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A triple combination 'nano' dry powder inhaler for tuberculosis: in vitro and in vivo pulmonary characterization

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Abstract

Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients. 

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Acknowledgements

The authors would like to thank Lupin Ltd. (Aurangabad, India) for the gift samples of Isoniazid, Pyrazinamide, and Rifampicin; Capsugel (Mumbai, India) for the gift sample of inhalation grade size 3 capsules; and DFE Pharma (Goch, Germany) for the gift sample of inhalation grade lactose.

Funding

This study was funded by University Grants Commission-Basic Science Research (UGC BSR).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga-400 019, Mumbai, Maharashtra, India

    Manasi M. Chogale, Sagar B. Dhoble & Vandana B. Patravale

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  1. Manasi M. Chogale
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  2. Sagar B. Dhoble
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  3. Vandana B. Patravale
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Contributions

Conceptualization: Manasi Chogale, Sagar Dhoble, Vandana Patravale; methodology: Manasi Chogale, Sagar Dhoble, Vandana Patravale; formal analysis and investigation: Manasi Chogale, Sagar Dhoble, Vandana Patravale; writing: Manasi Chogale; original draft preparation: Manasi Chogale; writing: review and editing: Manasi Chogale, Vandana Patravale; supervision: Vandana Patravale.

Corresponding author

Correspondence to Vandana B. Patravale.

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Ethics approval

The in vivo lung deposition study was performed as per the procedures and guidelines of the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA), India, at the Institute of Chemical Technology, Mumbai, India. The experiments were performed on receiving approval of the animal study protocol submitted to the Institutional Animal Ethics Committee (IAEC) of the Institute of Chemical Technology (Protocol no. IAEC/ICT/2017/P56: To study the biodistribution of developed novel nanoformulation for tuberculosis via pulmonary route).

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The authors declare no competing interests.

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Chogale, M.M., Dhoble, S.B. & Patravale, V.B. A triple combination 'nano' dry powder inhaler for tuberculosis: in vitro and in vivo pulmonary characterization. Drug Deliv. and Transl. Res. 11, 1520–1531 (2021). https://doi.org/10.1007/s13346-021-01005-5

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