Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis

Vinayak Kabra; Swaroop Lahoti

Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis

Abstract

Cystic fibrosis is the most common autosomal recessive disease that shortens life expectancy. According to studies, approximately 60 to 70% of adult patients are infected with P. aeruginosa. The current work explores the possibility of preparing microparticles using the spray-drying and freeze-drying methods and comparing the results obtained. A combination of ivacaftor and ciprofloxacin was loaded in microparticles of bovine serum albumin with L-leucine by the spray drying and freeze drying approaches to generate microparticles that could be delivered via a dry powder inhaler. The spray-dried microparticles had a particle size of 1.6 ± 0.04 µm with a polydispersity ratio of 0.33. They had a zeta potential of -27.3 ± 1.1 mV. The mass median aerodynamic diameter of the spray-dried microparticles was 3.74 ± 0.08 μm. The freeze-dried microparticles had a particle size of 0.8175 ± 5.6 µm with a polydispersity ratio of 0.33. They had a zeta potential of -23.3 ± 1.1 mV. The mass median aerodynamic diameter of the microparticles was 3.75 ± 0.07 μm. The microparticles produced by the spray-drying process were found to have better aerosol performance.

Keywords

References

[1] Kiedrowski MR, Bomberger JM. Viral-bacterial co-infections in the cystic fibrosis respiratory tract. Front Immunol. 2018; 9: 3067. https://doi.org/10.3389/fimmu.2018.03067.
[2] Crull MR, Somayaji R, Ramos KJ, Caldwell E, Mayer-Hamblett N, Aitken ML, Nichols DP, Rowhani-Rahbar A, Goss CH. Changing rates of chronic Pseudomonas aeruginosa infections in cystic fibrosis: A population-based cohort study. Clin Infect Dis. 2018; 67(7): 1089–1095. https://doi.org/10.1093/cid/ciy215.
[3] Acosta N, Waddell B, Heirali A, Somayaji R, Surette MG, Workentine ML, Rabin HR, Parkins MD. Cystic fibrosis patients infected with epidemic Pseudomonas aeruginosa strains have unique microbial communities. Front Cell Infect Microbiol. 2020; 10: 173. https://doi.org/10.3389/fcimb.2020.00173.
[4] Yu S, Pu X, Ahmed MU, Yu HH, Mutukuri TT, Li J, Zhou QT. Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa. Int J Pharm. 2021; 610: 121160. https://doi.org/10.1016/j.ijpharm.2021.121160.
[5] Yakubu SI, Assi KH, Chrystyn H. Aerodynamic dose emission characteristics of dry powder inhalers using an Andersen Cascade Impactor with a mixing inlet: the influence of flow and volume. Int J Pharm. 2013; 455(1–2): 213–218. https://doi.org/10.1016/j.ijpharm.2013.07.036.
[6] Chaurasiya B, Zhao YY. Dry powder for pulmonary delivery: A comprehensive review. Pharmaceutics. 2021; 13(1): 31. https://doi.org/10.3390/pharmaceutics13010031.
[7] Aramwit P. Introduction to biomaterials for wound healing. In: Ågren MS, editor. Wound Healing Biomaterials. Woodhead Publishing; 2016. p. 3–38. https://doi.org/10.1016/B978-1-78242-456-7.00001-5.
[8] Choi SH, Byeon HJ, Choi JS, Thao L, Kim I, Lee ES, Shin BS, Lee KC, Youn YS. Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer. J Control Release. 2015; 197: 199–207. https://doi.org/10.1016/j.jconrel.2014.11.008.

[9] Yu Z, Yu M, Zhang Z, Hong G, Xiong Q. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear. Nanoscale Res Lett. 2014; 9(1): 343. https://doi.org/10.1186/1556-276x-9-343.
[10] Wang W, Lei Y, Sui H, Zhang W, Zhu R, Feng J, Wang H. Fabrication and evaluation of nanoparticle-assembled BSA microparticles for enhanced liver delivery of glycyrrhetinic acid. Artif Cells Nanomed Biotechnol. 2017; 45(4): 740–747. https://doi.org/10.1080/21691401.2016.1193024.
[11] Lee G. Spray-Drying of Proteins. In: Carpenter JF, Manning MC, editors. Rational Design of Stable Protein Formulations. Boston, MA: Springer US; 2002. p. 135–158. https://doi.org/10.1007/978-1-4615-0557-0_6.
[12] Pedrozo RC, Antônio E, Khalil NM, Mainardes RM. Bovine serum albumin-based nanoparticles containing the flavonoid rutin produced by nano spray drying. Braz J Pharm Sci. 2020; 56: e17692. http://dx.doi.org/10.1590/s2175-97902019000317692.
[13] Nettey H, Haswani D, Oettinger CW, D’Souza MJ. Formulation and testing of vancomycin loaded albumin microspheres prepared by spray-drying. J Microencapsul. 2006; 23(6): 632–642. https://doi.org/10.1080/02652040600776564.
[14] Mangal S, Meiser F, Tan G, Gengenbach T, Denman J, Rowles MR, Larson I, Morton DAV. Relationship between surface concentration of l-leucine and bulk powder properties in spray dried formulations. Eur J Pharm Biopharm. 2015; 94: 160–169. https://doi.org/10.1016/j.ejpb.2015.04.035.
[15] Thiyagarajan D, Huck B, Nothdurft B, et al. Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals. Drug Deliv Transl Res. 2021; 11(4): 1766–1778. https://doi.org/10.1007/s13346-021-01011-7.
[16] Xu Y, Harinck L, Lokras AG, et al. Leucine improves the aerosol performance of dry powder inhaler formulations of siRNA-loaded nanoparticles. Int J Pharm. 2022; 621: 121758. https://doi.org/10.1016/j.ijpharm.2022.121758.
[17] Party P, Kókai D, Burián K, Nagy A, Hopp B, Ambrus R. Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: In vitro aerodynamic and cell line measurements. Eur J Pharm Sci. 2022; 176: 106247. https://doi.org/10.1016/j.ejps.2022.106247.
[18] Wang X, Wan W, Lu J, Quan G, Pan X, Liu P. Effects of L-leucine on the properties of spray-dried swellable microparticles with wrinkled surfaces for inhalation therapy of pulmonary fibrosis. Int J Pharm. 2021; 610: 121223. https://doi.org/10.1016/j.ijpharm.2021.121223.
[19] Momin MAM, Rangnekar B, Sinha S, Cheung CY, Cook GM, Das SC. Inhalable dry powder of bedaquiline for pulmonary tuberculosis: In vitro physicochemical characterization, antimicrobial activity and safety studies. Pharmaceutics. 2019; 11(10): 502. https://doi.org/10.3390/pharmaceutics11100502.
[20] Lu P, Xing Y, Peng H, Liu Z, Zhou Q (Tony), Xue Z, Ma Z, Kebebe D, Zhang B, Liu H. Physicochemical and pharmacokinetic evaluation of spray-dried coformulation of Salvia miltiorrhiza polyphenolic acid and L-Leucine with improved bioavailability. J Aerosol Med Pulm Drug Deliv. 2020; 33(2): 73–82. https://doi.org/10.1089/jamp.2019.1538.
[21] Alhajj N, O’Reilly NJ, Cathcart H. Leucine as an excipient in spray dried powder for inhalation. Drug Discov Today. 2021; 26(10): 2384–2396. https://doi.org/10.1016/j.drudis.2021.04.009.
[22] Guo Y, Baldelli A, Singh A, Fathordoobady F, Kitts D, Pratap-Singh A. Production of high loading insulin nanoparticles suitable for oral delivery by spray drying and freeze drying techniques. Sci Rep. 2022; 12(1): 9949. https://doi.org/10.1038/s41598-022-13092-6.
[23] Baldelli A, Cidem A, Guo Y, Ong HX, Singh A, Traini D, Pratap-Singh A. Spray freeze drying for protein encapsulation: Impact of the formulation to morphology and stability. Dry Technol. 2022; 41(1): 1–14. https://doi.org/10.1080/07373937.2022.2089162.
[24] Baysan U, Zungur Bastıoğlu A, Coşkun NÖ, Konuk Takma D, Ülkeryıldız Balçık E, Sahin-Nadeem H, Koc M. The effect of coating material combination and encapsulation method on propolis powder properties. Powder Technol. 2021; 384: 332–341. https://doi.org/10.1016/j.powtec.2021.02.018.
[25] Singh SK, Vuddanda PR, Singh S, Srivastava AK. A comparison between use of spray and freeze drying techniques for preparation of solid self-microemulsifying formulation of valsartan and in vitro and in vivo evaluation. Biomed Res Int. 2013; 2013: e909045. https://doi.org/10.1155/2013/909045.
[26] Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res. 2008; 25(5): 999–1022. https://doi.org/10.1007/s11095-007-9475-1.
[27] Zheng Z, Leung SSY, Gupta R. Flow and particle modelling of dry powder inhalers: Methodologies, recent development and emerging applications. Pharmaceutics. 2021; 13(2): 189. https://doi.org/10.3390/pharmaceutics13020189.
[28] Courrier HM, Butz N, Vandamme TF. Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst. 2002; 19(4–5): 425–498. https://doi.org/10.1615/critrevtherdrugcarriersyst.v19.i45.40.
[29] Takechi-Haraya Y, Ohgita T, Demizu Y, Saito H, Izutsu K, Sakai-Kato K. Current status and challenges of analytical methods for evaluation of size and surface modification of nanoparticle-based drug formulations. AAPS PharmSciTech. 2022; 23(5): 150. https://doi.org/10.1208/s12249-022-02303-y.
[30] Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol. 2011; 697: 63–70. https://doi.org/10.1007/978-1-60327-198-1_6.
[31] Tarhini M, Pizzoccaro A, Benlyamani I, Rebaud C, Greige-Gerges H, Fessi H, Elaissari A, Bentaher A. Human serum albumin nanoparticles as nanovector carriers for proteins: Application to the antibacterial proteins “neutrophil elastase” and “secretory leukocyte protease inhibitor.” Int J Pharm. 2020; 579: 119150. https://doi.org/10.1016/j.ijpharm.2020.119150.
[32] Edsman K, Hägerström H. Pharmaceutical applications of mucoadhesion for the non-oral routes. J Pharm Pharmacol. 2005; 57(1): 3–22. https://doi.org/10.1211/0022357055227.
[33] Dünnhaupt S, Kammona O, Waldner C, Kiparissides C, Bernkop-Schnürch A. Nano-carrier systems: Strategies to overcome the mucus gel barrier. Eur J Pharm Biopharm. 2015; 96: 447–453. https://doi.org/10.1016/j.ejpb.2015.01.022.
[34] Luo J, Jang HD, Sun T, Xiao L, He Z, Katsoulidis AP, Kanatzidis MG, Gibson JM, Huang J. Compression and aggregation-resistant particles of crumpled soft sheets. ACS Nano. 2011; 5(11): 8943–8949. https://doi.org/10.1021/nn203115u.
[35] Padhi BK, Chougule MB, Misra A. Aerosol performance of large respirable particles of amikacin sulfate produced by spray and freeze drying techniques. Curr Drug Deliv. 2009; 6(1): 8–16. https://doi.org/10.2174/156720109787048267.
[36] He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying. Int J Pharm. 1999; 187(1): 53–65. https://doi.org/10.1016/s0378-5173(99)00125-8.
[37] Busto MD, González-Temiño Y, Albillos SM, Ramos-Gómez S, Pilar-Izquierdo MC, Palacios D, Ortega N. Microencapsulation of a commercial food-grade protease by spray drying in cross-linked chitosan particles. Foods. 2022; 11(14): 2077. https://doi.org/10.3390/foods11142077.
[38] Both EM, Boom RM, Schutyser MAI. Particle morphology and powder properties during spray drying of maltodextrin and whey protein mixtures. Powder Technol. 2020; 363: 519–524. https://doi.org/10.1016/j.powtec.2020.01.001.
[39] Torge A, Pavone G, Jurisic M, Lima-Engelmann K, Schneider M. A comparison of spherical and cylindrical microparticles composed of nanoparticles for pulmonary application. Aerosol Sci Technol. 2019; 53(1): 53–62. https://doi.org/10.1080/02786826.2018.1542484.
[40] Wolska E. Fine powder of lipid microparticles – spray drying process development and optimization. J Drug Deliv Sci Technol. 2021; 64: 102640. https://doi.org/10.1016/j.jddst.2021.102640.
[41] Nangare S, Dugam S, Patil P, Tade R, Jadhav N. Silk industry waste protein: isolation, purification and fabrication of electrospun silk protein nanofibers as a possible nanocarrier for floating drug delivery. Nanotechnol. 2020; 32(3): 035101. https://doi.org/10.1088/1361-6528/abb8a9.
[42] Radivojev S, Luschin-Ebengreuth G, Pinto JT, Laggner P, Cavecchi A, Cesari N, Cella M, Melli F, Paudel A, Fröhlich E. Impact of simulated lung fluid components on the solubility of inhaled drugs and predicted in vivo performance. Int J Pharm. 2021; 606: 120893. https://doi.org/10.1016/j.ijpharm.2021.120893.
[43] Herrera LC, Tesoriero MV, Hermida LG. In vitro release testing of PLGA microspheres with Franz Diffusion cells. Dissol Technol. 2012; 19(2): 6–11.
[44] Schober P, Vetter TR. Two-sample unpaired t tests in medical research. Anesth Analg. 2019; 129(4): 911. https://doi.org/10.1213/ane.0000000000004373.

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Vinayak Kabra This is me
0000-0002-1520-0457
India

Swaroop Lahoti ^* This is me
0000-0002-8730-719X
India

Publication Date

June 28, 2025

Submission Date

January 19, 2023

Acceptance Date

May 25, 2023

Published in Issue

Year 2023 Volume: 27 Number: 6

IZ

https://izlik.org/JA57WK96AK

Cite

RIS / Bibtex

APA

Kabra, V., & Lahoti, S. (2025). Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis. Journal of Research in Pharmacy, 27(6), 2443-2451. https://izlik.org/JA57WK96AK

AMA

1.Kabra V, Lahoti S. Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis. J. Res. Pharm. 2025;27(6):2443-2451. https://izlik.org/JA57WK96AK

Chicago

Kabra, Vinayak, and Swaroop Lahoti. 2025. “Comparison Between Spray Drying and Freeze Drying Techniques for the Preparation of Microparticles for Delivery via a Dry Powder Inhaler to Treat Cystic Fibrosis”. Journal of Research in Pharmacy 27 (6): 2443-51. https://izlik.org/JA57WK96AK.

EndNote

Kabra V, Lahoti S (July 1, 2025) Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis. Journal of Research in Pharmacy 27 6 2443–2451.

IEEE

[1]V. Kabra and S. Lahoti, “Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis”, J. Res. Pharm., vol. 27, no. 6, pp. 2443–2451, July 2025, [Online]. Available: https://izlik.org/JA57WK96AK

ISNAD

Kabra, Vinayak - Lahoti, Swaroop. “Comparison Between Spray Drying and Freeze Drying Techniques for the Preparation of Microparticles for Delivery via a Dry Powder Inhaler to Treat Cystic Fibrosis”. Journal of Research in Pharmacy 27/6 (July 1, 2025): 2443-2451. https://izlik.org/JA57WK96AK.

JAMA

1.Kabra V, Lahoti S. Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis. J. Res. Pharm. 2025;27:2443–2451.

MLA

Kabra, Vinayak, and Swaroop Lahoti. “Comparison Between Spray Drying and Freeze Drying Techniques for the Preparation of Microparticles for Delivery via a Dry Powder Inhaler to Treat Cystic Fibrosis”. Journal of Research in Pharmacy, vol. 27, no. 6, July 2025, pp. 2443-51, https://izlik.org/JA57WK96AK.

Vancouver

1.Vinayak Kabra, Swaroop Lahoti. Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(6):2443-51. Available from: https://izlik.org/JA57WK96AK