ABSTRACT
Intravenously injectable o/w emulsions of drugs being poorly soluble in water and simultaneously in oils need to be produced by locating the drug in the interfacial lecithin layer, e.g. amphotericin B. For achieving this, up to now organic solvents were required. The objective was to develop a solvent-free production method for such emulsions. Drug and the pre-formed parenteral emulsion Lipofundin were mixed and subjected to high pressure homogenisation. Drug powder and emulsions were characterised regarding size and physical stability by photon correlation spectroscopy (PCS), laser diffractometry (LD) and zeta potential measurements. Drug incorporation was studied using light microscopy, electron microscopy (EM) and a centrifugation test to separate non-dissolved drug. Amphotericin B and carbamazepine were used as model drugs. The high streaming velocities lead to accelerated drug dissolution and partitioning into the interfacial layer (so-called "solubilisation by emulsification", SolEmuls Technology). The interfacial layer could incorporate (solubilise) a certain amount of drug, revealed by EM pictures. Exceeding this concentration, hybrid dispersions were formed consisting of drug-loaded oil droplets and drug nanocrystals of similar size (approximately 200 nm). Both dispersion types are i.v. injectable opening the opportunity to deliver the drug in a concentrated form at desired low injection volume, e.g. 10 mg/ml.
Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Chemistry, Pharmaceutical/methods , Drug Combinations , Emulsions , Phospholipids , Sorbitol , Technology, Pharmaceutical/methods , Drug Storage , Particle Size , SolubilityABSTRACT
Oil in water (O/W) emulsions for parenteral nutrition can be employed as intravenous (i.v.) carriers for drugs that are poorly soluble in water and in oil by localising the drug in the interfacial lecithin layer, e.g. Amphotericin B emulsions. By now, the emulsion production required organic solvents. SolEmuls technology localises the drug in the interfacial layer by a solvent-free high-pressure homogenisation process. SolEmuls was applied to produce Carbamazepine emulsions at increasing drug concentrations from 0.5 to 10mg/ml. Drug powder and Lipofundin emulsion were mixed and homogenised at 1500bar. Characterisation of emulsions and short-term stability were performed by photon correlation spectroscopy (PCS) and laser diffractometry. Drug incorporation (absence of non-dissolved drug crystals) was investigated by light microscopy and a centrifugation test. The emulsions were physically stable and complete drug dissolution is possible up to 3mg/ml. Up to 10mg/ml drug hybrid dispersions of emulsion droplets and ultrafine nanocrystals were obtained. Both, emulsions and hybrid dispersions are suitable as i.v. injectables regarding size and stability.
