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Pharmaceutics
Volume 13
Issue 12
10.3390/pharmaceutics13122044
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Article

Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

by
Zitong Shao
1,
Waiting Tai
2,
Yingshan Qiu
1,
Rico C. H. Man
1,
Qiuying Liao
1,
Michael Y. T. Chow
2,
Philip C. L. Kwok
2 and
Jenny K. W. Lam
1,3,*
1
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
2
Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
3
Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, New Territories, Hong Kong, China
*
Author to whom correspondence should be addressed.
Pharmaceutics 2021, 13(12), 2044; https://doi.org/10.3390/pharmaceutics13122044
Submission received: 5 October 2021 / Revised: 10 November 2021 / Accepted: 26 November 2021 / Published: 30 November 2021
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections)
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Abstract

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.
Keywords: capreomycin; dry powder aerosol; inhalation; pulmonary delivery; spray drying; tuberculosis capreomycin; dry powder aerosol; inhalation; pulmonary delivery; spray drying; tuberculosis

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MDPI and ACS Style

Shao, Z.; Tai, W.; Qiu, Y.; Man, R.C.H.; Liao, Q.; Chow, M.Y.T.; Kwok, P.C.L.; Lam, J.K.W. Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics 2021, 13, 2044. https://doi.org/10.3390/pharmaceutics13122044

AMA Style

Shao Z, Tai W, Qiu Y, Man RCH, Liao Q, Chow MYT, Kwok PCL, Lam JKW. Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics. 2021; 13(12):2044. https://doi.org/10.3390/pharmaceutics13122044

Chicago/Turabian Style

Shao, Zitong, Waiting Tai, Yingshan Qiu, Rico C. H. Man, Qiuying Liao, Michael Y. T. Chow, Philip C. L. Kwok, and Jenny K. W. Lam. 2021. "Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy" Pharmaceutics 13, no. 12: 2044. https://doi.org/10.3390/pharmaceutics13122044

APA Style

Shao, Z., Tai, W., Qiu, Y., Man, R. C. H., Liao, Q., Chow, M. Y. T., Kwok, P. C. L., & Lam, J. K. W. (2021). Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics, 13(12), 2044. https://doi.org/10.3390/pharmaceutics13122044

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