Degradation kinetics of hydrolytically susceptible drugs in O/W emulsions--effects of interfacial area and lecithin.
To investigate the influence of the interfacial area and the emulsifier lecithin on the degradation rate of drugs prone to hydrolysis in parenteral lipid O/W emulsions we measured the degradation kinetics of phenyl salicylate in systems consisting of Miglyol as oil, buffered and isotonized aqueous phase and lecithin as emulsifier. Two-layer oil over water systems and emulsions of different oil droplet diameters and emulsifier contents were tested and a kinetic model was developed to interpret the results. The measurements showed a complex influence of interfacial area and liposomal concentration on the hydrolysis of phenyl salicylate. The interface between oil and water does not act as a diffusion barrier for phenyl salicylate, neither without nor with an interfacial layer of emulsifier. However, the presence of the layer and the formation of liposomes by the emulsifier lead to an overall acceleration of the hydrolysis. Three effects, partially counteracting each other, could be distinguished: the increase of phenyl salicylate concentration in the aqueous phase with increasing emulsifier concentration, the acceleration of hydrolysis with increasing interfacial area and the protection from hydrolysis by incorporation of phenyl salicylate into the emulsifier liposomes.
Krickau
D P
DP
Research and Development, Schering AG, Muellerstr. 178, D-13342 Berlin, Germany.
Mueller
R H
RH
Thomsen
J
J
D000465:Algorithms; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry; D009821:Oils; D009997:Osmotic Pressure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D017785:Photons; D012459:Salicylates / Q000737:chemistry; D012995:Solubility; D013057:Spectrum Analysis; D013500:Surface Tension; D014867:Water
D002021:Buffers; D004655:Emulsions; D008081:Liposomes; D009821:Oils; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D012459:Salicylates; D014867:Water; C026041:phenyl salicylate