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Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis.
Drug Dev Ind Pharm. 2019 Aug; 45(8):1321-1331.DD

Abstract

This study aimed to develop a combination dry powder formulation of ethionamide and moxifloxacin HCl as this combination is synergistic against drug-resistant Mycobacterium tuberculosis (Mtb). L-leucine (20% w/w) was added in the formulations to maximize the process yield. Moxifloxacin HCl and/or ethionamide powders with/without L-leucine were produced using a Buchi Mini Spray-dryer. A next generation impactor was used to determine the in vitro aerosolization efficiency. The powders were also characterized for other physicochemical properties and cytotoxicity. All the spray-dried powders were within the aerodynamic size range of <5.0 µm except ethionamide-only powder (6.0 µm). The combination powders with L-leucine aerosolized better (% fine particle fraction (FPF): 61.3 and 61.1 for ethionamide and moxifloxacin, respectively) than ethionamide-only (%FPF: 9.0) and moxifloxacin-only (%FPF: 30.8) powders. The combination powder particles were collapsed with wrinkled surfaces whereas moxifloxacin-only powders were spherical and smooth and ethionamide-only powders were angular-shaped flakes. The combination powders had low water content (<2.0%). All the powders were physically stable at 15% RH and 25 ± 2 °C during 1-month storage and tolerated by bronchial epithelial cell-lines up to 100 µg/ml. The improved aerosolization of the combination formulation may be helpful for the effective treatment of drug-resistant tuberculosis. Further studies are required to understand the mechanisms for improved aerosolization and test the synergistic activity of the combination powder.

Authors+Show Affiliations

a School of Pharmacy, University of Otago , Dunedin , New Zealand.a School of Pharmacy, University of Otago , Dunedin , New Zealand.a School of Pharmacy, University of Otago , Dunedin , New Zealand.a School of Pharmacy, University of Otago , Dunedin , New Zealand.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31014129

Citation

Momin, Mohammad A M., et al. "Carrier-free Combination Dry Powder Inhaler Formulation of Ethionamide and Moxifloxacin for Treating Drug-resistant Tuberculosis." Drug Development and Industrial Pharmacy, vol. 45, no. 8, 2019, pp. 1321-1331.
Momin MAM, Sinha S, Tucker IG, et al. Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis. Drug Dev Ind Pharm. 2019;45(8):1321-1331.
Momin, M. A. M., Sinha, S., Tucker, I. G., & Das, S. C. (2019). Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis. Drug Development and Industrial Pharmacy, 45(8), 1321-1331. https://doi.org/10.1080/03639045.2019.1609494
Momin MAM, et al. Carrier-free Combination Dry Powder Inhaler Formulation of Ethionamide and Moxifloxacin for Treating Drug-resistant Tuberculosis. Drug Dev Ind Pharm. 2019;45(8):1321-1331. PubMed PMID: 31014129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis. AU - Momin,Mohammad A M, AU - Sinha,Shubhra, AU - Tucker,Ian G, AU - Das,Shyamal C, Y1 - 2019/05/21/ PY - 2019/4/25/pubmed PY - 2019/12/18/medline PY - 2019/4/25/entrez KW - Carrier-free KW - combination KW - drug-resistant KW - dry powder inhaler KW - spray-drying KW - tuberculosis SP - 1321 EP - 1331 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 45 IS - 8 N2 - This study aimed to develop a combination dry powder formulation of ethionamide and moxifloxacin HCl as this combination is synergistic against drug-resistant Mycobacterium tuberculosis (Mtb). L-leucine (20% w/w) was added in the formulations to maximize the process yield. Moxifloxacin HCl and/or ethionamide powders with/without L-leucine were produced using a Buchi Mini Spray-dryer. A next generation impactor was used to determine the in vitro aerosolization efficiency. The powders were also characterized for other physicochemical properties and cytotoxicity. All the spray-dried powders were within the aerodynamic size range of <5.0 µm except ethionamide-only powder (6.0 µm). The combination powders with L-leucine aerosolized better (% fine particle fraction (FPF): 61.3 and 61.1 for ethionamide and moxifloxacin, respectively) than ethionamide-only (%FPF: 9.0) and moxifloxacin-only (%FPF: 30.8) powders. The combination powder particles were collapsed with wrinkled surfaces whereas moxifloxacin-only powders were spherical and smooth and ethionamide-only powders were angular-shaped flakes. The combination powders had low water content (<2.0%). All the powders were physically stable at 15% RH and 25 ± 2 °C during 1-month storage and tolerated by bronchial epithelial cell-lines up to 100 µg/ml. The improved aerosolization of the combination formulation may be helpful for the effective treatment of drug-resistant tuberculosis. Further studies are required to understand the mechanisms for improved aerosolization and test the synergistic activity of the combination powder. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/31014129/Carrier_free_combination_dry_powder_inhaler_formulation_of_ethionamide_and_moxifloxacin_for_treating_drug_resistant_tuberculosis_ L2 - https://www.tandfonline.com/doi/full/10.1080/03639045.2019.1609494 DB - PRIME DP - Unbound Medicine ER -