Mohammad A M Momin1, Shubhra Sinha1, Ian G Tucker1, Colin Doyle2, Shyamal C Das3. 1. New Zealand's National School of Pharmacy, University of Otago, 18 Frederick Street, Dunedin 9054, New Zealand. 2. The University of Auckland, 20 Symonds Street, Auckland, New Zealand. 3. New Zealand's National School of Pharmacy, University of Otago, 18 Frederick Street, Dunedin 9054, New Zealand. Electronic address: shyamal.das@otago.ac.nz.
Abstract
BACKGROUND: Kanamycin, an injectable agent, is currently used to treat drug-resistant tuberculosis (TB). Parenteral kanamycin causes high systemic toxicity which could be avoided by direct delivery to the lungs. This study focused on producing a highly aerosolizable dry-powder of hygroscopic kanamycin by spray-drying with l-leucine. METHODS: Kanamycin powders were prepared with different concentrations (0, 5, 10, 15 and 20% w/w) of l-leucine using the Buchi B-290 Mini Spray-Dryer. In vitro aerosolization efficiency, particle size, morphology, crystallinity, surface composition, drug-excipient interaction and moisture content of the powders were characterized by a Next Generation Impactor (NGI), laser diffraction, scanning electron microscopy, X-ray diffractometry, XPS, ATR-FTIR and thermogravimetric analysis. The physicochemical and aerosolization stability of the powders were investigated after one-month storage at 25±2°C/15% RH and 25±2°C/75% RH. The cytotoxicity on Calu-3 and A549 cells of the kanamycin powders was evaluated by MTT assay. RESULTS: The spray-dried powder particles were in the inhalable size range (<6.1μm). The powders with l-leucine were wrinkled in shape, amorphous in nature and had low moisture content (<5.0%). Kanamycin with 5% (w/w) of l-leucine showed the best aerosolization efficiency of 73.0±2.5%. The powders remained stable during storage at 25±2°C/15% RH and tolerated by respiratory cell lines. CONCLUSION: l-leucine improved the aerosolization of kanamycin by surface modification, which may be helpful for the effective treatment of drug-resistant tuberculosis.
BACKGROUND:Kanamycin, an injectable agent, is currently used to treat drug-resistant tuberculosis (TB). Parenteral kanamycin causes high systemic toxicity which could be avoided by direct delivery to the lungs. This study focused on producing a highly aerosolizable dry-powder of hygroscopic kanamycin by spray-drying with l-leucine. METHODS:Kanamycin powders were prepared with different concentrations (0, 5, 10, 15 and 20% w/w) of l-leucine using the Buchi B-290 Mini Spray-Dryer. In vitro aerosolization efficiency, particle size, morphology, crystallinity, surface composition, drug-excipient interaction and moisture content of the powders were characterized by a Next Generation Impactor (NGI), laser diffraction, scanning electron microscopy, X-ray diffractometry, XPS, ATR-FTIR and thermogravimetric analysis. The physicochemical and aerosolization stability of the powders were investigated after one-month storage at 25±2°C/15% RH and 25±2°C/75% RH. The cytotoxicity on Calu-3 and A549 cells of the kanamycin powders was evaluated by MTT assay. RESULTS: The spray-dried powder particles were in the inhalable size range (<6.1μm). The powders with l-leucine were wrinkled in shape, amorphous in nature and had low moisture content (<5.0%). Kanamycin with 5% (w/w) of l-leucine showed the best aerosolization efficiency of 73.0±2.5%. The powders remained stable during storage at 25±2°C/15% RH and tolerated by respiratory cell lines. CONCLUSION:l-leucine improved the aerosolization of kanamycin by surface modification, which may be helpful for the effective treatment of drug-resistant tuberculosis.
Authors: Tushar Saha; Shubhra Sinha; Rhodri Harfoot; Miguel E Quiñones-Mateu; Shyamal C Das Journal: Pharmaceutics Date: 2022-07-08 Impact factor: 6.525
Authors: Mohammad A M Momin; Bhamini Rangnekar; Shubhra Sinha; Chen-Yi Cheung; Gregory M Cook; Shyamal C Das Journal: Pharmaceutics Date: 2019-10-01 Impact factor: 6.321
Authors: Khaled Almansour; Iman M Alfagih; Alhassan H Aodah; Fawaz Alheibshy; Raisuddin Ali; Turki Al Hagbani; Mustafa M A Elsayed Journal: Pharmaceutics Date: 2021-12-30 Impact factor: 6.321