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Background. In N.N. Blokhin Russian Cancer Research Center have been synthesized a number of hypothalamic hormone somatostatin analogues, including pentapeptide cyphetrylin, and drug Cyphetrylin tablets 6 mg has been created. One of the drug standardization step is development of assay technique for acting substance in the final preparation. Objective. Development and validation of cyphetrylin assay in tablets. Materials and methods. The study used cyphetrylin, tablets 6 mg, сyphetrylin powder substance (FSBI “N.N. Blokhin Russian Cancer Research Center”, branch “Naukaprofi”), lactose monohydrate, cellulose microcrystalline, potato starch, povidone, talc, magnesium stearate (European Pharmacopoeia current edition), 95 % ethyl alcohol. Method of assay - spectrophotometry. Results. The technique for assay of сyphetrylin in drug “Cyphetrylin, tablets 6 mg” has been developed. Validation was performed to confirm test validity and accuracy. The technique was estimated by validation characteristics: specificity, linearity, accuracy, precision (repeatability and intermediate precision). Conclusion. The developed technique has the required characteristics: specificity, accuracy, repeatability, intermediate precision, linearity and can be used in the range of 70-130 % of nominal сyphetrylin content in preparation.

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Background. A glycoside derivative of indolocarbazole LHS-1269, one of the new drugs selectively affecting tumors, which was first synthesized at the N.N. Blokhin National Medical-Research Center of Oncology of the Ministry of Health of Russia, is of particular scientific interest. Experimental studies demonstrated a multi-target mechanism of action of this compound. LHS-1269 interacts with several intracellular targets and induces various pathways of cell death. Several innovative models of the dosage forms were designed to achieve the highest antitumor activity of the compound and to perform further preclinical studies.Aim. To develop the methods for the quantitative determination of LHS-1269 in pharmaceutical compositions proposed as a result of the search for the optimal dosage form.Materials and methods. The study analyzed the spectrophotometric characteristics of LHS-1269 solutions in dimethylformamide, dimethylsulfoxide (DMSO) and in the mixture of solvents DMSO–ethyl alcohol, as well as electronic absorption spectra of the excipients in the mixture of solvents DMSO–ethyl alcohol. Spectrophotometric measurements were performed on a Cary 100 spectrophotometer (Varian, Inc., Australia) in the wavelength range from 200 to 500 nm. The standard sample is the substance LHS-1269 (N.N.  Blokhin Oncology Research Center of the Ministry of Health of Russia).Results. The carried out studies showed that LHS-1269 solutions in dimethylformamide, DMSO and mixture of DMSO– ethyl alcohol are suitable for spectrophotometric measurements. Several variants of the methodology for the assay of LHS-1269 in various dosage form models that differ in the content of the active substance and the excipients composition have been developed: LHS-1269 concentrate for solution for injection and infusion; lyophilisate for solution for injection; liposomal lyophilisate for dispersion for injection.Conclusion. Techniques for the assay of LHS-1269 in dosage form models have been developed. It has been shown that the developed techniques are applicable for LHS-1269 quantitative determination in innovative dosage forms containing polymeric low molecular weightsolubilizers, lipids, cholesterol, mono- or oligosaccharides as excipients.

Liposomes are lipid vesicles with an aqueous interior size between 50 nm and 200 nm in diameter. Liposomal drugs currently in clinical use are characterized primarily by their decreased side effects rather than improved therapeutic potency. Significant improvements in the efficacy of liposomal drug therapy may be obtained using thermosensitive liposomes (TSL) in combination with local hyperthermia (HT). TSL release their content at a specific formulation-dependent gel to liquid-crystalline phase transition temperature. At this temperature the membrane's permeability increases by several orders of magnitude. The purpose of present work was preparation of TSL loaded with doxorubicin (Dox) and investigation of their effect on B-16 mouse melanoma and Ehrlich (line ELD) carcinoma in combination with HT. TSL were prepared using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, PEGylated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cholesterol and α-tocopherol acetate in molar ratios of 9:1:0.02:0.2:0.2 (composition 1); 9:1:0.1:0.5 (composition 2); 9:1:0.2:0.75 (composition 3); 9:1:0.3:1 (composition 4); 9:1:0.4:1.2 (composition 5). The extrusion was performed through 200 nm polycarbonate membranes at 50 °C. Dox was loaded into TSL by ammonium ion gradient. Drug-to-lipid ratio was 0.13:1 (w/w). Dox-TSL were lyophilized for better stabilization with 4 % sucrose added as a cryoprotectant. Vesicle size was measured using Nicomp-380 Submicron Particle Sizer. Dox-TSL were separated from untrapped Dox by gel filtration. In biological experiments tumors were transplanted in the shank muscle of mice. Dox-TSL or free Dox were injected in retroorbital sinus of animals at doses of 9 and 4.5 mg Dox per kg body weight. HT treatment of shank with transplanted tumor was performed at 43 °C for 30 min using water bath. Efficacy of Dox encapsulation in TSL of compositions 4 and 5 was 60 % (diameter of vesicles was 175 ± 10 nm). TSL of compositions 2 and 3 encapsulated 88 % and 86 % of Dox, respectively (diameter of vesicles was 160 ± 10 nm). TSL of composition 1 trapped 88-94 % of Dox (diameter of vesicles was 175 ± 15 nm). The composition 1 has been chosen for preparation of lyophilized drug, which has been assessed in biological experiments. The doubling time of B-16 melanoma was 9 days after heating on a background of Dox injection at dose of 9 mg/kg, while heating of tumors after injection of Dox-TSL at doses of 4.5 and 9 mg/kg increased tumor doubling time up to 12 and 16 days, respectively. The doubling time of Ehrlich carcinoma increased from 3 days in the control group up to 14 days for the group of mice administered 9 mg/kg of Dox-TSL followed by HT in 15-20 min. Encapsulation of Dox in TSL has resulted in decrease of its toxicity as judged by animal survival. Thus, Dox-TSL in combination with HT has shown more efficiency than free Dox in suppression of tumor growth.