Ways to increase the solubility of voriconazole

05 Jul.,2021

Hydroxypropyl betadex and betadex sulfobutyl ether sodium can be uese to increase solubility of voriconazole


1. Use cyclodextrin and its derivatives as solubilizers;

2. Using the mixture of organic solvent propylene glycol and ethanol as a special solvent, voriconazole is initially dissolved and then diluted into other liquids.

Why don't all voriconazoles add cyclodextrin derivatives as solubilizers to increase their solubility?

Cyclodextrin derivatives have strong water solubility and high thermal stability. They have the characteristics of "outer hydrophilic, inner hydrophobic". They are prone to poorly soluble drugs and form clathrates. They are a safe and effective drug solubilizer, stabilizer and absorption accelerators are new excipients for pharmaceutical preparations that have been widely used in recent years. Compared with voriconazole equipped with a special solvent, the dissolution time and operation steps can be shortened.

However, compared with ethanol and propylene glycol, the cost of cyclodextrin itself is higher, and the original manufacturer has patents for pharmaceutical preparations. From these two perspectives, domestic manufacturers use ethanol and propylene glycol as solvents, but ethanol itself is highly irritating, has anesthetic effects on nerves, and has a strong damaging effect on the liver.

The difference between the two cyclodextrin derivatives:

In order to improve the physicochemical and biological properties, the structure of cyclodextrin has been modified. At present, the commonly used derivatives of cyclodextrin are hydroxypropyl-β-cyclodextrin and sodium sulfobutyl-β-cyclodextrin.

Betadex sulfobutyl ether sodium is used as the inclusion material in the prescription of imported voriconazole powder for injection (Weifan). However, due to the excipient betadex sulfobutyl ether sodium, there is no approved injection-grade product in China (currently there are several consistent evaluations of injectable voriconazole in the review process). The domestically-made voriconazole for injection currently on the market uses hydroxypropyl-β cyclodextrin as an excipient.

Betadex sulfobutyl ether sodium contains a more polar sulfonic acid group in its molecule, so the kidney has little reabsorption effect on it, faster excretion, and has the advantages of low nephrotoxicity, good water solubility, and low hemolysis. Compared with unmodified β-cyclodextrin, its nephrotoxicity is greatly reduced, and the hemolysis of Betadex sulfobutyl ether sodium is far less than β-cyclodextrin and hydroxypropyl-β-cyclodextrin.