Posaconazole freeze-dried powder injection and preparation method thereof

Abstract

The invention discloses a posaconazole freeze-dried powder injection and a preparation method thereof. The powder injection comprises an active therapeutic ingredient of posaconazole, a solubilizer of cyclodextrin and a pH conditioning agent. An acid is added in preparation processes to form a salt for solubilization. A mixed solvent comprising an organic solvent and injection water is employed, wherein the concentration of posaconazole in the mixed solvent is 2.5 to 15g / ml, the organic solvent is 3.0 to 10.0% by volume, and the balance is the injection water. In the preparation processes, the posaconazole and the acid are stirred or mixed, the organic solvent is added, the mixture is heated stirred or ultrasonically treated to be uniform, the cyclodextrin solution is added, mixture is stirred to be a clear solution, the pH value of the mixture is adjusted, the injection water is added to a constant volume, pyrogens are removed, and then aseptic filtration, subpackaging and freeze-drying are performed. The posaconazole freeze-dried powder injection of the invention has advantages that: the content of the active therapeutic ingredient is high, the stability is excellent, the powder injection is convenient for transport and storage, and the application of the posaconazole in the field of preparations is expanded.

Description

technical field [0001] The invention relates to an antifungal freeze-dried powder injection of posaconazole and a preparation method thereof, belonging to the field of pharmaceutical preparations. Background technique [0002] Posaconzole is a new type of triazole oral broad-spectrum antifungal drug developed by Schering-Plough, and its chemical name is 4-[4-[4-[4-[[(3R,5R)-5-(2 ,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl] Phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one, the chemical structure is shown below, [0003] [0004] In September 2006, it was approved for marketing by the US FDA. The marketed dosage form is oral suspension, the trade name is Noxafil, and the concentration is 40 mg / L. The compound has good antibacterial activity against Candida species, especially in refractory or invasive fungal infections resistant to polyenes and other triazoles (such as Aspergillus, Fusarium and Zygomycetes, Coccidio...

AI Technical Summary

Problems solved by technology

[0005] The patent document CN1499930A discloses an oral suspension. By adding a thickener and a nonionic surfactant, the bioavailability of posaconazole is improved, but the liquid preparation can only be administered orally. Use is limited in critically ill patients who have difficulty swallowing

In addition, the use of oral suspensions is extremely limited in patients with invasive infections who need to reach the lowest steady-state drug trough concentration as soon as possible

Patent document CN1988887A discloses a posaconazole suspension that is stabilized by phospholipids and can be used for intravenous injection, but the concentration of posaconazole in the suspension is low, and the suspension itself is less stable than other dosage forms , transportation and storage inconvenience

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