Physicochemical characterisation of liposomes with encapsulated local anaesthetics

Local anaesthetics may be added to intravenous o/w emulsions of propofol to reduce the initial pain of injection. Due to incompatibility problems of the emulsion on the addition of a local anaesthetic solution, prior encapsulation of the drug within liposomes is suggested. The liposomes were prepared with the sonication method and loaded with either lidocaine hydrochloride (LiHCl) or prilocaine hydrochloride (PrHCl). The liposomal systems were characterised with photon correlation spectroscopy (PCS) in terms of mean particle size and polydispersity. Lamellarity and lamellar thickness were determined by small angle X-ray scattering (SAXS). Visualisation of drug-loaded liposomes was performed with transmission electron microscopy (TEM) after freeze fracture replication of the samples. Depending on the manufacturing procedure mean particle sizes of the drug-free liposomes varied from 150 +/- 9 nm to 102 +/- 2 nm. Drug-loaded liposomes manufactured the same way showed reduced particle sizes of 125 +/- 1 nm and 85 +/- 7 nm, respectively. Determination of bilayer thickness by SAXS yielded 6.2 +/- 0.2 nm in the case of full hydration whereas the bilayer thickness without the hydration shell was just 4.4 +/- 0.2 nm. The small particle sizes achieved are appropriate for intravenous administration. (C) 2004 Elsevier B.V. All rights reserved.