A new formulation concept for drugs with poor water solubility for parenteral application.
The parenteral application of active substances with poor solubility in water is often bound to the use of stabilizing excipients or surfactants with serious undesired side effects. A new concept is introduced based on a drug concentrate, comprising the active substance dissolved in parenterally acceptable organic solvents, and an aqueous dilution medium, which are mixed in a special mixing device immediately prior to application and thus generating the applicable formulation directly prior to administration. Due to the requirement of formulation stability for only a few minutes, the amount of stabilizing agents can be reduced significantly. It can be shown that model drugs dissolved in a mixture of polyoxyethylen glycol, ethanol and soya lecithin as stabilizer may be mixed to an aqueous glucose solution resulting in a parenterally acceptable and administerable dispersion which is physically stable for several minutes. First in vivo data show good tolerability and blood plasma levels which are comparable to conventional solutions.
Jürgens
K
K
Department for Pharmaceutics and Biopharmaceutics, Christian-Albrecht-University Kiel, Germany.
Müller
B W
BW
D000818:Animals; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D000431:Ethanol; D007267:Injections; D009391:Nephelometry and Turbidimetry; D019999:Pharmaceutical Solutions; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents; D014867:Water / Q000737:chemistry
D019999:Pharmaceutical Solutions; D010713:Phosphatidylcholines; D012997:Solvents; D014867:Water; D000431:Ethanol; D011092:Polyethylene Glycols