Simple Method to Measure the Aerodynamic Size Distribution of Porous Particles Generated on Lyophilizate for Dry Powder Inhalation

Recently, statistical techniques such as design of experiments are being applied for efficient optimization of oral formulations. To use these statistical techniques for inhalation formulations, efficient methods for rapid determination of the aerodynamic particle size distribution of many samples are needed. Therefore, we aimed to develop a simple method to measure aerodynamic particle size distribution that closely agrees with the results of inhalation characteristic tests. We added attachments for dispersion to the aerodynamic particle sizer (APS) so that formulations could be dispersed under the same condition as for multi-stage liquid impinger (MSLI) measurement. Then, we examined the correlation between MSLI and APS using lyophilizate for dry powder inhalation formulations that generate porous particles just on inhalation. It is difficult to obtain the accurate aerodynamic particle size distribution of porous particles by APS because the particle density is difficult to estimate accurately. However, there was a significant correlation between MSLI and APS when the particle density settings for APS measurement was calculated by a conversion factor based on the result of MSLI. The APS with dispersion attachments and this conversion factor can measure a number of samples in a short time, thereby enabling more efficient optimization of dry powder inhalers.

EVALUATION OF AERODYNAMIC PARTICLE SIZE DISTRIBUTION OF DRUGS USED IN INHALATION THERAPY: A CONCISE REVIEW

Most of the inhalation products in the market use metered dose inhaler (MDI) technology or dry powder inhaler (DPI) technology. MDIs use propellant to deliver desired dose of liquid formulation in aerosol form. DPI contains active in fine particulate form embedded onto an inert carrier. In both cases, amount of drug dispensed from the device reaching the lungs is dependent upon drug product characteristics as well as formulation-device relationship. Hence, in addition to particle size, aerodynamic distribution of the drug upon delivery by the device plays an important role in determining amount of drug reaching the lungs. Therefore particle size characterization is an important tool in determining the extent of drug delivery from the metered dose inhaler. Aerodynamic particle size distribution is frequently determined by use of cascade impactors and data so generated is accepted by regulatory agencies as a tool for predicting efficacy of MDIs and DPIs. This review discusses principle and working of cascade impactors. Additionally, the review also examines the role of laser diffraction technique in estimating size of dispersed particles.