MDRS assesses not only the amount of API in each sample but also the extent of agglomeration of the API as a function of particle size, and whether any agglomeration is between API particles and the carrier or between API particles and other API particles. In this way MDRS provides greater insight into the de-agglomeration and dispersion processes that are taking place, or indeed failing to occur, during dose delivery. This resulting data support the more knowledgeable manipulation of powder properties, helping formulators to reach drug delivery targets more quickly. They can also be useful in the demonstration of bioequivalence.
Rapid data acquisition
Laser diffraction particle sizing systems are fully automated and acquire data at rates of up to 10,000 PSD measurements per second. In addition, because these systems measure over a size range of around 100 nm to >1 mm, both agglomerated and fully dispersed particles can be measured simultaneously during device actuation.
The rapidity of laser diffraction enables tracking of the evolution of particle size and changes in aerosol concentration in real time during a DPI actuation. This makes it possible to assess, for example, if the dose is progressively released from the device or whether it is emitted over a very short timescale at much higher concentrations. Equally importantly, laser diffraction can be used to investigate dose dispersion over a far wider range of flow rates than is accessible using cascade impaction. This allows researchers to assess whether dose delivery is flow rate dependent or not, to fully scope performance at relatively low or high flow rates to mimic the physiology of different patient groups and, in the case of generic development, to more robustly demonstrate bioequivalence.
Because of its speed, laser diffraction analysis adds the ability to step through different sets of experimental conditions much more quickly than with cascade impaction, supporting efficient delivery of the broader experimentation associated with Quality by Design. It allows developers to rapidly scope the impact of changing formulation and device parameters, providing a greater understanding of how the formulation is released from the OINDP and how to direct aerosolization to a state of more complete dispersion.
