Optimising poly(lactic-co-glycolic acid) microparticle fabrication using a Taguchi orthogonal array design-of-experiment approach

R A Mensah; S B Kirton; M T Cook; I D Styliari; V Hutter; D Y S Chau

doi:10.1371/journal.pone.0222858

Optimising poly(lactic-co-glycolic acid) microparticle fabrication using a Taguchi orthogonal array design-of-experiment approach

PLoS One. 2019 Sep 26;14(9):e0222858. doi: 10.1371/journal.pone.0222858. eCollection 2019.

Authors

R A Mensah^{1

2}, S B Kirton¹, M T Cook¹, I D Styliari¹, V Hutter¹, D Y S Chau^{1

2}

Affiliations

¹ Department of Clinical and Pharmaceutical Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, England, United Kingdom.
² Department of Biomaterials and Tissue Engineering, Eastman Dental Institute, UCL, London, England, United Kingdom.

Abstract

The objective of this study was to identify, understand and generate a Taguchi orthogonal array model for the formation of 10-50 μm microparticles with applications in topical/ocular controlled drug delivery. Poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated by the single emulsion oil-in-water method and the particle size was characterized using laser diffraction and scanning electronic microscopy (SEM). Sequential Taguchi L12 and L18 orthogonal array (OA) designs were employed to study the influence of ten and eight parameters, respectively, on microparticle size (response). The first optimization step using the L12 design showed that all parameters significantly influenced the particle size of the prepared PLGA microparticles with exception of the concentration of poly(vinyl alcohol) (PVA) in the hardening bath. The smallest mean particle size obtained from the L12 design was 54.39 μm. A subsequent L18 design showed that the molecular weight of PLGA does not significantly affect the particle size. An experimental run comprising of defined parameters including molecular weight of PLGA (89 kDa), concentration of PLGA (20% w/v), concentration of PVA in the emulsion (0.8% w/v), solvent type (ethyl acetate), organic/aqeuous phase ratio (1:1 v/v), vortexing speed (9), vortexing duration (60 seconds), concentration of PVA in hardening bath (0.8% w/v), stirring speed of hardening bath (1200 rpm) and solvent evaporation duration (24 hours) resulted in the lowest mean particle size of 23.51 μm which was predicted and confirmed by the L18 array. A comparable size was demonstrated during the fabrication of BSA-incorporated microparticles. Taguchi OA design proved to be a valuable tool in determining the combination of process parameters that can provide the optimal condition for microparticle formulation. Taguchi OA design can be used to correctly predict the size of microparticles fabricated by the single emulsion process and can therefore, ultimately, save time and costs during the manufacturing process of drug delivery formulations by minimising experimental runs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemistry, Pharmaceutical / methods*
Drug Carriers / chemistry*
Drug Compounding / methods*
Microspheres*
Particle Size
Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
Polyvinyl Alcohol / chemistry
Solvents / chemistry

Substances

Drug Carriers
Solvents
Polylactic Acid-Polyglycolic Acid Copolymer
Polyvinyl Alcohol

Grants and funding

The authors are thankful to the Engineering and Physical Sciences Research Council (grant number: EP/N025075/1) for partly funding this work to IDS, VH, and DYSC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.