Formulation and evaluation of a propanidid hydroxypropyl-β-cyclodextrin solution for intravenous anaesthesia

Propanidid is a short acting anaesthetic with poor solubility in water. It was formerly marketed for clinical use as an intravenous (i.v.) anaesthetic in Cremophor EL(R) (Epontol(R), propanidid 50 mg ml(-1)) but this was withdrawn due to anaphylactoid reactions to the vehicle. This paper reports on an aqueous formulation using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as a solubiliser. Phase solubility analysis showed a linear increase in the solubility of propanidid to a maximum of about 80 mg ml(-1) (15 times its solubility in water) in 50% w/v HP-beta-CD. A 50 mg ml(-1) solution in 42% w/v HP-beta-CD was stable to autoclaving and on storage for at least 12 weeks at 42 degrees C. The efficacy of the formulation as an i.v. induction agent was compared with that of a commercial propofol formulation (Diprivan(R), propofol 10 mg ml(-1)) in rats. Induction was rapid and independent of dose whereas sleep duration was dose dependent. Both induction time and sleep duration were significantly shorter for the propanidid formulation. The solution of propanidid in aqueous HP-beta-CD is simple to prepare, stable and effective as a short acting i.v. anaesthetic. Its potential in clinical practice remains to be evaluated. (C) 1997 Elsevier Science B.V.