Enhanced control of particle size with microfluidization and membrane microfiltration

C Moura, J Santos, F Gaspar

Background: Particle size (PS) and particle size distribution (PSD) are two of the most important attributes when designing an inhalation drug product. A fine control of both these parameters is not easily achieved by current available technologies. The new method herein presented consists in combining a microfluidization step with a cross-flow microfiltration step. The combination of these technologies allows the production of particles with stricter limits in terms of size and distribution and therefore enables a more efficient delivery to the lung.
Methods: A microfluidizer and two hydrophilic flat sheet track-etched polycarbonate membranes (30 and 20 μm pore sizes) were used. The permeability critical flux (Jvcrit) and critical transmembrane pressure (TMPcrit) were determined. Filtration tests were conducted below the Jvcrit, using, as model system, a 5% (w/w) aqueous suspension of fluticasone propionate. The effects of the addition of surfactant and ultrasound were also assessed. PS and PSD of the particles in the feed and permeate were monitored by focused beam reflectance measurement (FBRM). Laser diffraction was also used for comparison purposes.
Results: The proof of concept work shows that the selected membranes are capable of efficiently classifying the feed suspension according to membrane pore size, narrowing the PSD of permeates.
Conclusions: The combination of these two technologies – microfluidization and cross-flow microfiltration – provides a greater control of PS and PSD and, therefore, it is expected to result in particles with enhanced performance for inhalation delivery.

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