THE ANALYSIS OF THE COMPOSITION AND STANDARDIZATION OF THE ORAL DOSAGE FORM OF PLASTOMITIN

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Issue: 
2
Year: 
2017

O.I. Tereshkina Ph.D. (Pharm.), Scientific Secretary, Research Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University E-mail: o.i.ter@yandex.ru E.A. Petryukina Ph.D. (Pharm.), Leading Research Scientist, Laboratory Standardization and Pharmaceutical Technology, Research Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University E-mail: epertr07@yandex.ru O.N. Fedorkin Ph.D. (Biol.), Leading Research Scientist, A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Deputy Director for Registration of «Mitoteh», LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow) E-mail: ofedorkin@mitotech.ru D.E. Esipov Ph.D. (Chem.), Production Director, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow); Associate Professor, Department of Bioorganic Chemistry, Faculty of Biology, Lomonosov Moscow State University E-mail: prod@mitotech.ru T.V. Zinevich Ph.D. (Chem.), Head of Laboratory, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow); Senior Research Scientist, Department of Bioorganic Chemistry, Faculty of Biology, Lomonosov Moscow State University E-mail: zinevich.tatiana@gmail.com T.A. Gorbacheva Head of Production Department, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow) E-mail: gorbachevata@gmail.com T.S. Nevredimova Chief Technologist, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow) E-mail: nevredimovats@mitotech.ru R.S. Zverev Head of Quality Assurance, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow) E-mail: zverev@mitotech.ru V.N. Tashlitskii Ph.D. (Chem.), Head of Quality Control Department, LLC «Mitoinzhenerii Research Institute of Moscow State University» (Moscow) E-mail: tashlitsky@genebee.msu.ru G.V. Ramenskaya Dr.Sc. (Pharm.), Professor, Head of the Department of Pharmaceutical and Toxicological Chemistrynamed after A.P. Arzamastsev, I.M. Sechenov First Moscow State Medical University E-mail: ramenskaia@mail.ru A.Yu. Savchenko Ph.D. (Med.), Leading Research Scientist, Pharmaco Simulation Laboratory, FGBUN NTSBMT FMBA of Russia (Moscow) E-mail: alursav@mail.ru

The article presents the analytical and experimental results of as well as corresponding regulatory documents for new pharma-ceutical Plastomitin, which is an oral pharmaceutical composition containing mitochondrially targeted antioxidant plastoqui-nonyldecyltriphenylphosphonium bromide (PDTP or SkQ1). Here we describe some aspects of the Plastomitin pharmacological activity, the composition including the selection of excipients, the list of quality control (QC) methods, and tests, and values of key validation parameters. One form of PDTP (Visomitin eye drops) is already approved and marketed in Russia. The positive pre-clinical and clinical results were reported for Visomitin treatment of a number of eye diseases such as retinal degeneration, cataract, glaucoma, dry eye syndrome. There is also a large amount of the positive experimental data on the efficiency of systemic PDTP in animal models of vari-ous pathologies (brain injury, ischemia of kidneys and heart, cardiac arhythmia). Taken together these data make the development of PDTP oral formulation quite promising. The developed formulation is intended for application as neuroprotective antioxidant prepara-tion as a concomitant therapy for brain injuries. Our study was based on physicochemical properties PDTP, some published data, and preliminary results of stability studies of PDTP in different compositions. The study included the selection of QC parameters, their valu-ation in the accordance with modern requirements for solutions for oral administration, and development of QC methods. The selection of methods of analysis was based on the results of experimental studies of test formulations, as well as studies of physicochemical properties of their components, i.e. the active pharmaceutical substances and excipients. The authenticity PDTP was proved by two methods: UV spectrophotometry and ultra-high performance liquid chromatography with MS detection. Found QC parameters meet the requirements of section 1.4.1.11 “Solutions” of State Pharmacopeia of Russian Federation XIII-ed. The standard values and ranges for the formulation were set on the basis of analysis of 5 series test samples of the formulations. Our studies resulted in the development of the optimal composition of the formulation and preparation of a draft of normative documentation new pharmaceutical formulation: "Plastomitin, oral solution." This draft documentation includes the following sections: description, identification, pH, density, relative viscosity, impurities (related compounds), extractable volume, microbiological purity, assay, packaging, labeling, storage, shelf life.

Keywords: 
plastomitin
the composition of the dosage form for oral administration
standardization
UV spectrophotometry
ul-tra-high performance liquid chromatography with MS-detection.

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