| Voriconazole is a derivate of fluconazole, which acquires an improving potency andspectrum against fungal. However, its poor solubility and stability limits its clinical use.Voriconazole injections on the market contain beta cyclodextrin (β-CD) derivatives whichincrease the aqueous solubility of Voriconaozle but limit the application of the drug for itsnephrotoxicity and haemolysis. It is necessary to introduce a new pharmaceutics techniqueto reduce the side effects and increase the therapeutic effect.In this paper, voriconazole was solubilized in Solutol HS15and its freeze-driedpowder was prepared, the preparation and technological conditions were studied andoptimized. The main results are as follows:（1） HPLC method was established for the detection of voriconazole. The sensitivity,precision, stability and recovery of the method all met the requirements of thestudy methodology. Voriconazole had a good linear relationship in the scope of10.03-200.64μg/mL. The solubility of voriconazole in different pH was measured.And the effects of temperature, acid and alkali on voriconazole were studied. Thelong stability of voriconazole injections was investigated at last.（2） Voriconazole injections were prepared. It was found that there should be at least1.4g Solutol HS15to solubilize50mg voriconazole. Stirring rate and time,injecting rate had little influence on the preparation process. EDTA, glycerol and1,2-propylene glycol couldn’t improve the stability of voriconazole. Andpoloxamer188, Tween80and PEG400had no help in improving the solubility ofvoriconazole.（3） Voriconazole freeze-dried powder was prepared.5%glucose was selected as thebest cryoprotectant. Samples were dried for36h to get good freeze-dried products.Proper volume before freeze-dried was also important for good products. Thefreeze-dried process had no effect on the drug and improved the stability ofvoriconazole. And that’s good for its storage. |
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