Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods

Yagmur Akdag; Tuğba Gülsün İnal; Nihan Izat; Levent Öner; Selma Şahin

Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods

Abstract

This study aimed to design and characterize an inhalable dry powder of mometasone furoate monohydrate (MFM) combined with the formoterol fumarate dihydrate (FFD). Homogenization in water and spray drying processes were used to prepare the dry powders for inhalation. The physicochemical characteristics of the dry powders were evaluated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The particle size distribution, content uniformity, solid behavior and aerodynamic properties of DPI were also determined. After the micronization process, the particle sizes of the raw materials significantly decreased. SEM images implied that FFD covered the MFM surface during the spray drying step, and uniform particles were produced. X-ray and DSC results demonstrated that MFM did not show any change in crystal structure after homogenization and spray drying processes. DSC analysis of DPI formulation exhibited that the same melting point of MFM was observed when the drugs were spray dried. FT-IR spectra exhibited the characteristic peaks for MFM in DPI formulation. Content uniformity results showed that the developed production method is suitable for manufacturing uniform formulations. According to angle of repose, Hausner ratio and Carr’s index results, DPI formulation has preferable flow properties. In addition, emitted dose, mass median aerodynamic diameter, fine particle fraction showed that the DPI formulation could ensure drug delivery to the alveoli. This study showed that the combination of homogenization and spray drying methods is suitable to obtain a DPI formulation containing MFM and FFD with a particle size less than 5 µm to reach alveoli.

Keywords

References

[1] Cohn L, Elias JA, Chupp GL. Asthma: Mechanisms of Disease Persistence and Progression. Annu Rev Immunol. 2004;22(1):789-815. [CrossRef]
[2] Wang E, Wechsler ME, Tran TN, Heaney LG, Jones RC, Menzies-Gow AN, Busby J, Jackson DJ, Pfeffer PE, Rhee CK, Cho YS, Canonica GW, Heffler E, Gibson PG, Hew M, Peters M, Harvey ES, Alacqua M, Zangrilli J, Bulathsinhala L, Carter VA, Chaudhry I, Eleangovan N, Hosseini N, Murray RB, Price DB. Characterization of Severe Asthma Worldwide: Data From the International Severe Asthma Registry. Chest. 2020;157(4):790-804. [CrossRef]
[3] Enilari O, Sinha S. The Global Impact of Asthma in Adult Populations. Ann Glob Health. 2019;85(1):2. [CrossRef]
[4] Groneberg DA, Witt C, Wagner U, Chung KF, Fischer A. Fundamentals of pulmonary drug delivery. Respir Med. 2003;97(4):382-7. [CrossRef]
[5] Blau H, Mussaffi H, Mei Zahav M, Prais D, Livne M, Czitron BM, Cohen HA. Microbial contamination of nebulizers in the home treatment of cystic fibrosis. Child: Care Health Dev. 2007;33(4):491-495. [CrossRef]
[6] Cohen HA, Cohen Z, Pomeranz AS, Czitron B, Kahan E. Bacterial contamination of spacer devices used by asthmatic children. J Asthma. 2005;42(3):169-172. [CrossRef]
[7] de Vries TW, Rienstra SR, van der Vorm ER. Bacterial contamination of inhalation chambers: results of a pilot study. J Aerosol Med Pulm Drug Deliv. 2004;17(4):354-356. [CrossRef]
[8] Cipolla D, Chan HK, Schuster J, Farina D. Personalizing aerosol medicine: development of delivery systems tailored to the individual. Ther Deliv. 2010;1(5):667-682. [CrossRef]

[9] Geller DE, Konstan MW, Smith J, Noonberg SB, Conrad C. Novel tobramycin inhalation powder in cystic fibrosis subjects: Pharmacokinetics and safety. Pediatr Pulmonol. 2007;42(4):307-313. [CrossRef]
[10] Konstan MW, Flume PA, Kappler M, Chiron R, Higgins M, Brockhaus F, Zhang J, Angyalosi G, He E, Geller HE. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros. 2011;10(1):54-61. [CrossRef]
[11] Smith IJ, Parry-Billings M. The inhalers of the future? A review of dry powder devices on the market today. Pulm Pharmacol Ther. 2003;16(2):79-95. [CrossRef]
[12] Telko MJ, Hickey AJ. Dry powder inhaler formulation. Respir Care. 2005;50(9):1209-1227.
[13] Akapo SO, Asif M. Validation of a RP-HPLC method for the assay of formoterol and its related substances in formoterol fumarate dihydrate drug substance. J Pharm Biomed Anal. 2003;33(5):935-945. [CrossRef]
[14] Sharpe M, Jarvis B. Inhaled mometasone furoate: a review of its use in adults and adolescents with persistent asthma. Drugs. 2001;61(9):1325-1350. [CrossRef]
[15] Meenach SA, Anderson KW, Hilt JZ, McGarry RC, Mansour HM. High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: Physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AAPS Pharm Sci Tech. 2014;15(6):1574-1587. [CrossRef]
[16] Mohapatra M, Mishra AK. 1-Naphthol as a sensitive fluorescent molecular probe for monitoring the interaction of submicellar concentration of bile salt with a bilayer membrane of DPPC, a lung surfactant. J Phys Chem B 2010;114(46):14934-14940. [CrossRef]
[17] Santos D, Maurício AC, Sencadas V, Santos JD, Fernandes MH, Gomes PS. Spray drying: an overview. Pignatello, R(Comp) Biomaterials-Physics and Chemistry-New Edition InTech UK. 2018; 9-35. [CrossRef]
[18] Pilcer G, Vanderbist F, Amighi K. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery. Int J Pharm. 2009;365(1-2):162-169. [CrossRef]
[19] Akdag Cayli Y, Sahin S, Buttini F, Balducci AG, Montanari S, Vural I, Öner L. Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients. Drug Dev Ind Pharm. 2017:1-12. [CrossRef]
[20] Chen XS, Carillo M, Haltiwanger RC, Bradley P. Solid state characterization of mometasone furoate anhydrous and monohydrate forms. J Pharm Sci. 2005;94(11):2496-2509. [CrossRef]
[21] Tajber L, Corrigan DO, Corrigan OI, Healy AM. Spray drying of budesonide, formoterol fumarate and their composites—I. Physicochemical characterisation. Int J Pharm. 2009;367(1):79-85. [CrossRef]
[22] Carvalho SR, Watts AB, Peters JI, Liu S, Hengsawas S, Escotet-Espinoza MS, Wiiliams 3rd OR. Characterization and pharmacokinetic analysis of crystalline versus amorphous rapamycin dry powder via pulmonary administration in rats. Eur J Pharm Biopharm. 2014;88(1):136-147. [CrossRef]
[23] Graeser KA, Strachan CJ, Patterson JE, Gordon KC, Rades T. Physicochemical properties and stability of two differently prepared amorphous forms of simvastatin. Cryst Growth Des. 2008;8(1):128-135. [CrossRef]
[24] USP 30-NF 25 Powder Flow (2005), p. 643. [CrossRef]
[25] Patel K, Bothiraja C, Mali A, Kamble R. Investigation of sorafenib tosylate loaded liposomal dry powder inhaler for the treatment of non-small cell lung cancer. Part Sci Technol. 2021:990-999. [CrossRef]
[26] Pham D-D, Fattal E, Ghermani N, Guiblin N, Tsapis N. Formulation of pyrazinamide-loaded large porous particles for the pulmonary route: avoiding crystal growth using excipients. Int J Pharm. 2013;454(2):668-677. [CrossRef]
[27] Li X, Gu L, Xu Y, Wang Y. Preparation of fenofibrate nanosuspension and study of its pharmacokinetic behavior in rats. Drug Dev Ind Pharm. 2009;35(7):827-833. [CrossRef]
[28] Khan I, Apostolou M, Bnyan R, Houacine C, Elhissi A, Yousaf SS. Paclitaxel-loaded micro or nano transfersome formulation into novel tablets for pulmonary drug delivery via nebulization. Int J Pharm. 2020;575:118919. [CrossRef]
[29] Chaurasiya B, Huang L, Du Y, Tang B, Qiu Z, Zhou L, Tu J, Sun C. Size-based anti-tumoral effect of paclitaxel loaded albumin microparticle dry powders for inhalation to treat metastatic lung cancer in a mouse model. Int J Pharm. 2018;542(1-2):90-99. [CrossRef]
[30] Gujarati PZ, Thula KC, Maheshwari DG. Stability indicating HPLC method for simultaneous estimation of mometasone furoate and formoterol fumarate in combined dosage form. Pharmacophore. 2014;5(2):219. [CrossRef]

Details

Primary Language

English

Subjects

Pharmaceutical Biotechnology

Journal Section

Research Article

Authors

Yagmur Akdag
0000-0003-4139-9815
Türkiye

Tuğba Gülsün İnal
0000-0001-9359-276X
Türkiye

Nihan Izat
0000-0001-7378-9100
Türkiye

Levent Öner
0000-0002-6510-7680
Türkiye

Selma Şahin
0000-0001-5736-5906
Türkiye

Publication Date

June 28, 2025

Submission Date

July 13, 2021

Acceptance Date

December 30, 2021

Published in Issue

Year 2022 Volume: 26 Number: 2

IZ

https://izlik.org/JA56KU83TP

Cite

RIS / Bibtex

APA

Akdag, Y., Gülsün İnal, T., Izat, N., Öner, L., & Şahin, S. (2025). Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods. Journal of Research in Pharmacy, 26(2), 383-396. https://izlik.org/JA56KU83TP

AMA

1.Akdag Y, Gülsün İnal T, Izat N, Öner L, Şahin S. Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods. J. Res. Pharm. 2025;26(2):383-396. https://izlik.org/JA56KU83TP

Chicago

Akdag, Yagmur, Tuğba Gülsün İnal, Nihan Izat, Levent Öner, and Selma Şahin. 2025. “Formulation and Characterization of Mometasone Furoate and Formoterol Fumarate Containing Dry Powder Inhaler by Spray Drying and Homogenization Methods”. Journal of Research in Pharmacy 26 (2): 383-96. https://izlik.org/JA56KU83TP.

EndNote

Akdag Y, Gülsün İnal T, Izat N, Öner L, Şahin S (June 1, 2025) Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods. Journal of Research in Pharmacy 26 2 383–396.

IEEE

[1]Y. Akdag, T. Gülsün İnal, N. Izat, L. Öner, and S. Şahin, “Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods”, J. Res. Pharm., vol. 26, no. 2, pp. 383–396, June 2025, [Online]. Available: https://izlik.org/JA56KU83TP

ISNAD

Akdag, Yagmur - Gülsün İnal, Tuğba - Izat, Nihan - Öner, Levent - Şahin, Selma. “Formulation and Characterization of Mometasone Furoate and Formoterol Fumarate Containing Dry Powder Inhaler by Spray Drying and Homogenization Methods”. Journal of Research in Pharmacy 26/2 (June 1, 2025): 383-396. https://izlik.org/JA56KU83TP.

JAMA

1.Akdag Y, Gülsün İnal T, Izat N, Öner L, Şahin S. Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods. J. Res. Pharm. 2025;26:383–396.

MLA

Akdag, Yagmur, et al. “Formulation and Characterization of Mometasone Furoate and Formoterol Fumarate Containing Dry Powder Inhaler by Spray Drying and Homogenization Methods”. Journal of Research in Pharmacy, vol. 26, no. 2, June 2025, pp. 383-96, https://izlik.org/JA56KU83TP.

Vancouver

1.Yagmur Akdag, Tuğba Gülsün İnal, Nihan Izat, Levent Öner, Selma Şahin. Formulation and characterization of mometasone furoate and formoterol fumarate containing dry powder inhaler by spray drying and homogenization methods. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(2):383-96. Available from: https://izlik.org/JA56KU83TP