Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins.
The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.
Brewster
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ME
Estes
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KS
Bodor
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N
D000777:Anesthetics / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins; D003912:Dextrins; D004355:Drug Stability; D011277:Pregnanediones / Q000008:administration & dosage*; D012996:Solutions; D013213:Starch; D013501:Surface-Active Agents
D000777:Anesthetics; D003505:Cyclodextrins; D003912:Dextrins; D011277:Pregnanediones; D012996:Solutions; D013501:Surface-Active Agents; D013213:Starch; C006477:alphaxalone