PLA/PLGA nanoparticles prepared by nano spray drying

  • Cordin ArpagausEmail author



Spray drying is a relatively simple, fast, reproducible and scalable drying technology that is suitable for drying heat-sensitive biopharmaceutical compounds. In view of the rapid progress of nanoencapsulation technologies in the pharmaceutical sector, nano spray drying is used in research to improve the powder formulation and release of active ingredients. The Nano Spray Dryer B-90 of the Swiss company Büchi Labortechnik AG extends the size of the powder particles produced into the nanometer scale with narrow size distributions and high encapsulation efficiency.

Area covered

This study explains the special nano spray drying technology and discusses the influence of the respective process parameters on the powder properties. Applications of nano spray drying for the formulation and encapsulation of active ingredients in PLA/PLGA biopolymers are investigated and discussed. Optimized process parameters for the application of nano spray drying of similar substances are presented.

Expert opinion

The analyzed studies show the possibility of producing PLGA particles from approx. 2 μm to below 200 nm by nano spray drying, as well as the encapsulation of various active ingredients in spherical particles and nano-in-nanoparticle composite structures made of PLGA polymers for controlled drug delivery systems. The researched applications are primarily in the therapeutic field, such as the treatment of inhalation diseases, inflammations, cancer, immune diseases, genetic disorders, the regulation of vasodilatation or the surface coating of medical implants with biocompatible PLGA nanoparticles.


Nano spray drying Nanoparticles Encapsulation Drug delivery PLA PLGA 


Compliance with ethical standards

Conflict of the interest

Cordin Arpagaus declares that he has no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. Abdel-Mageed HM, Fouad SA, Teaima MH, Abdel-Aty AM, Fahmy AS, Shaker DS, Mohamed SA (2019) Optimization of nano spray drying parameters for production of α-amylase nanopowder for biotheraputic applications using factorial design. Dry Technol. Google Scholar
  2. Amsalem O, Nassar T, Benhamron S, Lazarovici P, Benita S, Yavin E (2017) Solid nano-in-nanoparticles for potential delivery of siRNA. J Control Release 257:144–155CrossRefGoogle Scholar
  3. Anzar N, Mirza MA, Anwer K, Khuroo T, Alshetaili AS, Alshahrani SM, Meena J, Hasan N, Talegaonkar S, Panda AK, Iqbal Z (2018) Preparation, evaluation and pharmacokinetic studies of spray dried PLGA polymeric submicron particles of simvastatin for the effective treatment of breast cancer. J Mol Liq 249:609–616CrossRefGoogle Scholar
  4. Arpagaus C (2009) Food technology at the nano scale: advances in spray drying. Food Eng. Ingredients 34:26–27Google Scholar
  5. Arpagaus C (2011) Nano spray dryer B-90: literature review and applications, best@buchi Information Bulletin, Number 63/2011Google Scholar
  6. Arpagaus C (2012) A novel laboratory-scale spray dryer to produce nanoparticles. Dry Technol 30:1113–1121CrossRefGoogle Scholar
  7. Arpagaus C (2018a) Pharmaceutical particle engineering via nano spray drying—process parameters and application examples on the laboratory-scale. Int J Med Nano Res. Google Scholar
  8. Arpagaus C (2018b) Nano spray drying of pharmaceuticals. In: IDS 2018—21st international drying symposium, Valencia, Spain, 11–14 Sept 2018. pp 1–8Google Scholar
  9. Arpagaus C (2018c) A short review on nano spray drying of pharmaceuticals. Nanomed Nanosci Res 546:1–5Google Scholar
  10. Arpagaus C (2018d) Nano spray drying of pharmaceuticals. Am J Nanotechnol Nanomed 1:64–68Google Scholar
  11. Arpagaus C Schafroth N (2007) Spray dried biodegradable polymers as target material for controlled drug delivery, best@buchi Information Bulletin, Number 46/2007Google Scholar
  12. Arpagaus C, Meuri M (2010) Laboratory scale spray drying of inhalable particles: a review. Respir Drug Deliv 2:469–476Google Scholar
  13. Arpagaus C, Schafroth N (2008) Spray drying of biodegradable polymers in laboratory scale. In: XVIth international conference on bioencapsulation, Dublin, Ireland, 4–6 Sept 2008. pp 1–4Google Scholar
  14. Arpagaus C, Schafroth N (2011) Spray dried biodegradable polymers for controlled drug delivery systems. Eur Ind Pharm 11:10–13Google Scholar
  15. Arpagaus C, Friess W, Schmid K (2009) Nano spray drying in laboratory scale. GIT Lab J 11–12:30–31Google Scholar
  16. Arpagaus C, Schafroth N, Meuri M (2010a) Laboratory scale spray drying of inhalable drugs: a review, best@buchi Information Bulletin, Number 59/2010Google Scholar
  17. Arpagaus C, Schafroth N, Meuri M (2010b) Laboratory scale spray drying of lactose: a review, best@buchi Information Bulletin, Number 57/2010Google Scholar
  18. Arpagaus C, Rütti D, Meuri M (2013) Chapter 18: enhanced solubility of poorly soluble drugs via spray drying. In: Douroumis D, Fahr A (eds) Drug delivery strategies for poorly water-soluble drugs. Wiley, New York, pp 551–585CrossRefGoogle Scholar
  19. Arpagaus C, John P, Collenberg A, Rütti D (2017) Chapter 10: Nanocapsules formation by nano spray drying. In: Jafari SM (ed) Nanoencapsulation technologies for the food and nutraceutical industries. Elsevier Inc., Amsterdam, pp 346–401CrossRefGoogle Scholar
  20. Arpagaus C, Collenberg A, Rütti D, Assadpour E, Jafari SM (2018) Nano spray drying for encapsulation of pharmaceuticals. Int J Pharm 546:194–214CrossRefGoogle Scholar
  21. Assadpour E, Jafari SM (2019) Advances in spray-drying encapsulation of food bioactive ingredients: from microcapsules to nanocapsules. Annu Rev Food Sci Technol 10:8–29CrossRefGoogle Scholar
  22. Baghdan E, Pinnapireddy SR, Vögeling H, Schäfer J, Eckert AW, Bakowsky U (2018) Nano spray drying: a novel technique to prepare well-defined surface coatings for medical implants. J Drug Deliv Sci Technol 48:145–151CrossRefGoogle Scholar
  23. Baras B, Benoit M-A, Gillard J (2000) Parameters influencing the antigen release from spray-dried poly(dl-lactide) microparticles. Int J Pharm 200:133–145CrossRefGoogle Scholar
  24. Beck-Broichsitter M, Schweiger C, Schmehl T, Gessler T, Seeger W, Kissel T (2012) Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. J Control Release 158:329–335CrossRefGoogle Scholar
  25. Beck-Broichsitter M, Paulus IE, Greiner A, Kissel T (2015a) Modified vibrating-mesh nozzles for advanced spray-drying applications. Eur J Pharm Biopharm 92:96–101CrossRefGoogle Scholar
  26. Beck-Broichsitter M, Strehlow B, Kissel T (2015b) Direct fractionation of spray-dried polymeric microparticles by inertial impaction. Powder Technol 286:311–317CrossRefGoogle Scholar
  27. Bege N, Renette T, Endres T, Beck-Broichsitter M, Hänggi D, Kissel T (2013) In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm. Eur J Pharm Biopharm 84:99–105CrossRefGoogle Scholar
  28. Benita S, Amsalem O, Nassar T (2016) Nano delivery systems for SiRNA, US Patent 9421173 B2Google Scholar
  29. Blanco MD, Sastre RL, Teijón C, Olmo R, Teijón JM (2005) 5-Fluorouracil-loaded microspheres prepared by spray-drying poly(d, l-lactide) and poly(lactide-co-glycolide) polymers: characterization and drug release. J Microencapsul 22:671–682CrossRefGoogle Scholar
  30. Bodmeier R, Chen H (1988) Preparation of biodegradable poly(±)lactide microparticles using a spray-drying technique. J Pharm, Pharmacol, p 40Google Scholar
  31. Büchi Labortechnik AG (2009) Nano spray dryer B-90 application note: PLA (Polylactic acid) R 202 HGoogle Scholar
  32. Büchi Labortechnik AG (2010) Nano spray dryer B-90 Brochure, Flawil, Switzerland,. 11592236 en 1012.
  33. Büchi Labortechnik AG (2011) Application Note 002/2011 (Version A): Spray drying of polylactic acid (PLA) with the Nano Spray Dryer B-90Google Scholar
  34. Büchi Labortechnik AG (2017) PLGA sub-micron particles by Nano Spray Drying, Application Note No.273/2017Google Scholar
  35. Bürki K, Jeon I, Arpagaus C, Betz G (2011) New insights into respirable protein powder preparation using a nano spray dryer. Int J Pharm 408:248–256CrossRefGoogle Scholar
  36. Conte U, Conti B, Giunchedi P, Maggi L (1994) Spray dried polylactide microsphere preparation: influence of the technological parameters. Drug Dev Ind Pharm 20:235–258CrossRefGoogle Scholar
  37. Dahili LA, Feczkó T (2015) Cross-linking of horseradish peroxidase enzyme to fine particles generated by nano spray dryer B-90. Period. Polytech. Chem. Eng. 59:209–214CrossRefGoogle Scholar
  38. Dahili LA, Nagy E, Feczko T (2017) 2,4-Dichlorophenol enzymatic removal and its kinetic study using horseradish peroxidase crosslinked to nano spray-dried poly(lactic-co-glycolic acid) fine particles. J Microbiol Biotechnol 27:768–774CrossRefGoogle Scholar
  39. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–522CrossRefGoogle Scholar
  40. Draheim C, de Crécy F, Hansen S, Collnot E-M, Lehr C-M (2015) a design of experiment study of nanoprecipitation and nano spray drying as processes to prepare PLGA nano- and microparticles with defined sizes and size distributions. Pharm Res 32:2609–2624Google Scholar
  41. EVONIK (2011) RESOMER® Product rangeGoogle Scholar
  42. Feng S-S, Mu L, Win K, Huang G (2004) Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. Curr Med Chem 11:413–424CrossRefGoogle Scholar
  43. Feng AL, Boraey MA, Gwin MA, Finlay PR, Kuehl PJ, Vehring R (2011) Mechanistic models facilitate efficient development of leucine containing microparticles for pulmonary drug delivery. Int J Pharm 409:156–163CrossRefGoogle Scholar
  44. Fu YJ, Mi FL, Wong TB, Shyu SS (2001) Characteristic and controlled release of anticancer drug loaded poly (d, l-lactide) microparticles prepared by spray drying technique. J Microencapsul 18:733–747CrossRefGoogle Scholar
  45. Garlotta D (2001) A literature review of poly(lactic acid). J Polym Environ 9:63–84CrossRefGoogle Scholar
  46. Heng D, Lee SH, Ng WK, Tan RBH (2011) The nano spray dryer B-90. Expert Opin Drug Deliv 8:965–972CrossRefGoogle Scholar
  47. Johansen P, Merkle HP, Gander B (2000) Technological considerations related to the up-scaling of protein microencapsulation by spray-drying. Eur J Pharm Biopharm 50:413–417CrossRefGoogle Scholar
  48. Kaialy W, Al Shafiee M (2016) Recent advances in the engineering of nanosized active pharmaceutical ingredients: promises and challenges. Adv Coll Interface Sci 228:71–91CrossRefGoogle Scholar
  49. Kulkarni RK, Pani KC, Neuman C, Leonard F (1966) Polylactic acid for surgical implants. JAMA Surg 93:839–843Google Scholar
  50. Lee SH, Heng D, Ng WK, Chan H-K, Tan RBH (2011) Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy. Int J Pharm 403:192–200CrossRefGoogle Scholar
  51. Li X, Anton N, Arpagaus C, Belleteix F, Vandamme TF (2010) Nanoparticles by spray drying using innovative new technology: the Büchi Nano Spray Dryer B-90. J Control Release 147:304–310CrossRefGoogle Scholar
  52. Masters K (1991) Spray drying handbook, 5th edn. Longman Scientific & Technical, HarlowGoogle Scholar
  53. O’Hara P, Hickey AJ (2000) Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: manufacture and characterization. Pharm Res 17:955–961CrossRefGoogle Scholar
  54. Pamujula S, Graves RA, Freeman T, Srinivasan V, Bostanian LA, Kishore V, Mandal TK (2004) Oral delivery of spray dried PLGA/amifostine nanoparticles. J Pharm Pharmacol 56:1119–1125CrossRefGoogle Scholar
  55. Panda A, Meena J, Katara R, Majumdar DK (2016) Formulation and characterization of clozapine and risperidone co-entrapped spray-dried PLGA nanoparticles. Pharm Dev Technol 21:43–53CrossRefGoogle Scholar
  56. Pavanetto F, Genta I, Giunchedi P, Conti B (1993) Evaluation of spray drying as a method for polylactide and polylactide-co-glycolide microsphere preparation. J Microencapsul 10:487–497CrossRefGoogle Scholar
  57. Rivera PA, Martinez-Oharriz MC, Rubio M, Irache JM, Espuelas S (2004) Fluconazole encapsulation in PLGA microspheres by spray-drying. J Microencapsul 21:203–211CrossRefGoogle Scholar
  58. Schafroth N (2010) Nano-encapsulation of different actives in biodegradable polymers with Nano Spray Dryer B-90, Application Sheet No. 20100201, Büchi Labortechnik AGGoogle Scholar
  59. Schafroth N, Arpagaus C, Jadhav UY, Makne S, Douroumis D (2012) Nano and microparticle engineering of water insoluble drugs using a novel spray-drying process. Coll Surf B Biointerfaces 90:8–15CrossRefGoogle Scholar
  60. Schmid K (2011) Spray drying of protein precipitates and Evaluation of the Nano Spray Dryer B-90. PhD Thesis, Ludwig-Maximilians-University, MunichGoogle Scholar
  61. Schmid K, Arpagaus C, Friess W (2009) Evaluation of a vibrating mesh spray dryer for preparation of submicron particles. Respir Drug Deliv 30:323–326Google Scholar
  62. Schmid K, Arpagaus C, Friess W (2011) Evaluation of the nano spray dryer B-90 for pharmaceutical applications. Pharm Dev Technol 16:287–294CrossRefGoogle Scholar
  63. Schöttle IA (2006) Sprühgetrocknete Polylaktid, Poly(laktid-co-glykolid) Mikropartikel zur Steuerung der Freisetzung aus pulmonalen Arzneiformen, Dissertation. Johannes Gutenberg-Universität MainzGoogle Scholar
  64. Schoubben A, Blasi P, Marenzoni ML, Barberini L, Giovagnoli S, Cirotto C, Ricci M (2013) Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization. Eur J Pharm Biopharm 83:388–395CrossRefGoogle Scholar
  65. Sharma S, Parmar A, Kori S, Sandhir R (2016) PLGA-based nanoparticles: a new paradigm in biomedical applications. TrAC Trends Anal Chem 80:30–40CrossRefGoogle Scholar
  66. Torge A, Grützmacher P, Mücklich F, Schneider M (2017) The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles. Eur J Pharm Sci 104:171–179CrossRefGoogle Scholar
  67. Wagenaar BW, Müller BW (1994) Piroxicam release from spray-dried biodegradable microspheres. Biomaterials 15:49–54CrossRefGoogle Scholar
  68. Wan F, Yang M (2016) Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying. Int J Pharm 498:82–95CrossRefGoogle Scholar
  69. Wang FJ, Wang CH (2002) Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres. J Microencapsul 19:495–510CrossRefGoogle Scholar
  70. Wong TW (2015) Nanospray drying technology: existing limitations and future challenges. Recent Pat Drug Deliv Formul 9:185–186CrossRefGoogle Scholar
  71. Wong TW, John P (2015) Advances in spray drying technology for nanoparticle formation. In: Aliofkhazraei M (ed) Handbook of nanoparticles. Springer International Publishing, New York, pp 1–16Google Scholar
  72. Youan BBC (2004) Microencapsulation of superoxide dismutase into biodegradable microparticles by spray-drying. Drug Deliv J Deliv Target Ther Agents 11:209–214Google Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  1. 1.NTB University of Applied Sciences of Technology BuchsInstitute for Energy SystemsBuchsSwitzerland

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