SolEmuls-novel technology for the formulation of i.v. emulsions with poorly soluble drugs.
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.
Müller
R H
RH
Department of Pharmaceutical Technology, Biotechnology and Quality Management, Free University Berlin, Kelchstrasse 31, 12169 Berlin, Germany. mpharma@zedat.fu-berlin.de
Schmidt
S
S
Buttle
I
I
Akkar
A
A
Schmitt
J
J
Brömer
S
S
D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004338:Drug Combinations; D004356:Drug Storage; D004655:Emulsions; D010316:Particle Size; D010743:Phospholipids; D012995:Solubility; D013012:Sorbitol; D013678:Technology, Pharmaceutical / Q000379:methods*
D000935:Antifungal Agents; D004338:Drug Combinations; D004655:Emulsions; D010743:Phospholipids; C008288:Lipofundin; D013012:Sorbitol; D000666:Amphotericin B