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


Autoři: R. A. Mensah aff001;  S. B. Kirton aff001;  M. T. Cook aff001;  I. D. Styliari aff001;  V. Hutter aff001;  D. Y. S. Chau aff001
Působiště autorů: Department of Clinical and Pharmaceutical Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, England, United Kingdom aff001;  Department of Biomaterials and Tissue Engineering, Eastman Dental Institute, UCL, London, England, United Kingdom aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222858

Souhrn

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.

Klíčová slova:

Emulsions – Evaporation – Experimental design – Polymers – Scanning electron microscopy – Solvents – Drug delivery – Software design


Zdroje

1. Ferreira J, De Oliviera P and De Silva PM.Controlled drug delivery and ophthalmic applications, Chemical Biochemical Engineering Quartely 2012;26(4):331–343

2. Chau D, Tint N, Collighan R, Griffin M, Dua H, Shakesheff K et al. The visualisation of vitreous using surface modified poly(lactic-co-glycolic acid) microparticles. British Journal of Ophthalmology. 2010;94(5):648–653. doi: 10.1136/bjo.2009.163642 20447968

3. Nihant N, Schugens C, Grandfils C, Jerome R, Teyssie P. Polylactide Microparticles Prepared by Double Emulsion-Evaporation. Journal of Colloid and Interface Science [Internet]. 1995 [cited 14 November 2016];173(1):55–65. https://www.ncbi.nlm.nih.gov/pubmed/7855056

4. Giri T, Choudhary C, Ajazuddin, Alexander A, Badwaik H, Tripathi D. Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery. Saudi Pharmaceutical Journal. 2013;21(2):125–141. doi: 10.1016/j.jsps.2012.05.009 23960828

5. Tamboli V, Mishra GP and Mitra AK. Biodegradable polymers for ocular drug delivery. Advances in Ocular Drug Delivery. 2012;1:65–86

6. Alagusundaram M, Madhu Sudana Chetty C, Umashankari K and Badarinath AV. Microspheres as novel drug delivery system- a review. International Journal of ChemTech Research. 2009;1(3):526–534

7. Patil S, Papadimitrakopoulos F, Burgess D. Dexamethasone-Loaded Poly(Lactic-Co-Glycolic) Acid Microspheres/Poly(Vinyl Alcohol) Hydrogel Composite Coatings for Inflammation Control. Diabetes Technology & Therapeutics. 2004;6(6):887–897.

8. Bourke S, Al-Khalili M, Briggs T, Michniak B, Kohn J, Poole-Warren L. A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications. AAPS PharmSci. 2003;5(4):101–111.

9. Hickey T, Kreutzer D, Burgess D, Moussy F. Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices. Biomaterials. 2002;23(7):1649–1656. doi: 10.1016/s0142-9612(01)00291-5 11922468

10. Chang-Lin J, Attar M, Acheampong A, Robinson M, Whitcup S, Kuppermann B et al. Pharmacokinetics and Pharmacodynamics of a Sustained-Release Dexamethasone Intravitreal Implant. Investigative Opthalmology & Visual Science. 2011;52(1):80.

11. Vikrant K, Gudsoorkar V, Hiremath S, Dolas R and Kashid V. Microspheres—A novel drug delivery system: an overview. International Journal of Pharmaceutical and Chemical Sciences. 2012;1(1):113–128

12. Lai M, Tsiang R. Microencapsulation of acetaminophen into poly(L-lactide) by three different emulsion solvent-evaporation methods. Journal of Microencapsulation. 2005;22(3):261–274. doi: 10.1080/02652040500100261 16019912

13. Khaled K, Sarhan H, Ibrahim M, Ali A, Naguib Y. Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice. AAPS PharmSciTech. 2010;11(2):859–869. doi: 10.1208/s12249-010-9445-5 20490959

14. Prior S, Gamazo C, Irache J, Merkle H, Gander B. Gentamicin encapsulation in PLA/PLGA microspheres in view of treating Brucella infections. International Journal of Pharmaceutics. 2000;196(1):115–125. doi: 10.1016/s0378-5173(99)00448-2 10675713

15. Bodmeier R and McGinity J. The preparation and evaluation of drug-containing poly (DL-lactide) microspheres formed by the solvent evaporation method. Pharmacy Research. 1987;4: 465–71

16. Bible E, Chau D, Alexander M, Price J, Shakesheff K, Modo M. Attachment of stem cells to scaffold particles for intra-cerebral transplantation. Nature Protocols 2009;4:1440–1453 doi: 10.1038/nprot.2009.156 19798079

17. Vysloužil J, Doležel P, Kejdušová M, Mašková E, Mašek J, Lukáč R et al. Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis. Acta Pharmaceutica. 2014;64(4):403–417. doi: 10.2478/acph-2014-0032 25531782

18. Rosca I, Watari F, Uo M. Microparticle formation and its mechanism in single and double emulsion solvent evaporation. Journal of Controlled Release. 2004;99(2):271–280. doi: 10.1016/j.jconrel.2004.07.007 15380636

19. Deshmukh R, Wagh P, Naik J. Solvent evaporation and spray drying technique for micro- and nanospheres/particles preparation: A review. Drying Technology. 2016;34(15):1758–1772.

20. Kemala T, Budianto E, Soegiyono B. Preparation and characterization of microspheres based on blend of poly(lactic acid) and poly(ɛ-caprolactone) with poly(vinyl alcohol) as emulsifier. Arabian Journal of Chemistry. 2012;5(1):103–108.

21. Freitas S, Merkle H, Gander B. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. Journal of Controlled Release. 2005;102(2):313–332. doi: 10.1016/j.jconrel.2004.10.015 15653154

22. Bidone J, Melo A, Bazzo G, Carmignan F, Soldi M, Pires A et al. Preparation and characterization of ibuprofen-loaded microspheres consisting of poly(3-hydroxybutyrate) and methoxy poly (ethylene glycol)-b-poly (D,L-lactide) blends or poly(3-hydroxybutyrate) and gelatin composites for controlled drug release. Materials Science and Engineering: C. 2009;29(2):588–593.

23. Steinberg D, Hunter W. Experimental Design: Review and Comment. Technometrics. 1984;26(2):71.

24. Montgomery D. Experimental Design for Product and Process Design and Development. Journal of the Royal Statistical Society: Series D (The Statistician). 1999;48(2):159–177.

25. Coates N. Determinants of Japan’s Business Success: Some Japanese Executives’ Views. Academy of Management Perspectives. 1988;2(1):69–72.

26. Nair V, Hansen M, Shi J. Statistics in Advanced Manufacturing. Journal of the American Statistical Association. 2000;95(451):1002–1005.

27. Kim K, Kim S, Kim H. Applying the Taguchi method to the optimization for the synthesis of TiO2 nanoparticles by hydrolysis of TEOT in micelles. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2005;254(1–3):99–105.

28. Yang R, Mather R, Fotheringham A. The influence of processing parameters on the structural and mechanical properties of drawn polypropylene fibres: A factorial design approach. Journal of Applied Polymer Science. 2011;124(5):3606–3616.

29. Packianather M, Drake P, Rowlands H. Optimizing the parameters of multilayered feedforward neural networks through Taguchi design of experiments. Quality and Reliability Engineering International. 2000;16(6):461–473.

30. Huang M, Hung Y, Yang Z. Validation of a method using Taguchi, response surface, neural network, and genetic algorithm. Measurement. 2016; 94:284–294.

31. Bement T, Ross P. Taguchi Techniques for Quality Engineering. Technometrics. 1989;31(2):254.

32. Riahi S, Nazari A, Zaarei D, Khalaj G, Bohlooli H, Kaykha M. Compressive strength of ash-based geopolymers at early ages designed by Taguchi method. Materials & Design. 2012; 37:443–449.

33. Krishnamoorthy K, Mahalingam M. Fabrication and optimization of camptothecin loaded Eudragit S 100 nanoparticles by Taguchi L4 orthogonal array design. International Journal of Pharmaceutical Investigation. 2015;5(3):147. 26258056

34. Torkaman R, Soltanieh M, Kazemian H. Optimization of Parameters for Synthesis of MFI Nanoparticles by Taguchi Robust Design. Chemical Engineering & Technology. 2010;33(6):902–910.

35. Vysloužil J, Doležel P, Kejdušová M, Mašková E, Mašek J, Lukáč R et al. Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis. Acta Pharmaceutica. 2014;64(4):403–417. doi: 10.2478/acph-2014-0032 25531782

36. Sharma N, Madan P and Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian Journal of Pharmaceutical Sciences. 2016;11(3):404–416

37. Determan A, Trewyn B, Lin V, Nilsen-Hamilton M, Narasimhan B. Encapsulation, stabilization, and release of BSA-FITC from polyanhydride microspheres. Journal of Controlled Release. 2004;100(1):97–109. doi: 10.1016/j.jconrel.2004.08.006 15491814

38. Pang J, Ansari M, Zaroog O, Ali M, Sapuan S. Taguchi design optimization of machining parameters on the CNC end milling process of halloysite nanotube with aluminium reinforced epoxy matrix (HNT/Al/Ep) hybrid composite. HBRC Journal. 2014;10(2):138–144.

39. Zahn D. An Empirical Study of the Half-Normal Plot. Technometrics. 1975;17(2):201.

40. Tan C, Anarjan N, Malmiri H, Nehdi I, Sbihi H, Al-Resayes S. Effects of homogenization process parameters on physicochemical properties of astaxanthin nanodispersions prepared using a solvent-diffusion technique. International Journal of Nanomedicine. 2015;:1109.

41. Jafari S, Assadpoor E, He Y, Bhandari B. Re-coalescence of emulsion droplets during high-energy emulsification. Food Hydrocolloids. 2008;22(7):1191–1202.

42. Zweers M, Grijpma D, Engbers G, Feijen J. The preparation of monodisperse biodegradable polyester nanoparticles with a controlled size. Journal of Biomedical Materials Research. 2003;66B(2):559–566.

43. Wagh V, Apar D. Cyclosporine A Loaded PLGA Nanoparticles for Dry Eye Disease:In VitroCharacterization Studies. Journal of Nanotechnology. 2014;2014:1–10.

44. Hoffart V, Ubrich N, Simonin C, Babak V, Vigneron C, Hoffman M et al. Low Molecular Weight Heparin-Loaded Polymeric Nanoparticles: Formulation, Characterization, and Release Characteristics. Drug Development and Industrial Pharmacy. 2002;28(9):1091–1099. doi: 10.1081/DDC-120014576 12455468

45. Quintanar-Guerrero D, Fessi H, Allémann E, Doelker E. Influence of stabilizing agents and preparative variables on the formation of poly(d,l-lactic acid) nanoparticles by an emulsification-diffusion technique. International Journal of Pharmaceutics. 1996;143(2):133–141.

46. Mondal N, Samanta A, Pal T, Ghosal S. Effect of Different Formulation Variables on Some Particle Characteristics of Poly (DL-lactide-co-glycolide) Nanoparticles. Yakugaku Zasshi. 2008;128(4):595–601. doi: 10.1248/yakushi.128.595 18379176

47. Valizadeh H, Jelvehgari M, Nokhodchi A, Rezapour M. Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method. Indian Journal of Pharmaceutical Sciences. 2010;72(1):72. 20582193

48. Caetano L, Almeida A, Gonçalves L. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation. Marine Drugs. 2016;14(5):90.

49. Rodriguez L, Avalos A, Chiaia N, Nadarajah A. Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique. AAPS PharmSciTech. 2016;18(4):1084–1094. doi: 10.1208/s12249-016-0677-x 27995463

50. Panyam J, Dali M, Sahoo S, Ma W, Chakravarthi S, Amidon G et al. Polymer degradation and in vitro release of a model protein from poly(d,l-lactide-co-glycolide) nano- and microparticles. Journal of Controlled Release. 2003;92(1–2):173–187. doi: 10.1016/s0168-3659(03)00328-6 14499195


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden