Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2016 Vol: 8 Issue: 3

Formulation of Amphotericin B-lipid derivatives and feasibility for nebulization and their stability study

Abstract

The aim of study was water insoluble amphotericin B (AmB) to be converted into highly water soluble and stable form of solution or micronized suspension form for nebulization. Amphotericin B (AmB) is the drug of choice for most commonly used to treat life-threatening conditions such as cryptococcosis, histoplasmosis, and invasive pulmonary aspergillosis. AmB in lipid drug carriers (SDCS, SC, SDC, KC and KDC) were used to prepare reconstituted dry power formulations by lyophilization process (freeze drying). Among five lipid carriers, KC and KDC were successfully synthesized in a laboratory and characterized by FTIR. AmB-lipid derivatives were reconstituted with distilled water to obtain 5mg/ml of AmB. Their physicochemical parameters (particle size, zeta potential and UV spectroscopy) were monitored. In these formulations all particles were quite stable in size range 17.2 to 73.9 nm during one week after reconstitution. Zeta potential values were found in range between – 29.17 to – 45.53 mV. The nebulizer flow rate was 8 L/min for 2 min and air flow rate in ACI was 28.3 L/ min was operated by vacuum pump suction. The MMADs of all AmB-lipid formulations were obtained between 1.70-2.05 μm with high FPF (70-80%) were characterized by using jet nebulizer (West med) and Andersen Cascade Impactor (stages 0 to 7) (ACI) in vitro study. The results suggest that all AmB-lipid formulations are uniform and stable with in the storage period of six months in the air tight opaque container in a refrigerator condition (2-8ºC). The drug content and assay was carried out by HPLC method. An assay of the AmB showed that the all AmB-lipid formulations contents were closed to 100%. Among different lipid derivatives, sodium deoxycholate sulfate (SDCS) gave the highest particle size and zeta potential value. UV spectra were recorded between 300 to 450 nm, it was confirmed that no markedly visible shifted spectra were observed during first and seven days of reconstituted samples.