Kotov А.G., Shishko Т.V., Коtоvа Е.Е., Vovk О.G.
State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines», Kharkiv
Questions the introduction into the SPU of the national monograph «Viburnum bark»
The comparative analysis of quality indices of herbal drug viburnum bark (Viburnum opulus L.) and black haw bark (V. prunifolium L.) ⎯ kinds, which are described in the leading pharmacopoeias, shows the feasibility of the development of modern methods of standardization of raw materials. Seven samples of viburnum bark for compliance with the quality requirements by normative documentation was studied.
For identification of biologically active substances in the viburnum bark a standardized method thin layer chromatography (TLC) using a catechol as a marker is developed. The method for the quantitative determination of biologically active substances in the viburnum bark is developed. The basis for standardized method of the State Pharmacopoeia of Ukraine (SPU) «Determination of tannins in herbal drugs» was used. With the development of quantitative method determination of biologically active substances in the viburnum bark we tested the precision of the results determination of tanins. For other indicators of quality of the viburnum bark the regulation contained in the GF XI taking into account the data obtained in the analysis of 7 samples of raw materials was used.
Based on studies a project of the national monograph SPU «Viburnum bark» was developed.
Keywords: Viburnum bark, black haw bark, identification, quantitative determination, monograph, State Pharmacopoeia of Ukraine.
State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines»
AMITRAZ assay in «Akramit» veterinary drug by HPLC method with monolithic column
In modern analytical normative documents the amitraz assay in veterinary drug «Akramit» carried out using gravimetric method. This method is non-selective and did not allow to obtain reliable results. For the purpose of obtaining authentic results and reclining of the analysis time, HPLC assay method was developed.
As amitraz is practically insoluble in water, its elution was done by mobile phase with high organic modifier concentration using. «Chromolith® SpeedROM RP-18e» monolithic column was used for analysis time and acetonitrile usage reducing. Analysis was done by using 50 mm × 4.4 mm chromatographic column and acetonitrile – phosphate buffer solution pH 2.5 (0.02 М LiH2PO4 + H3PO4) (85:15) mobile phase. Detection valve length was 289 nm and injection volume was 5 μl. Analysis time was 2 min. The proposed method is characterized by linearity in the amitraz concentration in the range of (80-120) % from nominal value with correlation coefficient 0.99936. Statistically significant systematic error is practically absent (0.015 %).
Keywords: amitraz, «Akramit», monolithic column, highperformance liquid chromatography.
Vovk G.V., Koshovyi O.M., Komisarenko A.M.
National University of Pharmacy, Kharkov, Ukraine
Determination of parameters for standardization of the Salvia officinalis leaves dry extract
Standardization parameters of the dry extract from Salvia officinalis leaves obtained by complex processing were proposed.
Study of phenolic compounds of the dry extracts from Salvia officinalis leaves by HPLC revealed 15 phenolic compounds, including 3 hydroxycinnamic acid — coffee, chlorogenic and rosemary; 6 flavonoids — apigenin, luteolin, quercetin 3-metoksilyuteolin, luteolin-7-O-glucoside and quercetin- 3-O-arabynozyd; 6 non-identified substances. The dominant substances are rosemarinic and chlorogenic acid, luteolin-7-Oglucoside. According to published data phenolic compounds provide anti-inflammatory activity. The model of formalin edema indicate a pronounced anti-inflammatory activity of the dry extracts obtained by complex processing. The maximum antiexudative effect of the dry extracts was observed at a dose of 25-30 mg/kg. So the standardization of the extracts, we decided to hold by contents of phenolic compounds. The requirements and methods of State Pharmacopeia of Ukraine were used for extracts standardization. For the dry extract obtained after the production of essential oils such standardization parameters were defined: a description, identification are carrying out by thin layer chromatography to ensure the presence of chlorogenic acid and luteolin-7-Oglucoside, monitor the loss in weight on drying (no more than 5 %), content of heavy metals (no more than 0.01 %), flavonoids (more than 4 %) and the amount of phenolic compounds (more than 20 %). The dry extract from sage leaves obtained after the separation of ethylacetate fraction in addition to the proposed options should be control to the residual amount of ethyl acetate. The analysis of the five series of extracts was carried out. All extracts meet the proposed requirements and after further validation these parameters will be used to develop methods for quality control of the dry extracts from Salvia officinalis leaves obtained by complex processing.
Keywords: phenolic compounds, leaves, Salvia officinalis, dry extract, complex processing, standardization.
Zaporozhye State Medical University, Ukraine
Study by HPLC-DAD-MS retention regularities of the 1,2,4-triazoles-3-tione series intermediate materials in the synthesis of active pharmaceutical ingredients for medicine manufacture
The aim of the study was determination of the retention dependence from acetonitrile content in the mobile phase for HPLC-DAD and HPLC-MS for series of the 1,2,4-triazole-3- thions ⎯ intermediate substances in the synthesis of the salts of 1,2,4-triazole-3-thioacetate acids. These retention regularities will be used for the development of the quantitative methods of determination these substances both individually and an impurities together with the hydrazides and carbothioamides of acids. LC MS: Agilent 1260 Infinity HPLC System (degasser, binary pump, autosampler, single quadrupole mass spectrometer Agilent 6120 with electro-spray ionization (ESI), diode-array detector) software package OpenLAB CDS. Column Zorbax SB-C18, 30 mm × 4.6 mm; 1.8 microns. Most of the studied 1,2,4-triazole-3-thions shown distributive retention mechanism. The correlation between LogD and capacity factor of studied compounds at 15 % acetonitrile content was established, it has exponential character. The correlation between LogD and decimal logarithms capacity factor of studied compounds at 15 % acetonitrile content was established, it has approximately linear character.
Keywords: 1,2,4-triazole-3-thions, column liquid chromatography, retention regularities, diode-array detector, single quadrupole mass spectrometer.
Grigorieva H.S., Kacai O.G., Konakhovich N.Ph., Prokhorov V.V., Stadnichenko O.V., Schvetc V.I., Krasnopolskii Ju.M.
National Technical University «Kharkiv Polytechnic Institute», Ukraine
State Institution «Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine»
NanoMedTech LLC, Ukraine
The real nanopharmacology: 25 years of working up and using of liposomal medications in Ukraine
The article contains the results of investigations having been performed during 25 years by its authors while producing the liposomal pharmaceutical forms. There has been offered a fundamental processing platform for producing the liposomal drugs, as well as considered the main methods of introduction of the active pharmaceutical ingredients into liposomes and those of drugs control and standardization. There has been proved the efficiency of the clinical use of the following drugs: Lipin, Lipodox, Lioliv, Lipoflavon. The liposomal forms of active pharmaceutical ingredients (irinotecan, oxaliplatin, cytochrome C, docetaxel, etc.) have been offered. The prospect of liposomal pharmaceutical forms creation and use is being discussed. The drugs offered are at different stages of pre-clinical and clinical research. The range of the drugs offered has been registered and used in medical practice in Ukraine for 25 years.
Keywords: nanopharmacology, liposomes, liposomal drugs, active pharmaceutical ingredients, methods of introduction of the active pharmaceutical ingredients, technology standardization.
Hudz N.I., Fetko M.M., Korytniuk R.S., Davtian L.L., Georgievsky G.V.
Danylo Halytsky Lviv National Medical University, Ukraine
Shupyk National Medical Academy of postgraduate education, Ukraine
State Enterprise «Ukrainian Scientific Pharmacopoeial Center
for Quality of Medicines»
Requirements for preparation of medicinal products in pharmacies in the countries of the European Union
This article views the main statements of Resolution CM/ResAP (2011)1 on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients, adopted by the Committee of Ministers on 19.01.2011. The resolution was considered by us for the purpose of nearing, adoption, and/or implementation of its statements into the domestic legal, regulatory and technical documents on the requirements of the preparation of medicinal products in pharmacies. According to this Resolution, pharmacy preparation is advisable if a suitable pharmaceutical equivalent with a marketing authorization is either not authorized or not available. Before preparation, a risk assessment should always be carried out in order to define the level of the quality assurance system which should be applied to the preparation of the medicinal product. Risk management skills considered in Resolution AP (97)2, which was adopted on 09.30.1997 by Committee of Ministers, as a subject which should be introduced in the initial and further training of pharmacists. Resolution CM/ResAP (2011)1 provides guidance on the determination of the level of risk of a pharmacy preparation and defines the criteria for the use of the certain type of quality assurance systems: good manufacturing practice or good practices for the preparation of medicinal products in health care establishments. In order to establish the degree of risk for a pharmacy preparation it is offered risk-based decision matrix which takes into consideration 5 such factors: a route of drug administration, the complexity of the technological process, the method of delivery of a pharmacy preparation to the patient, pharmacological properties, and the amount of a pharmacy preparation prepared annually. Also, the resolution provides the statement that pharmacy preparations should always be distributed by a dispensing pharmacy because this pharmacy receives the prescription for the patient. Some statements of the Resolution are recommended to implement to the relevant legislative documents of Ukraine and in the educational process of training of pharmacists in the pre- and post-graduation stage.
Keywords: pharmacy preparation, the degree of risk, good practices for the preparation of medicinal products in health care establishments.
Bezuglaya О.P., Melnikova О.N., Gemerova К.G., Lyapunov О.М., Zinchenko І.О.
State Scientific Institution «Institute for Single Crystals» of National Academy of Sciences of Ukraine, Kharkov, Ukraine
«Scientific Centre of Developments and Innovations» Ltd., Kharkov, Ukraine
Efficacy of antimicrobial preservation of certain hydrophilic non-aqueous solvents in aqueous solutions and gels
The efficacy of antimicrobial preservation of aqueous solutions of certain hydrophilic non-aqueous solvents such as Nmethylpyrrolidone (N-MP), propylene glycol (PG), ethanol as well as aqueous solutions of mixed solvents N-MP – PG and N-MP – ethanol was studied. It has been shown that the efficacy of the antimicrobial preservative activity of N-MP and ethanol at a concentration of 25 % (w/w) exceeds the criteria A requirements against bacteria and fungi. 25 % propylene glycol solution has antimicrobial preservative effect on bacteria Pseudomonas aeruginosa (criteria A), Staphylococcus aureus (criteria B) and Escherichia coli (criteria B) as well as the yeast fungus Candida albicans (criteria A) and does not provide an effective preservative activity against fungus Aspergillus niger. 25 % aqueous solutions of hydrophilic solvents in respect to efficacy of antimicrobial activity descending can be positioned in such sequence: ethanol ≥ N-MP > PG. By reducing the content of N-MP to 15 % (w/w) the efficacy of antimicrobial preservative activity of its aqueous solution is not changed against bacteria and is reduced against fungi, in particular, to criteria В requirements in relation to A. niger. Combination N-MP and ethanol at concentrations of 15 % (w/w) and 25 % (w/w), respectively, as well as the combination N-MP and PG at the same concentrations ensures effective antimicrobial preservative activity of aqueous solutions, which exceeds greatly the criteria A requirements against bacteria and fungi. The solvent system NMP – ethanol is more efficient; synergism of the antimicrobial activity was observed for this system. The combination of N-MP and ethanol (96 %) at concentrations of 15 % (w/w) and 25 % (w/w) in gel based on carbomer as well as the combination of N-MP and PG at concentrations of 18 % (w/w) and 32 % (w/w) in cream-gel provided semi-solid preparations with an effective antimicrobial preservative activity, greatly exceeding the criteria A requirements. The further addition in the gel and the cream-gel of antimicrobial preservative phenoxyethanol at a concentration of 0.5 % had almost no impact on the efficacy of antimicrobial preservation. The research results indicate that the hydrophilic non-aqueous solvents used as cosolvents and permeation enhancers in semi-solid preparations with hydrophilic bases provide in certain concentrations and combinations effective antimicrobial preservation that allows to not add antimicrobial preservatives in such preparations as gels and cream-gels.
Keywords: efficacy of antimicrobial preservation, bacteria, fungi, hydrophilic non-aqueous solvent, a solution, a gel, a cream-gel.
Central laboratory of pharmaceutical development Farmak JSC, Kyiv
Qualitative composition selection of drug product in suspension for injection form based on betamethasone dipropionate and betamethasone sodium phosphate as drug substance
Using mathematical planning of experiment and multivariable dispersive analysis, qualitative composition selection of drug product in suspension for injection form based on betamethasone dipropionate and betamethasone sodium phosphate was done.
During researching the mathematical planning of experiment using 4×4 scheme of Graeco-Latin square of order 3 was done and studied the effect of 19 excipients that used the domestic and foreign pharmaceutical manufacturers within the development of finished drug products in the injection suspension forms.
Model solutions were studied regarding the main pharmaceutical technological quality properties: time for wetting of betamethasone dipropionate, suspension resuspendability, suspension stability time, viscosity, osmolality, the pH stability during storage. The research results of each quality parameters (response) were processed by analysis of variance. Using obtained results for the important factors did the assessment of exposure levels by Duncan test and built the comparison column charts for information.
The generalized indicator of quality — the desirability function was used for the confirmation of obtained results. Analysis of variance results that was obtained using the desirability function confirmed the choice of the best excipients. Experiments have established as the nature of the wetting agents, osmotic agents, buffer system components and suspending agents influence on the six quality parameters for the injectable suspension based on the combination of betamethasone dipropionate and betamethasone sodium phosphate. Taking into account the executed research results, the most appropriate excipients for the composition development of drug product in suspension for injection form based on the two esters of betamethasone were selected.
Keywords: suspension for injection, excipients, betamethasone dipropionate, betamethasone sodium phosphate, qualitative composition, mathematical planning, pharmaceutical factors, dispersive analysis.
Kolychev I.O., Koshovyi O.M., Zagayko A.L., Krasnikova T.O., Kovalyova A.M.
The National University of Pharmacy, Kharkiv, Ukraine
Prospects of the new hypoglycemic medicines creation on the basis of Bilberry leaves biologically active substances
In the dry extract from Bilberry leaves such groups of biological active substances were established as simple phenols, derivatives of hydroxycinnamic acids and flavonoids: coffeic, chlorogenic acids, rutin and kaempferol-3-O-glycosides. 15 phenolic substances were found by HPLC method. There were 8 hydroxycinnamic acids, 5 flavonoids, arbutin and nonidentified substance. The dominant substances are chlorogenic acid and rutin. 5 monosaccharides were identified in the dry extract. 31 organic acids were discovered and their quantitative content were determined by chromatography-mass-spectrometric method. The content of organic acids in the dry extract from the Bilberry leaves is 27.34 g/kg. 19 amino acids, 5 of which are indispensable — threonine, methionine, isoleucine, leucine, arginine were detected. The dominant compounds are glutamic acid, asparagine, serine, gamma-aminobutyric acid, leucine. The total content of amino acids before hydrolysis is 0.325 %, and after hydrolysis it increases to 0.93 %. The dry extract has a high content of flavonoids and hydroxycinnamic acids and adapted spectrophotometry methods will be used for its standardization. Hypoglycemic, hypolipidemic and antioxidant effects of the dry extract from Bilberry leaves were installed. The study of the chemical composition and pharmacological activity of the dry extract from the Blueberry leaves shows a prospect of creation a new drug with hypoglycemic activity.
Keywords: Blueberry, leaves, dry extract, hypoglycemic activity.
Azerbaijan Medical University, Baku
Research conducted on studying of the assortment in pharmacies in Republic of Azerbaijan
The article presents data on the results of research on studying of the assortment of pharmacies. The study was conducted at pharmacies, which are conditionally divided into 3 types — pharmacies, having the conditions for self-service (HCS), the pharmacies, having a little conditions for self-service (HLCS) and pharmacies that do not have the conditions for self-service (NHCS). It is considered expedient the following division of the assortment of pharmaceutical products: medicines, cosmetic products, hygiene products, baby products, items for nursing care and optical means. It was studied the populations attitude to the assortment of pharmacies and was found that they are most satisfied with the assortment of pharmacies with HCS (medicines — (76.6 ± 0.6) %, cosmetic products — (60.3 ± 0.7) %, hygiene products — (62.4 ± 0.7) %, baby products — (64.7 ± 0.7) %, items for nursing care and optical means — (72.5 ± 0.6) %). The largest proportion in the assortment of pharmacies with HCS, HLCS and NCS accounted on a share of medicines ((87.1 ± 0.4) % – (89.5 ± 0.3) %, (84.2 ± 0.5) % – (84.3 ± 0.5) %, (82.9 ± 0.6) % – (83.3 ± 0.6) %), items for nursing care and optical means ((6.2 ± 0.3) % – (5.4 ± 0.2) %, (8.8 ± 0.4) % – (7.4 ± 0.3) %, (9.7 ± 0.5) % – (9.5 ± 0.5) %).
Keywords: conditions for self-service, pharmacies, assortment,
pharmaceuticals, cosmetics, personal hygiene products.
Shapovalov V.V. (Jr.), Shapovalov V.V., Rogozhnikova O.V., Shapovalova V.О.
Kharkiv Medical Academy of Postgraduate Education
Department of Healthcare of Kharkiv Regional State Administration
Government principles regarding the improvement of medical provision on regional level for citizens affected by the Chernobyl disaster based on the pharmaceutical law
The article discusses the main disadvantages in the provision of privileged categories of citizens who have the status of victims of the Chernobyl disaster and receive benefits in accordance with the Law of Ukraine «On the status and social protection of citizens affected by the Chernobyl catastrophe» with the use of forensic and pharmaceutical practice. Analyzed legal documents of Ukraine concerning the provision of preferential categories of citizens affected by the Chernobyl disaster with necessary pharmaceutical care. Proposed the ways to improve medical support of these categories of preferential patients with the use of standards of pharmaceutical law, namely to develop an integrated and effective system of social guarantees for privileged categories of citizens; ensure transparency in the use of budget funds allocated for the provision of services to citizens on favorable terms; make the calculation of real need in the media regarding the above provision of medical contingent with individual approach to each patient, taking into account the level caused to the victim's physical, moral and material damage; continuously monitor the amount of preferential prescriptions by doctors (in districts of Kharkiv and Kharkiv region), which is not subsidized medicines released due to lack of adequate financial resources; taking into account the actual increase in the cost of medicines, which are guaranteed to get every Chernobyl disaster patient.
Keywords: medical provision, medicines, privileged categories of citizens, the liquidators of the Chernobyl accident affected by the Chernobyl disaster, pharmaceutical law.