Test Dissolution for quality control of water-insoluble somatostatine analog

Background. Test Dissolution, which confirms the release of the active substance, is one of the most important criteria for the quality of tablets. This test significance is determined by potential correlation between the drug absorption in vivo and its release from the dosage form. It is especially difficult to develop the test Dissolution for substances that are poorly soluble in water. Aim. To develop a test Dissolution method for cyphetrylin tablets, 60 mg and to study the release of active substance. Materials and methods. In the work we used an original analogue of somatostatin – cyphetrylin, synthesized in the laboratory of chemical synthesis of N.N. Blokhin National Medical Research Center for Oncology of the Russian Ministry of Health. The test was developed for cyphetrylin tablets, 60 mg. The study was carried out on a dissolution tester Erweka series 700 (type II – Paddle (Erweka, Germany), using hydrochloric acid and isopropyl alcohol and their mixture as a dissolution medium. Quantitative determination of released cyphetrylin was carried out on a Agilent Cary® 100 recording spectrophotometer (Agilent Technologies, USA). Results. Optimal conditions were selected to determine the release of cyphetrylin from tablets, 60 mg. Since cyphetrylin is insoluble in water, it is proposed to use a mixture of hydrochloric acid and isopropyl alcohol in a ratio 3:2 as a dissolution medium. It was shown that a paddle rotation speed of 100 rpm provides the release of cyphetrylin normalized quantity into the dissolution medium in 45 min. A method for cyphetrylin assay in a medium by direct spectrophotometry has been developed. Evaluation of the cyphetrylin release profile showed its gradual release from the tablets, which can be described by a linear relationship in accordance with the Higuchi equation. Conclusion. As a result of the research, a test Dissolution procedure has been developed and the release profile of cyphetrylin from tablets, 60 mg, was assessed. Experimental data showed that in the selected conditions cyphetrylin release from the tablets is more than 80 % and meets the requirements of the Russian State Pharmacopoeia XV ed.