Investigation On The Preparation Of Oxaliplatin Phospholipid Complex And Its Application In Intravenous Delivery System

Oxaliplatin (OP) is an organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane and with an oxalate ligand as a leaving group. It is an antineoplastic agent most commonly used to treat cancer of the large bowel. OP is poorly soluble in water and oil. Marketable OP injection is supplied as an aqueous solution at a concentration of 5 mg/ml and is recommended to be administered with doses of 130mg/m~2, so the infusion volume is fairly high. The lipophobic property of OP may keep it from entraping in lipid delivery systems. Moreover OP have many side effects, particularly neurosensory and pulmonary toxicity. All of the above limit the clinical application and dosage forms development of OP. Considering that drug phospholipid complexes (PLC) can improve the solubility of drugs in both water and oil, OPPLC was prepared using soybean phospholipid and applied to the intravenously injectable fat emulsion and nanosuspension in this investigation.The OPPLC was prepared by solvent evaporation method using binding ratio of OP and phospholipid as evaluation parameter. The formulation was optimized by single factor test and orthogonal design, and then the ratio of phospholipid to OP was particularity studied. The formation of OPPLC was greatly influenced by solvent, concentration and reactant ratio. The OPPLC was conformed by differential scanning calorimetry (DSC). The solubility in water and the oil/water apparent partitions in n-octanol of OPPLC were investigated. The results showed that solubility in both water and n-octanol of the prepared OPPLC were significantly improved.The entrapment efficiency of OP in fat emulsion was determined by HPLC after centrifugation. OP is hardly kept in oil phase in its original forms, with the entrapment efficiejcy less than 5%, while in OPPLC forms, the entrapment efficiency increased to 22%, which is still too low to be accepted for fat emulsion.For many decades, Coarse solid suspensions have been produced for intramuscular or subcutaneous injection. In recent years, the pharmaceutical industry has been increasingly interested in the use of nanosuspensions for intravenous injection. Nanosuspensions are submicron colloidal dispersion, consisting essentially of pure drug, require only a minimum amount of surfactants for stabilization. Production technologies currently used are pearl milling...