The application of 'in-flight' laser diffraction to the particle size characterization of a model suspension metered dose inhaler.

摘要

Laser diffraction (LD) has been used to measure the particle size of pharmaceutical aerosols. In this study, the application of LD for measuring the particle size of a model suspension metered dose inhaler (MDI) containing a hydrofluorocarbon propellant was investigated using a Sympatec LD apparatus with an automatic spray device. In order to obtain meaningful results, test parameters such as spray distance and temperature needed to be optimized for this model formulation and then well-controlled during testing. Using a suitable LD test methodology, it was found that particle size variations as a function of nonvolatile excipient levels as well as changes to the suspended drug substance could be observed and, in some cases, correlated to cascade impaction results. Based on these studies, it is believed that the methodology is a valuable rapid screening tool for investigating variations in or permutations to suspension MDI formulations. Nonetheless, the trends in the LD droplet size are complicated by the presence of drug-free droplets. Consequently, the results are not always consistent with other particle sizing techniques such as cascade impaction in which the droplets associated with drug are evaluated. Therefore, for suspension MDIs, the "in-flight" LD method would probably best be utilized as a complementary sizing technique during formulation development.