Real-time particle size analysis using focused beam reflectance measurement as a process analytical technology tool for continuous microencapsulation process

Muhaimin Muhaimin,Anis Yohana Chaerunisaa,Roland Bodmeier

doi:10.1038/s41598-021-98984-9

Muhaimin Muhaimin, Anis Yohana Chaerunisaa + Show 1 more

Open Access

https://doi.org/10.1038/s41598-021-98984-9

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Abstract

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM). In this paper, we use FBRM measurements to investigate the effects of polymer type and compare the size distributions to those obtained using other sizing methods such as optical microscope and laser diffraction. FBRM was also utilized to measure the length-weighted chord length distribution (CLD) and particle size distribution (PSD) online during particle solidification, which could not be done with laser diffraction or nested sieve analysis. The chord lengths and CLD data were taken at specific times using an online FBRM probe mounted below the microparticle. The timing of the FBRM determinations was coordinated with the selection of microparticle samples for particle size analysis by optical microscope and laser diffraction calculation as a reference. For all three produced batches tested, FBRM, laser diffraction, and sieve analysis yielded similar results. Hardening time for the transformation of emulsion droplets into solid microparticles occurred within the first 10.5, 19, 25, 30, and 55 min, according to FBRM results. The FBRM CLDs revealed that a larger particle size mean resulted in a longer CLD and a lower peak of particle number. The FBRM data revealed that the polymer type had a significant impact on microparticle CLD and the transformation process.

Highlights

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM)
FBRM measurement on particle size relatively compared to those obtained using an optical microscope and laser diffraction revealed that there were no variations in particle size of microcapsules (Table 1)
Three batches of microparticles having different sizes were measured with the different equipments to which Focused Beam Reflectance Measurements (FBRM), laser diffraction (LD) and sieve analysis

Summary

Introduction

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM). According to Mehta et al, solubilities of polymers in organic solvents determine the solidification rate of the polymers during the microparticle preparation process, which in turn affects microparticle properties such as particle s ize[13]. The hardening speed of microparticles in the solvent evaporation cycle is affected by the solubility of the polymer in organic solvents, which impact on microparticle properties such as particle size, volume of encapsulated drugs, matrix porosity, solvent residues, and initial drug release[16,17,18,19]. The Focused Beam Reflectance Method (FBRM) technique allows for in-situ measurements to monitor particle/droplet size in real time during the microencapsulation process[23,24,25,26]. This device can visually track the transformation of emulsion droplets into stable microparticles, known as hardening time

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