impact on the uniformity of the emitted dose. Determination of particle size using the time-of-flight and the laser diffraction analyzer revealed that P134a formulations had equal or smaller particle size than the formulation containing CFC. However, the CFC formulation showed a higher respirable fraction than the P134a formulation when measured by the two inertial impaction methods. The observed particle size distribution of the formulation appeared to depend on the measuring method used.
本研究旨在评估四氟乙烷（P134a）作为沙丁胺醇定量吸入气雾剂（MDI）制剂中氯氟烃（CFC）的一种可能替代品。使用三种常规表面活性剂（油酸、失水山梨醇三油酸酯、卵磷脂）和一种非常规表面活性剂（油醇）进行的处方前研究表明，P134a对这些表面活性剂而言是一种不良溶剂。通过添加低浓度的非常规共溶剂乙醚（≤0.5% w/w），观察到油酸和油醇的溶解度略有提高。对所制备的沙丁胺醇制剂进行的处方筛选表明，含有油醇和乙醚的混悬液的分离速率较慢。对四种含有油醇、乙醚和P134a的沙丁胺醇制剂的产品性能进行了评估，并与一种含CFC推进剂的领先商业制剂（万托林）进行了比较。万托林在喷出剂量和预期剂量之间显示出极好的一致性，但在一种较好的含P134a制剂中仅观察到合理的一致性。与CFC制剂相比，P134a制剂显示出更高的内部压力。表面活性剂、药物和共溶剂的浓度似乎对喷出剂量的均匀性有显著影响。使用飞行时间和激光衍射分析仪测定粒径表明，P134a制剂的粒径等于或小于含CFC的制剂。然而，当通过两种惯性撞击法测量时，CFC制剂的可吸入部分比P134a制剂更高。所观察到的制剂粒径分布似乎取决于所使用的测量方法。
