SELECTION OF THE COMPOSITION OF A LIPOSOMAL DOSAGE FORM OF A RUSSIAN SOMATOSTATIN ANALOGUE WITH ANTITUMOR ACTIVITY
Objective: To create the composition selection for the liposomal pharmaceutical form for injections derived from soybean phosphatidylcholine (SPC), which is analogue hypothalamic hormone somatostatin (cyphetrylin).
Objective was to create the composition of the liposomal pharmaceutical form for injections of somatostatin analogue cyphetrylin using soybean phosphatidylcholine (SPC).
Methods: The cyphetrylin, active pharmaceutical ingredient (API), developed in the Chemical Synthesis Laboratory, the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation; soybean phosphatidylcholine and polyethylene glycol-2000-distearoylphosphatidylethanolamine (PEG-DSPE, Lipoid, Germany); cholesterol ≥99% (Sigma-Aldrich, Japan). The lipid film hydration method with subsequent liposomal dispersion filtration/extrusion through nylon membrane filters was used for the phospholipid vesicle production. The derived model samples of liposomal dispersion were estimated in terms of quality and efficiency of cyphetrylin encapsulation into vesicles, their average size and the surface charge (ζ-potential), index of polydispersity (PDI) and dispersion viscosity. We used spectral photometry, dispersion laser spectroscopy, electrophoretic particle mobility assay, and viscometry to assess these features.
Results. Based on API and lipid components in different molar ratios, we studied over 15 model liposomal compositions and assessed each lipid's impact in use on quality attributes of resulting dispersions. The pharmaceutical form components' desirable molar ratios determined: cyphetrylin/SPC at 1:60 and SPC/cholesterol/PEG-DSPE at 1:0.2:0.004, were determined. This composition allows cyphetrylin liposomal dispersion production with relatively stable vesicles of uniform size, 176 um in diameter, and a 100% maximum rate of API encapsulation into bilayer.
Conclusion. The technological and chemical/pharmaceutical studies resulted in selecting a preferable composition of an injectable liposomal pharmaceutical form model of somatostatin analogue based on the SPC.
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