ABSTRACT
In this article, a nanosuspension of AmB was prepared and mixed with the preformed parenteral emulsion Lipofundin and subjected to high-pressure homogenization (SolEmuls technology). Characterization was performed by photon correlation spectroscopy (PCS), laser diffractometry (LD), and zeta potential measurements. Drug incorporation was studied by using light microscopy. The produced emulsions were further investigated by comparing them with the commercially available Fungizone in regard to antifungal efficiency and toxicity. Results suggest that through the SolEmuls process the AmB forms a reservoir, out of which it is released in such a manner that it is more efficient and less toxic than Fungizone.
Subject(s)
Amphotericin B/chemistry , Amphotericin B/pharmacology , Amphotericin B/administration & dosage , Candida tropicalis/drug effects , Drug Combinations , Drug Stability , Emulsions , Erythrocytes/drug effects , Erythrocytes/metabolism , Hemoglobins/metabolism , Lecithins/chemistry , Microbial Sensitivity Tests , Nanotechnology/methods , Particle Size , Phospholipids/chemistry , Potassium/metabolism , Solubility , Sorbitol/chemistry , Spectrophotometry , Static Electricity , Surface Properties , Suspensions/chemistryABSTRACT
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.
