AAPS PharmSciTech

, 20:14 | Cite as

Use of Risk Assessment and Plackett–Burman Design for Developing Resveratrol Spray-Dried Emulsions: a Quality-by-Design Approach

  • Pontip Benjasirimongkol
  • Suchada Piriyaprasarth
  • Kunikazu Moribe
  • Pornsak SriamornsakEmail author
Research Article


In this study, the resveratrol spray-dried emulsions were developed using a quality-by-design approach. Further, the product and process factors that affected the quality of the spray-dried emulsions were analyzed and illustrated using an Ishikawa diagram. The product and process risks were prioritized using a risk-ranking system. The low methoxyl pectin (LMP) amount, caprylic/capric glyceride (CCG) amount, homogenization time, homogenization speed, inlet temperature, pump speed, drying airspeed, and de-blocking speed were observed to be the eight highest risk factors. Further, the criticality of these eight factors on the responses was determined using the Plackett–Burman design. Increasing the LMP amount increased the particle size, whereas increasing the CCG amount enhanced the drug-loading capacity and drug dissolution at 5-min intervals (Q5) and decreased the moisture content. Q5 was positively affected by the homogenization speed and pump speed; however, it was negatively affected by the LMP amount. The spraying efficiency was affected by the pump speed and the LMP amount. Further, the risk level of the homogenization time, inlet temperature, drying airspeed, and de-blocking speed were reduced. However, the LMP amount, CCG amount, homogenization speed, and pump speed were observed to remain at high risk and require further investigation. The risk assessment and Plackett–Burman design mitigated the risks and identified the critical factors that affected the quality of the resveratrol spray-dried emulsions and the spray-drying process.


quality-by-design risk assessment Plackett–Burman design resveratrol spray-dried emulsion 



The authors would like to thank the Faculty of Pharmacy, Silpakorn University, Thailand for providing partial financial support.

Compliance with Ethical Standards

Conflict of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material

12249_2018_1220_MOESM1_ESM.pdf (72 kb)
Fig. S1 (PDF 72 kb)


  1. 1.
    Novelle MG, Wahl D, Diéguez C, Bernier M, de Cabo R. Resveratrol supplementation: where are we now and where should we go? Ageing Res Rev. 2015;21:1–15.CrossRefGoogle Scholar
  2. 2.
    Robinson K, Mock C, Liang D. Pre-formulation studies of resveratrol. Drug Dev Ind Pharm. 2015;41:1464–9.CrossRefGoogle Scholar
  3. 3.
    Wan Z-L, Wang J-M, Wang L-Y, Yang X-Q, Yuan Y. Enhanced physical and oxidative stabilities of soy protein-based emulsions by incorporation of a water-soluble stevioside–resveratrol complex. J Agric Food Chem. 2013;61:4433–40.CrossRefGoogle Scholar
  4. 4.
    Allan KE, Lenehan CE, Ellis AV. UV light stability of α-cyclodextrin/resveratrol host–guest complexes and isomer stability at varying pH. Aust J Chem. 2009;62:921–6.CrossRefGoogle Scholar
  5. 5.
    Davidov-Pardo G, McClements DJ. Resveratrol encapsulation: designing delivery systems to overcome solubility, stability and bioavailability issues. Trends Food Sci Technol. 2014;38:88–103.CrossRefGoogle Scholar
  6. 6.
    McClements DJ, Li Y. Structured emulsion-based delivery systems: controlling the digestion and release of lipophilic food components. Adv Colloid Interf Sci. 2010;159:213–28.CrossRefGoogle Scholar
  7. 7.
    Norton JE, Gonzalez Espinosa Y, Watson RL, Spyropoulos F, Norton IT. Functional food microstructures for macronutrient release and delivery. Food Funct:Royal Soc Chem. 2015;6:663–78.CrossRefGoogle Scholar
  8. 8.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Pharmaceutical Development: Q8(R2). 2009. Accessed 15 Nov 2016.
  9. 9.
    Piriyaprasarth S, Sriamornsak P. Effect of source variation on drug release from HPMC tablets: linear regression modeling for prediction of drug release. Int J Pharm. 2011;411:36–42.CrossRefGoogle Scholar
  10. 10.
    Van Buskirk GA, Asotra S, Balducci C, Basu P, DiDonato G, Dorantes A, et al. Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm. AAPS PharmSciTech. 2014;15:665–93.CrossRefGoogle Scholar
  11. 11.
    Weissman SA, Anderson NG. Design of experiments (DoE) and process optimization. A review of recent publications. Org Process Res Dev. 2015;19:1605–33.CrossRefGoogle Scholar
  12. 12.
    Plackett RL, Burman JP. The design of optimum multifactorial experiments. Biometrika. 1946;33:305–25.CrossRefGoogle Scholar
  13. 13.
    Deshmukh RK, Naik JB. Optimization of spray-dried diclofenac sodium-loaded microspheres by screening design. Dry Technol. 2016;34:1593–603.CrossRefGoogle Scholar
  14. 14.
    Verma U, Naik JB, Patil JS, Yadava SK. Screening of process variables to enhance the solubility of famotidine with 2-hydroxypropyl-β-cyclodextrin & PVP K-30 by using Plackett–Burman design approach. Mater Sci Eng C. 2017;77:282–92.CrossRefGoogle Scholar
  15. 15.
    Aven T. Improving risk characterisations in practical situations by highlighting knowledge aspects, with applications to risk matrices. Reliab Eng Syst Saf. 2017;167:42–8.CrossRefGoogle Scholar
  16. 16.
    Anderson M, Whitcomb PJ. DOE simplified: practical tools for effective experimentation. 2nd ed. New York: Productivity Press; 2007.Google Scholar
  17. 17.
    Cal K, Sollohub K. Spray drying technique. I: hardware and process parameters. J Pharm Sci. 2010;99:575–86.CrossRefGoogle Scholar
  18. 18.
    Sollohub K, Cal K. Spray drying technique: II. Current applications in pharmaceutical technology. J Pharm Sci. 2010;99:587–97.CrossRefGoogle Scholar
  19. 19.
    Castel V, Rubiolo AC, Carrara CR. Brea gum as wall material in the microencapsulation of corn oil by spray drying: effect of inulin addition. Food Res Int. 2018;103:76–83.CrossRefGoogle Scholar
  20. 20.
    Carmona PAO, Garcia LC, Ribeiro JA de A, Valadares LF, Marçal A de F, de França LF, et al. Effect of solids content and spray-drying operating conditions on the carotenoids microencapsulation from pressed palm fiber oil extracted with supercritical CO2. Food Bioprocess Technol. 2018;11:1703–8.CrossRefGoogle Scholar
  21. 21.
    Gu B, Linehan B, Tseng Y-C. Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions. Int J Pharm. 2015;491:208–17.CrossRefGoogle Scholar
  22. 22.
    Jafari SM, Assadpoor E, Bhandari B, He Y. Nano-particle encapsulation of fish oil by spray drying. Food Res Int. 2008;41:172–83.CrossRefGoogle Scholar
  23. 23.
    Tonon RV, Brabet C, Hubinger MD. Influence of process conditions on the physicochemical properties of açai (Euterpe oleraceae Mart.) powder produced by spray drying. J Food Eng. 2008;88:411–8.CrossRefGoogle Scholar
  24. 24.
    Masters K. Spray drying handbook. 5th ed. Essex: Longman Scientific & Technical; 1991.Google Scholar
  25. 25.
    Carneiro HCF, Tonon RV, Grosso CRF, Hubinger MD. Encapsulation efficiency and oxidative stability of flaxseed oil microencapsulated by spray drying using different combinations of wall materials. J Food Eng. 2013;115:443–51.CrossRefGoogle Scholar
  26. 26.
    Tonon RV, Grosso CRF, Hubinger MD. Influence of emulsion composition and inlet air temperature on the microencapsulation of flaxseed oil by spray drying. Food Res Int. 2011;44:282–9.CrossRefGoogle Scholar
  27. 27.
    de Barros Fernandes RV, Marques GR, Borges SV, Botrel DA. Effect of solids content and oil load on the microencapsulation process of rosemary essential oil. Ind Crop Prod. 2014;58:173–81.CrossRefGoogle Scholar
  28. 28.
    Kavousi HR, Fathi M, Goli SAH. Stability enhancement of fish oil by its encapsulation using a novel hydrogel of cress seed mucilage/chitosan. Int J Food Prop. 2017;20:1890–900.Google Scholar
  29. 29.
    Frascareli EC, Silva VM, Tonon RV, Hubinger MD. Effect of process conditions on the microencapsulation of coffee oil by spray drying. Food Bioprod Process. 2012;90:413–24.CrossRefGoogle Scholar
  30. 30.
    Botrel DA, Borges SV, Fernandes RVDB, Do Carmo EL. Optimization of fish oil spray drying using a protein:inulin system. Dry Technol. 2014;32:279–90.CrossRefGoogle Scholar
  31. 31.
    Montgomery DC. Design and Analysis of experiments. 8th ed. New York: John Wiley & Sons; 2012.Google Scholar
  32. 32.
    Baek I, Kim J-S, Ha E-S, Choo G-H, Cho W, Hwang S-J, et al. Oral absorption of a valsartan-loaded spray-dried emulsion based on hydroxypropylmethyl cellulose. Int J Biol Macromol. 2014;69:222–8.CrossRefGoogle Scholar
  33. 33.
    Burapapadh K, Takeuchi H, Sriamornsak P. Novel pectin-based nanoparticles prepared from nanoemulsion templates for improving in vitro dissolution and in vivo absorption of poorly water-soluble drug. Eur J Pharm Biopharm. 2012;82:250–61.CrossRefGoogle Scholar
  34. 34.
    Rao MRP, Aghav SS. Spray-dried redispersible emulsion to improve oral bioavailability of itraconazole. J Surfactant Deterg. 2014;17:807–17.CrossRefGoogle Scholar
  35. 35.
    Bilancetti L, Poncelet D, Loisel C, Mazzitelli S, Claudio N. A statistical approach to optimize the spray drying of starch particles: application to dry powder coating. AAPS PharmSciTech. 2010;11:1257–67.CrossRefGoogle Scholar
  36. 36.
    Chegini GR, Ghobadian B. Effect of spray-drying conditions on physical properties of orange juice powder. Dry Technol. 2005;23:657–68.CrossRefGoogle Scholar
  37. 37.
    Sosnik A, Seremeta KP. Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers. Adv Colloid Interf Sci. 2015;223:40–54.CrossRefGoogle Scholar
  38. 38.
    Pallagi E, Karimi K, Ambrus R, Szabó-Révész P, Csóka I. New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach. Int J Pharm. 2016;511:151–60.CrossRefGoogle Scholar
  39. 39.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Quality Risk Management: Q9. 2005. Accessed 1 Dec 2016.

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Pontip Benjasirimongkol
    • 1
    • 2
    • 3
  • Suchada Piriyaprasarth
    • 1
    • 2
  • Kunikazu Moribe
    • 3
  • Pornsak Sriamornsak
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacySilpakorn UniversityNakhon PathomThailand
  2. 2.Pharmaceutical Biopolymer Group (PBiG), Faculty of PharmacySilpakorn UniversityNakhon PathomThailand
  3. 3.Graduate School of Pharmaceutical SciencesChiba UniversityChibaJapan
  4. 4.Academy of ScienceRoyal Society of ThailandBangkokThailand

Personalised recommendations