Determination of the Porosity of PLGA Microparticles by Tracking Their Sedimentation Velocity Using a Flow Imaging Microscope (FlowCAM)

A S Sediq,W Jiskoot,M R Nejadnik,S K D Waasdorp,R Verrijk,J Meulenaar,M M C Van Beers

doi:10.1007/s11095-017-2120-8

Abstract

PurposeTo investigate whether particle sedimentation velocity tracking using a flow imaging microscope (FlowCAM) can be used to determine microparticle porosity.MethodsTwo different methods were explored. In the first method the sedimentation rate of microparticles was tracked in suspending media with different densities. The porosity was calculated from the average apparent density of the particles derived by inter- or extrapolation to the density of a suspending medium in which the sedimentation velocity was zero. In the second method, the microparticle size and sedimentation velocity in one suspending fluid were used to calculate the density and porosity of individual particles by using the Stokes’ law of sedimentation.ResultsPolystyrene beads of different sizes were used for the development, optimization and validation of the methods. For both methods we found porosity values that were in excellent agreement with the expected values. Both methods were applied to determine the porosity of three PLGA microparticle batches with different porosities (between about 4 and 52%). With both methods we obtained microparticle porosity values similar to those obtained by mercury intrusion porosimetry.ConclusionsWe developed two methods to determine average microparticle density and porosity by sedimentation velocity tracking, using only a few milligrams of powder.

Highlights

Formulating active pharmaceutical ingredients (API) in controlled release systems is a potent strategy to maintain drug levels for prolonged periods within the therapeutic window, which may increase the efficiency of therapy, reduce the costs and improve patient compliance and comfort [1]
Considering the developments in flow imaging instruments with respect to image quality, sizing precision and accuracy [10] and their increasingly widespread use in pharmaceutical laboratories, we have evaluated sedimentation velocity tracking using a flow imaging microscope (FlowCAM) for measuring the density and porosity of poly lactic-co-glycolic acid (PLGA) microparticles
We present two methods using a FlowCAM to determine the porosity of PLGA microparticles

Summary

Introduction

Formulating active pharmaceutical ingredients (API) in controlled release systems is a potent strategy to maintain drug levels for prolonged periods within the therapeutic window, which may increase the efficiency of therapy, reduce the costs and improve patient compliance and comfort [1] Owing to their long clinical experience and favorable performance in terms of biodegradability and biocompatibility, PLGA microparticles fulfill the needs for controlled release in the area of parenteral pharmaceutical formulations, with a number of FDA approved drug products on the market today [2]. Mercury porosimetry has the advantage of having certified reference material and standard measurement protocols [7] Each of these methods has a number of major drawbacks. Fully automated equipment is commercially available for both methods, such equipment is expensive and not available in many pharmaceutical laboratories

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