Abstract
Introducing a new approach for dry powder inhaler characterization aids understanding of the dispersion of the formulation during device actuation. In this note we show how the Morphologi automated imaging system can be used to understand the degree of powder dispersion achieved during the operation of a dry powder inhaler by analyzing powder fractions collected using cascade impaction.
Introduction
During research and development of orally inhaled and nasal drug products (OINDPs) Next Generation Impactors (NGIs) are well accepted and routinely used as a method to assess the aerodynamic particle size distribution of the drug in a formulation. This technique is described in both the European1 and United States Pharmacopeia2, which specify test methods for use with Dry Powder Inhalation (DPI) formulations. In general, it is accepted for DPI formulations that, to specifically target drug delivery to the lungs, the particles should be in the 1 to 5 micron size range. The aerodynamic size of particles expected to be collected at each stage of an NGI is calculated according to the flow rate of actuation as described in the Pharmacopeia. An important advantage of the NGI as a particle sizer over other techniques is that, as well as classifying particles according to their aerodynamic particle size, it allows the chemical specificity of the particles to be determined via High Pressure Liquid Chromatography (HPLC). Thus, the fraction of active pharmaceutical ingredient (API) of the appropriate size to reach the target site can be assessed. However, the disadvantage of this method is that HPLC analysis requires the dissolution of collected particles, which means that all information about the physical properties of the particles at each stage is lost.It is also of interest to gain a better understanding of the physical properties of a material, especially whether particles delivered to the lower stages of the impactor are agglomerated or well dispersed primary particles. Characterization of particles collected on each stage of an impactor by automated image analysis allows the particle size and shape to be assessed in a quantitative manner and allows the particles and agglomerate structures to be visualized.3 Another benefit in combining the techniques of NGI particle classification with image analysis is that the classification of a powder into narrow size classes by the NGI ensures the material on each stage is within the size range for measurement using a single microscope objective (ie. Magnification). Therefore, concerns relating to the dynamic range for image analysis measurements are addressed.Aims and Objectives
The aims of the study were two fold:- to compare the theoretical aerodynamic particle size of particles collected on the various stages of an NGI with the two dimensional particles size measured by image analysis,
- to ascertain whether any trends in particle shape are observed by visualizing the particles collected on each stage of the NGI.
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