Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment

[Display omitted] •Moxifloxacin-metformin (MoxMet) association exhibited physical–chemical compatibility.•L-leucine was identified as a critical variable for the spray drying process.•Spray-dried MoxMet formulations suitable for dry powder inhalers (DPI) were produced.•The co-formulation showed redu...

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Bibliographic Details
Published in:	International journal of pharmaceutics Vol. 666; p. 124740
Main Authors:	Simon, A., Velloso-Junior, S.O., Mesquita, R.D., Fontao, A.P.G.A., Costa, T.E.M.M., Honorio, T.S., Guimaraes, T.F., Sousa, E.G.R., Viçosa, A.L., Sampaio, A.L.F., do Carmo, F.A., Healy, A.M., Cabral, L.M., Castro, R.R.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 05-12-2024
Subjects:	Dry powder inhaler Host-directed therapy Metformin Moxifloxacin Pulmonary delivery Tuberculosis Dry powder inhaler Tuberculosis Host-directed therapy Metformin Moxifloxacin Pulmonary delivery
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Summary:	[Display omitted] •Moxifloxacin-metformin (MoxMet) association exhibited physical–chemical compatibility.•L-leucine was identified as a critical variable for the spray drying process.•Spray-dried MoxMet formulations suitable for dry powder inhalers (DPI) were produced.•The co-formulation showed reduced in vitro lung cell toxicity. Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance. Studies have already shown the beneficial role of the oral antidiabetic metformin as an anti-tuberculosis adjuvant drug. This work aimed to develop an inhalatory dry powder co-formulation of metformin and moxifloxacin to figure out a future option for P-TB treatment. Pre-formulation evaluations indicated the physicochemical compatibility of constituents, demonstrating powder crystallinity and acceptable drug content. Eight moxifloxacin-metformin dry powder formulations were produced by spray drying, and solid-state characterizations showed partial amorphization, ascribed to moxifloxacin. Four formulations containing L-leucine exhibited micromeritic and in vitro deposition profiles indicating pulmonary delivery suitability, like spherical and corrugated particle surface, geometric diameters < 5 μm, high emitted doses (>85 %), and mass median aerodynamic diameters between 1–5 μm. The use of a second spray dryer model further optimized the aerodynamic properties and yield of the best formulation, demonstrating the influence of the equipment used on the product obtained. Moreover, the final formulation showed high in vitro cell tolerability and characteristics in permeability studies indicative of good drug retention in the lungs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0378-5173 1873-3476 1873-3476
DOI:	10.1016/j.ijpharm.2024.124740