Development of inhaled formulation of modified clofazimine as an alternative to treatment of tuberculosis: Clofazimine inhaled formulation for tuberculosis
Citation:
de Castro R.R., Todaro V., da Silva L.C.R.P., Simon A., do Carmo F.A., de Sousa V.P., Rodrigues C.R., Sarmento B., Healy A.M., Cabral L.M., Development of inhaled formulation of modified clofazimine as an alternative to treatment of tuberculosis: Clofazimine inhaled formulation for tuberculosis, Journal of Drug Delivery Science and Technology, 2020, 58Download Item:
Abstract:
Inhalation drug delivery provides a possible useful alternative to oral drug delivery in the treatment of tuberculosis (TB). This work evaluated inclusion complexes of clofazimine (CFZ), an anti-TB drug with low aqueous solubility and potential gastric degradation, in β-cyclodextrin (βCD), γ-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin and sulfobutyl-ether-β-cyclodextrin. A phase solubility study indicated that βCD showed the best inclusion capacity for CFZ, so a CFZ:βCD complex (1:7) was selected for further studies. Particle engineering was performed using spray drying to obtain powders with suitable characteristics for pulmonary delivery and l-leucine was added to enhance powder dispersibility. Thermal and spectroscopic analyses indicated the CFZ:βCD integrity after spray drying, and the presence of l-leucine resulted in less hygroscopic and rougher particles, and a less agglomerated powder. All formulations, and especially those containing l-leucine, showed suitable in vitro deposition performance in the Next Generation Impactor and presented higher aqueous solubility compared to the free drug. In vitro studies showed low toxicity against Calu-3 and CFZ retention in the cell monolayer and apical compartment. These results suggest that the inhalation formulation composed of CFZ:βCD plus l-leucine should improve CFZ pulmonary bioavailability and provide an alternative treatment for TB, acting on the main infection site of the disease.
Author's Homepage:
http://people.tcd.ie/healyamDescription:
PUBLISHED
Author: Healy, Anne-Marie
Type of material:
Journal ArticleSeries/Report no:
Journal of Drug Delivery Science and Technology;58;
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Full text availableKeywords:
Pulmonary delivery, Tuberculosis, Clofazimine, Cyclodextrin, L-leucineDOI:
http://dx.doi.org/10.1016/j.jddst.2020.101805ISSN:
17732247Metadata
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