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Incorporation of alphaxalone into different types of liposomes.

The poor solubility of steroid anaesthetics in water has been a serious drawback in the development of clinically acceptable intravenous formulations. The use of Cremophor EL to solubilize steroids such as alphaxalone led to unacceptable hypersensitivity reactions and consequent withdrawal of this anaesthetic. In principle, liposomes can act as a safe solvent for the intravenous administration of alphaxalone. We report the incorporation of [14C]acetylated alphaxalone in both multilamellar vesicles and stable plurilamellar vesicles prepared from a range of amphiphiles including synthetic polyhydroxyl lipids. For both types of preparations, addition of cholesterol to phosphatidylcholine-based lipids caused an increase in encapsulation efficiency. Maximum encapsulation was achieved with the stable plurilamellar vesicle preparation of 1-stearyl-2-myristylglycerate-3, N-methylglucamine:cholesterol:egg phosphatidylcholine (78%). The rate of efflux of this anaesthetic from a range of liposomes was measured in serum. The highest rate (85% after 30 min) was observed with an equimolar egg phosphatidylcholine:cholesterol stable plurilamellar vesicle preparation. From these studies it can be concluded that liposomes offer a suitable alternative for intravenous delivery of steroidal anaesthetics.[1]

References

  1. Incorporation of alphaxalone into different types of liposomes. Dean, T.P., Hider, R.C. J. Pharm. Pharmacol. (1993) [Pubmed]
 
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