DEVELOPMENT OF LYOPHILIZED LIPOSOMAL PHARMACEUTICAL DOSAGE FORM CIFELIN

Abstract

His study objective has been to develop optimal composition of Cifelin sterically stabilized liposomal formulation. The substance of Cifelin synthesized in chemical synthesis laboratory FSBNI «N.N. Blokhin RCRC». All used excipients and reagents conform to the standard documentation. Method of obtaining liposomes includes: a method of obtaining Cifelin multilamellar and unilamellar liposomes dispersions. Liposomal dispersion has been lyophilized on freeze-dryer Edwards Minifast DO.2. Liposomes size has been measured by light diffusion dynamic spectrums copy on Nicomp 380 Submicron Particle Sizer. Quantitative measurement has been conducted by spectrometry in ultraviolet area. Crystals of unenclosed into lipid bilayer Cifelin have been separated by filtration through filter with pore diameter of 0,22 μm. Lipids peroxidation has been estimated by concentration of oxidation final product - MDA. MTT-test has been used to estimate Cifelin LF cytotoxic activity in vitro. In this study the optimum molar ratio of components has been found for liposomal membrane composed of phosphatidylcholine, cholesterol and DSPE-PEG-2000. Composition with lipids molar ratio 165 : 8 : 1 and “lipid: Cifelin” ratio 12 : 1 has been chosen as optimal by entrapment efficiency and appearance, encapsulated API value in this composition has been 98±1 %, liposomal size has been 136±12 nm. On cell line SKOV-3 and Jurkat in vitro cytotoxic effect of Cifelin liposomal drug form has been highly increased. As a result of the study drug product “Cifelin lyophilized liposomal for injections 17 mg” has been developed.