Skip to main content

Advertisement

SpringerLink
Log in

Formulation of Resveratrol-Loaded Polycaprolactone Inhalable Microspheres Using Tween 80 as an Emulsifier: Factorial Design and Optimization

  • Research Article
  • Inhaled Drug Delivery of Biologics for Therapeutic and Vaccination
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Resveratrol (RSV) is a bioactive phytoconstituent that has potential applications in respiratory diseases. However, poor oral bioavailability is the major hurdle to its clinical use. In the present work, resveratrol-loaded polycaprolactone (PCL) inhalable microspheres (MSs) were formulated to improve their therapeutic potential. The inhalable microspheres were formulated using the emulsion-solvent evaporation method. In this research, inhalable resveratrol microspheres were prepared using Tween 80 in place of polyvinyl alcohol which formed insoluble lumps. A 32 factorial design was applied taking polymer (PCL) and emulsifier (Tween 80) as independent variables and drug loading (DL) and encapsulation efficiency (EE) as dependent variables. The DL and EE of the optimized formulation were found to be 30.6% and 63.84% respectively. The in vitro aerosolization study performed using the Anderson cascade impactor showed that the fine particle fraction (FPF) of optimized resveratrol polycaprolactone microspheres (RSV-PCL-MSs) blended with lactose, and RSV-PCL-MSs were significantly higher than those of the pure drugs. The MMADT (theoretical mass median aerodynamic diameter) of optimized RSV-PCL-MSs was found to be 3.25 ± 1.15. The particle size of microspheres was within the inhalable range, i.e., between 1 and 5 µm. The morphological analysis showed spherical-shaped particles with smooth surfaces. The in vitro release study showed sustained drug release from the microspheres for up to 12 h. The study concluded that resveratrol-loaded inhalable microspheres may be an efficient delivery system to treat COPD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Data Availability

All data generated in this research work is given in the manuscript.

References

  1. Mathioudakis AG, Vanfleteren LEGW, Lahousse L. Current developments and future directions in COPD. Eur Respir Rev. 2020;29:1–12. https://doi.org/10.1183/16000617.0289-2020.

    Article  Google Scholar 

  2. Murgia N, Gambelunghe A. Occupational COPD—the most under-recognized occupational lung disease? Respirology. 2022;27(6):399–410.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Scaramuzzo G, Ottaviani I, Volta CA, Spadaro S. Mechanical ventilation and COPD: from pathophysiology to ventilatory management. Minerva Med. 2022;113(3):460–70.

    Article  PubMed  Google Scholar 

  4. Lai HC, Lin TL, Chen TW, Kuo YL, Chang CJ, Wu TR, et al. Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide. Gut. 2022;71(2):309–21.

    Article  CAS  PubMed  Google Scholar 

  5. Uwagboe I, Adcock IM, Lo Bello F, Caramori G, Mumby S. New drugs under development for COPD. Minerva Med. 2022;113(3):471–96.

    Article  PubMed  Google Scholar 

  6. Mayuri A, Shilpa S. In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting. Drug Dev Ind Pharm. 2017;43(10):1686–93. https://doi.org/10.1080/03639045.2017.1338721.

    Article  CAS  Google Scholar 

  7. Su M, Zhao W, Xu S. Resveratrol in treating diabetes and its cardiovascular complications : a review of its mechanisms of action. Antioxidants. 2022;11:1085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen M, He C, Zhu K, Chen Z, Meng Z, Jiang X, et al. Resveratrol ameliorates polycystic ovary syndrome via transzonal projections within oocyte-granulosa cell communication. Theranostics. 2022;12(2):782–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Li J, Zeng X, Yang F, Wang L, Luo X, Liu R, et al. Resveratrol : potential application in sepsis. Front. Pharmacol. 2022;13(2):821358. https://doi.org/10.3389/fphar.2022.821358

  10. Li T, Tan Y, Ouyang S, He J, Liu L. Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis. Gene. 2022;808:145968. https://doi.org/10.1016/j.gene.2021.145968.

    Article  CAS  PubMed  Google Scholar 

  11. Galiniak S, Aebisher D, Bartusik-aebisher D. Health benefits of resveratrol administration. Acta Biochim Pol. 2019;66(1):13–21. https://doi.org/10.18388/abp.2018_2749

  12. Hecker A, Luze H, Schellnegger M, Hofmann E. The impact of resveratrol on skin wound healing, scarring, and aging. Int wound J. 2022;19:9–28.

    Article  PubMed  Google Scholar 

  13. Beijers RJHCG, Gosker HR, Schols AMWJ. Resveratrol for patients with chronic obstructive pulmonary disease: hype or hope? Curr Opin Clin Nutr Metab Care. 2018;21(2):138–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Leis K, Gałązka P, Kazik J, Jamrożek T, Bereźnicka W, Czajkowski R. Resveratrol in the treatment of asthma based on an animal model. Adv Dermatology Allergol. 2022;3:433–8.

    Article  Google Scholar 

  15. Joshi PA, Bothiraja C, Pawar AP. Fabrication and application of dimyristoyl phosphatidylcholine biomaterial-based nanocochleates dry powder inhaler for controlled release resveratrol delivery. 2021;47(7):1–12.

  16. Zhang LX, Li CX, Kakar MU, Khan MS, Wu PF, Amir RM, et al. Resveratrol (RV): a pharmacological review and call for further research. Biomed Pharmacother. 2021;143(October):112164. https://doi.org/10.1016/j.biopha.2021.112164.

    Article  CAS  PubMed  Google Scholar 

  17. Baloira A, Abad A, Fuster A. Lung deposition and inspiratory flow rate in patients with chronic obstructive pulmonary disease using different inhalation devices: a systematic literature review and expert opinion (Int J Chron Obstruct Pulmon Dis., (2021) 16, (1021–1033), https://doi.org/10.2147/COPD. Int J Chron Obs Pulmon Dis. 2021;16:2243.

  18. Shetty N, Cipolla D, Park H, Zhou QT. Physical stability of dry powder inhaler formulations. Expert Opin Drug Deliv. 2020;17(1):77–96.

    Article  CAS  PubMed  Google Scholar 

  19. Nainwal N, Sharma Y, Jakhmola V. Dry powder inhalers of antitubercular drugs. Tuberculosis. 2022;135(06): 102228.

    Article  CAS  PubMed  Google Scholar 

  20. Lavorini F, Chudek J, Gálffy G, Pallarés-Sanmartin A, Pelkonen AS, Rytilä P, et al. Switching to the dry-powder inhaler Easyhaler®: a narrative review of the evidence. Pulm Ther. 2021;7(2):409–27.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cheng SN, Tan ZG, Pandey M, Srichana T, Pichika MR, Gorain B, et al. A critical review on emerging trends in dry powder inhaler formulation for the treatment of pulmonary aspergillosis. Pharmaceutics. 2020;12(12):1–47.

    Article  CAS  Google Scholar 

  22. Chaurasiya B, Zhao Y. Dry powder for pulmonary delivery : a comprehensive review. Pharmaceutics. 2021;31(13):1–28.

    Google Scholar 

  23. Guo Y, Bera H, Shi C, Zhang L, Cun D, Yang M. Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines. Acta Pharm Sin B. 2021;11(8):2565–84. https://doi.org/10.1016/j.apsb.2021.05.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stegemann S, Faulhammer E, Pinto JT, Paudel A. Focusing on powder processing in dry powder inhalation product development, manufacturing and performance. Int J Pharm. 2022;614(25): 121445.

    Article  CAS  PubMed  Google Scholar 

  25. Xiroudaki S, Schoubben A, Giovagnoli S, Rekkas DM. Dry powder inhalers in the digitalization era: current status and future perspectives. Pharmaceutics. 2021;13(9):1455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ye Y, Ma Y, Zhu J. The future of dry powder inhaled therapy: promising or discouraging for systemic disorders? Int J Pharm. 2022;614:121457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nainwal N. Pulmonary Pharmacology & Therapeutics Treatment of respiratory viral infections through inhalation therapeutics : challenges and opportunities. Pulm Pharmacol Ther. 2022;77(December):102170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mahar R, Chakraborty A, Nainwal N. The influence of carrier type, physical characteristics, and blending techniques on the performance of dry powder inhalers. J Drug Deliv Sci Technol. 2022;76(10):103759.

    Article  CAS  Google Scholar 

  29. Han CS, Kang JH, Kim YJ, Kim DW, Park CW. Inhalable nano-dimpled microspheres containing budesonide-PLGA for improved aerodynamic performance. Int J Nanomedicine. 2022;17:3405–19.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Qin Z, Shi Y, Qiao J, Lin G, Tang B, Li X. CFD simulation of porous microspher particles in the airways of pulmonary fibrosis. Comput Methods Programs Biomed. 2022;225: 107094.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Al Hagbani T, Vishwa B, Abu Lila AS, Alotaibi HF, Khafagy ES, Moin A, et al. Pulmonary targeting of levofloxacin using microsphere-based dry powder inhalation. Pharmaceuticals. 2022;15(5):1–18.

    Google Scholar 

  32. Rosita N, Kalalo T, Miatmoko A, et al. Microspheres for inhalation delivery (characteristics and in vitro release). Int J Med Rev Case Reports. 2022;6(2):24–31.

    Google Scholar 

  33. Mahar R, Chakraborty A, Nainwal N, Bahuguna R, Sajwan M, Jakhmola V. Application of PLGA as a biodegradable and biocompatible polymer for pulmonary delivery of drugs. AAPS PharmSciTech. 2023;18(24):39.

    Article  Google Scholar 

  34. Pan C, Hwang Y, Lin Y, Zeng S, Wang S, Kuo S, et al. Development of polycaprolactone microspheres with controllable and uniform particle size by uniform design experiment in emulsion progress. Sensors Mater. 2019;31(2):311–8.

    Article  CAS  Google Scholar 

  35. Kho K, Cheow WS, Lie RH, Hadinoto K. Aqueous re-dispersibility of spray-dried antibiotic-loaded polycaprolactone nanoparticle aggregates for inhaled anti-bio fi lm therapy. Powder Technol. 2010;203(3):432–9. https://doi.org/10.1016/j.powtec.2010.06.003.

    Article  CAS  Google Scholar 

  36. Dash TK, Konkimalla VB. Poly- є - caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release. 2012;158(1):15–33. https://doi.org/10.1016/j.jconrel.2011.09.064.

    Article  CAS  PubMed  Google Scholar 

  37. Manoukian S, Ohan RAMR. Biodegradable polymeric injectable implants for long-term delivery of contraceptive drugs. J Appl Polym Sci. 2018;135(14):139–48.

    Article  Google Scholar 

  38. Patel P, Raval M, Manvar A, Airao V, Bhatt V, Shah P. Lung cancer targeting efficiency of silibinin loaded poly caprolactone /pluronic F68 inhalable nanoparticles: in vitro and in vivo study. Rai VK, editor. PLoS One. 2022;17(5):e0267257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rezaei FS, Khorshidian A, Beram FM, Derakhshani A, Esmaeili J, Barati A. 3D printed chitosan/polycaprolactone scaffold for lung tissue engineering: hope to be useful for COVID-19 studies. RSC Adv. 2021;11(32):19508–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bulcão RP, Freitas FA, Venturini CG, Dallegrave E, Durgante J, Göethel G, et al. Acute and subchronic toxicity evaluation of poly(ε-Caprolactone) lipid-core nanocapsules in rats. Toxicol Sci. 2013;132(1):162–76.

    Article  PubMed  Google Scholar 

  41. Unal. Paclitaxel-loaded polycaprolactone nanoparticles for lung tumors; formulation, comprehensive in vitro characterization and release kinetic studieS. J Fac Pharm Ankara. 2022;46(3):1009–29.

    Google Scholar 

  42. Patel P, Raval M, Manvar A, Airao V, Bhatt V, Shah P. Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: in vitro and In vivo study. PLoS ONE. 2022;17(5):1–31. https://doi.org/10.1371/journal.pone.0267257.

    Article  CAS  Google Scholar 

  43. El-Sherbiny IM, El-Baz NM, Yacoub MH. Inhaled nano -and microparticles for drug delivery. Glob Cardiol Sci Pract. 2015;2015(1):1–14.

    Google Scholar 

  44. Giovagnoli S, Blasi P, Schoubben A, Rossi C, Ricci M. Preparation of large porous biodegradable microspheres by using a simple double-emulsion method for capreomycin sulfate pulmonary delivery. 2007;333:103–11.

  45. Cocks E, Alpar O, Somavarapu S, Greenleaf D. Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery. Drug Dev Ind Pharm. 2015;41(3):522–8.

    Article  CAS  PubMed  Google Scholar 

  46. Rawat A, Majumder QH, Ahsan F. Inhalable large porous microspheres of low molecular weight heparin: in vitro and in vivo evaluation. J Control Release. 2008;128(3):224–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yang Z, Wang L, Tian L, Zhang X, Huang G. Tadalafil-loaded PLGA microspheres for pulmonary administration : preparation and evaluation. Brazilian J Pharm Sci. 2019;55:1–12.

    Google Scholar 

  48. Tomoda K, Makino K. Effects of lung surfactants on rifampicin release rate from monodisperse rifampicin-loaded PLGA microspheres. Colloids Surfaces B Biointerfaces. 2007;55(1):115–24.

    Article  CAS  PubMed  Google Scholar 

  49. El-Baseir MM, Phipps MA, Kellaway IW. Preparation and subsequent degradation of poly(L-lactic acid) microspheres suitable for aerosolisation: a physico-chemical study. Int J Pharm. 1997;151(2):145–53.

    Article  CAS  Google Scholar 

  50. Feng R, Zhang Z, Li Z, Huang G. Preparation and in vitro evaluation of etoposide-loaded PLGA microspheres for pulmonary drug delivery. Drug Deliv. 2014;21(3):185–92.

    Article  CAS  PubMed  Google Scholar 

  51. Feng T, Tian H, Xu C, Lin L, Xie Z, Lam MHW, et al. Synergistic co-delivery of doxorubicin and paclitaxel by porous PLGA microspheres for pulmonary inhalation treatment. Eur J Pharm Biopharm. 2014;88(3):1086–93. https://doi.org/10.1016/j.ejpb.2014.09.012.

    Article  CAS  PubMed  Google Scholar 

  52. Dimer FA, Ortiz M, Pohlmann AR, Guterres SS. Inhalable resveratrol microparticles produced by vibrational atomization spray drying for treating pulmonary arterial hypertension. J Drug Deliv Sci Technol. 2015;29:152–8. https://doi.org/10.1016/j.jddst.2015.07.008.

    Article  CAS  Google Scholar 

  53. Mali AJ, Rokade A, Kamble R, Pawar A, Bothiraja C. Resveratrol-Loaded Microsponge as a Novel Biodegradable Carrier for Dry Powder Inhaler: A New Strategy in Lung Delivery. Bionanoscience. 2021;11(1):32–43.

    Article  Google Scholar 

  54. Trotta V, Lee W, Loo C, Haghi M, Young PM, Scalia S, et al. In vitro biological activity of resveratrol using a novel inhalable resveratrol spray-dried formulation.Int J Pharm. 2015; https://doi.org/10.1016/j.ijpharm.2015.06.033

  55. Ha ES, Park H, Lee SK, Sim WY, Jeong JS, Kim MS. Equilibrium solubility and modeling of trans-resveratrol in dichloromethane and primary alcohol solvent mixtures at different temperatures. J Mol Liq. 2020;311:113363. https://doi.org/10.1016/j.molliq.2020.113363.

    Article  CAS  Google Scholar 

  56. Zhang S, Campagne C, Salaün F. Preparation of electrosprayed poly(caprolactone) microparticles based on green solvents and related investigations on the effects of solution properties as well as operating parameters. Coatings. 2019;9(2):1–19.

    Article  Google Scholar 

  57. Saharawat A, Deepali Nainwal N. Natural plus synthetic hydrotropic solubilization using response surface methodology to optimize the solid dispersion of hydrochlorothiazide. Comb Chem High Throughput Screen. 2022;25(2):307–23.

    Article  CAS  PubMed  Google Scholar 

  58. Vishwa B, Moin A, Gowda DV, Rizvi SMD, Hegazy WAH, Lila ASA, et al. Pulmonary targeting of inhalable moxifloxacin microspheres for effective management of tuberculosis. Pharmaceutics. 2021;13(1):1–17.

    Article  Google Scholar 

  59. Kim B-K, Lee J, et al. Preperation of resveratrol-loaded poly caprolactone nanoparticles by oil-in-water emulsion solvent evaporation method. Food Sci Biotechnol. 2009;18(1):157–61.

    CAS  Google Scholar 

  60. Huang J, Chen Z, Li Y, Li L, Zhang G. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization. Drug Des Devel Ther. 2017;11:585–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Umon MK, Uzuki MS, Usai AK, Onemochi EY, Erada KT. Novel approach to DPI carrier lactose with mechanofusion process with additives and evaluation by IGC. Chem Pharm Bull. 2006;54(11):1508–14.

    Article  Google Scholar 

  62. Weng J, Tong HHY, Chow SF. In vitro release study of the polymeric drug nanoparticles: development and validation of a novel method. Pharmaceutics. 2020;12(8):1–18.

    Article  Google Scholar 

  63. Rahman MM, Islam MB, Biswas M, Khurshid Alam AHM. In vitro antioxidant and free radical scavenging activity of different parts of Tabebuia pallida growing in Bangladesh. BMC Res Notes. 2015;8(1):1–9.

    Article  CAS  Google Scholar 

  64. Saharan VA, Kataria MK, Ganganagar S, Kharb V, Punjab GM, Choudhury PK. Ordered mixing : mechanism, process and applications in pharmaceutical formulations. Asian J Pharm Sci. 2008;3(6):240–59.

    Google Scholar 

  65. Shah S, Cristopher D, Sharma S, Soniwala M, Chavda J. Inhalable linezolid loaded PLGA nanoparticles for treatment of tuberculosis: design, development and in vitro evaluation. J Drug Deliv Sci Technol. 2020;60:102013. https://doi.org/10.1016/j.jddst.2020.102013.

    Article  CAS  Google Scholar 

  66. Vadakkan MV, Annapoorna K, Sivakumar KC, Mundayoor S, Kumar GSV. Dry powder cationic lipopolymeric nanomicelle inhalation for targeted delivery of antitubercular drug to alveolar macrophage. Int J Nanomedicine. 2013;8:2871–85.

    PubMed  PubMed Central  Google Scholar 

  67. Li W, Chen S, Zhang L, Zhang Y, Yang X, Xie B, et al. Inhalable functional mixed-polymer microspheres to enhance doxorubicin release behavior for lung cancer treatment. Colloids Surfaces B Biointerfaces. 2020;196:111350. https://doi.org/10.1016/j.colsurfb.2020.111350.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang J. An improvement of double emulsion technique for preparing bovine serum albumin-loaded PLGA microspheres. Taylor Fr. 2004;21(7):775–85.

    CAS  Google Scholar 

  69. Bangale GS, Shinde G, KS R, Shirsath N, Marathe D, Jaiswal P, et al. Formulation and optimization of nanoparticale by 3 2 factorial design for colon targeting. Glob J Pharm Pharm Sci. 2022;7(1):1–15. http://juniperpublishers.com/gjpps/GJPPS.MS.ID.555702.php

  70. Shirsath N, Marathe D, Jaiswal P, Zawar L. A 32 factorial design approach for formulation and optimization of azilsartan medoxomil nanosuspension for solubility enhancement. Indian J Pharm Educ Res. 2022;56(2):S365–73.

    Article  CAS  Google Scholar 

  71. Lee KH, Khan FN, Cosby L, Yang G, Winter JO. Polymer concentration maximizes encapsulation efficiency in electrohydrodynamic mixing nanoprecipitation. Front Nanotechnol. 2021;3(December):1–14.

    Google Scholar 

  72. Huang W, Tsui CP, Tang CY, Gu L. Effects of compositional tailoring on drug delivery behaviours of silica xerogel/polymer core-shell composite nanoparticles. Sci Rep. 2018;8(1):1–13. https://doi.org/10.1038/s41598-018-31070-9.

    Article  CAS  Google Scholar 

  73. Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: a co-surfactant study. Asian J Pharm Sci. 2016;11(3):404–16. https://doi.org/10.1016/j.ajps.2015.09.004.

    Article  Google Scholar 

  74. Turk CTS, Oz UC, Serim TM, Hascicek C. Formulation and optimization of nonionic surfactants emulsified nimesulide-loaded PLGA-based nanoparticles by design of experiments. AAPS PharmSciTech. 2014;15(1):161–76.

    Article  CAS  PubMed  Google Scholar 

  75. Iftikhar SY, Iqbal FM, Hassan W, Nasir B, Sarwar AR. Desirability combined response surface methodology approach for optimization of prednisolone acetate loaded chitosan nanoparticles and in-vitro assessment. Mater Res Express. 2020;7(11):115004.

    Article  CAS  Google Scholar 

  76. Mendes JBE, et al. PHBV/PCL microparticles for controlled release of resveratrol: physicochemical characterization, antioxidant potential, and effect on hemolysis of human erythrocytes. Sci World J. 2012;12:1–13.

    Article  Google Scholar 

  77. Makino K, Yamamoto N, Higuchi K, Harada N, Ohshima H, Terada H. Phagocytic uptake of polystyrene microspheres by alveolar macrophages: effects of the size and surface properties of the microspheres. Colloids Surfaces B Biointerfaces. 2003;27(1):33–9.

    Article  CAS  Google Scholar 

  78. Champion JA, Walker A, Mitragotri S. Role of particle size in phagocytosis of polymeric microspheres. Pharm Res. 2008;25(8):1815–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Han CS, Kang JH, Kim YJ, Kim DW, Park CW. Inhalable nano-dimpled microspheres containing budesonide-PLGA for improved aerodynamic performance. Int J Nanomedicine. 2022;17(July):3405–19.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Carletto B, Berton J, Ferreira TN, Dalmolin LF, Paludo KS, Mainardes RM, et al. Resveratrol-loaded nanocapsules inhibit murine melanoma tumor growth. Colloids Surf B Biointerfaces. 2016;144(March 2021):65–72.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang H, Xu J. Enhanced oral bioavailability of salmeterol by loaded PLGA microspheres: preparation, in vitro, and in vivo evaluation. Drug Deliv. 2016;23(1):248–53.

    Article  CAS  PubMed  Google Scholar 

  82. Dhakar RC. From formulation variables to drug entrapment efficiency of microspheres : a technical review. J drug Deliv Ther. 2016;2(6):128–33.

    Google Scholar 

  83. Kundawala A, Patel V, Patel H, Choudhary D. Preparation, in vitro characterization, and in vivo pharmacokinetic evaluation of respirable porous microparticles containing rifampicin. Sci Pharm. 2014;82(3):665–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Paarakh MP, Jose PANI, Setty CM, Peter GV. Release kinetics – concepts and applications. Int J Pharm Res Technol. 2019;8(1):12–20.

    Google Scholar 

  85. Campisi A, Acquaviva R, Raciti G, Duro A, Rizzo M, Santagati NA. Antioxidant activities of Solanum nigrum L. Leaf extracts determined in in vitro cellular models. Foods. 2019;8(2):1–12.

    Article  Google Scholar 

  86. Baliyan S, Mukherjee R, Priyadarshini A, Vibhuti A, Gupta A, Pandey RP, et al. Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules. 2022;27(4):1326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Menon M, Naik I, Rajawat GS, Nagarsenker M, Krishnaprasad K. Nebulized glycopyrronium and formoterol, budesonide aerosol aerodynamic assessment with vibrating mesh and compressor air nebulizer: Anderson Cascade Impactor Study. J Drug Deliv Ther. 2019;9(6):79–82.

    Article  CAS  Google Scholar 

  88. Chow MYT, Tai W, Chang RYK, Chan HK, Kwok PCL. In vitro-in vivo correlation of cascade impactor data for orally inhaled pharmaceutical aerosols. Adv Drug Deliv Rev. 2021;177:113952. https://doi.org/10.1016/j.addr.2021.113952.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Balawala, Dehradun, 248161, India

    Riya Mahar

  2. School of Pharmaceutical Sciences, Himgiri Zee University, Dehradun, Sherpur, 248197, Uttarakhand, India

    Riya Mahar

  3. Alkem Health Science Private Limited, Samardung, 737116, Sikkim, India

    Arpita Chakraborty

  4. Uttaranchal Institute of Pharmaceutical Sciences and Technology, Uttaranchal University, Premnagar, Dehradun, Uttarakhand, 248007, India

    Nidhi Nainwal

Authors
  1. Riya Mahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arpita Chakraborty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nidhi Nainwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The research work of this manuscript was done by Riya Mahar. Dr. Nidhi Nainwal guided Ms. Riya Mahar throughout the research work and in drafting the manuscript. Ms. Arpita Chakraborty helped Riya Mahar in the formulation and evaluation work. All the authors of this manuscript contributed in direct or indirect method for publication of this work.

Corresponding author

Correspondence to Nidhi Nainwal.

Ethics declarations

Ethics Approval

Not applicable.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahar, R., Chakraborty, A. & Nainwal, N. Formulation of Resveratrol-Loaded Polycaprolactone Inhalable Microspheres Using Tween 80 as an Emulsifier: Factorial Design and Optimization. AAPS PharmSciTech 24, 131 (2023). https://doi.org/10.1208/s12249-023-02587-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-023-02587-8

Keywords

Search

Navigation