The thermogravimetric study of the ointment with the water-soluble proteinpolysaccharide complex of Pleurotus ostreatus

The manufacturing process for soft dosage forms is always accompanied by the action of a certain temperature, which violation can lead not only to the deterioration of technological indicators, but also significantly affect the pharmacological activity of the finished drug.Aim. To study the water-soluble protein-polysaccharide complex (WSPPC) of Pleurotus ostreatus (oyster mushroom) and the ointment composition developed on its basis using thermogravimetry.Materials and methods. The thermogravimetric analysis, which allowed determining the change of the mass of the test sample under the conditions of the controlled temperature rise, was chosen as the research method. Determination of thermogravimetric characteristics was performed using a Q-1500 D derivatograph of the “F. Paulik, J. Paulik, L. Erdey” system with a platinum-platinum-rhodium thermocouple when heating samples 30 to 250 °C.Results and discussion. In the course of the thermogravimetric study it has been determined that WSPPC and the ointment composition developed on its basis have physical transformations at certain temperatures. The presence of thermal effects on the thermogram of the ointment developed coincides with the thermal effects of WSPPC; and it subjectively indicates the absence of the chemical interaction between the active pharmaceutical ingredient and the excipients of the carrier base.Conclusions. Based on the results obtained the optimal conditions of the temperature regime for the manufacturing process have been determined. They will provide the stability of the physicochemical properties and the pharmacological effect of the finished ointment.

Implementation of the Quality by Design approach for developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction

Aim. To implement the Quality by Design (QbD) approach in order to develop the composition and the manufacturing technology of injectable hyaluronate sodium (HS) in combination with chondroitin sulfate (CS) for intra-articularintroduction. Materials and methods. The composition of the solution for injection was developed using samples of the active pharmaceutical ingredient (API) of HS and CS. The approaches of the ICH international guidelines were used to create the QbD protocol. The quality target product profile (QTPP) was developed based on the literature review, analysis of similar drugs and the previous in-house experimental studies. Determination of critical quality assessment (CQA) product indicators was performed by risk analysis for all quality indicators listed in QTPP. The risk assessment of quality indicators was performed by assessing them according to the Risk Priority Number system (hereinafter – RPN) by a 9-point scale. When studying the composition and the manufacturing technology of the injectable solution the quality risk management (QRM) was developed according to the Ishikawa diagram. Results and discussion. It has been found that the QbD concept is a systematic approach to the drug development. At the first stage QTPP was developed. Based on the QTPP data the CQA indicators were determined, and quality risks were assessed. The critical process parameters (CPP) of the solution for injection based on HS and CS, their control methods, as well as the critical material attributes (CMA) were determined. Based on the data obtained the drug control strategy was proposed taking into account the need to minimize the repetition of control experiments. Using the Isikawa diagram the variability of the material and the process with the environmental factors affecting the qualityof the solution for injection with HS and CS was shown.Conclusions. Using the basic QbD approaches when developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction it has been found that the route of administration, dose, potency, and consumer properties of the product are important aspects of QTPP. It has been proven that the quality indicators, such as transparency, viscosity, sterility and the quantitative content of API are determined as CQA to achieve the objectives defined in QTPP. The study shows that almost all stages of production are critical, therefore, they need to be constantly monitored and checked to obtain a quality product. In further experimental studies to confirm the composition developed and the manufacturing technology according to QRM it is necessary to focus on such indicators as the solution temperature, stabilization time, degassing mode and filtration conditions.

Some issues for implementing the requirements for good practices (GxP). Good distribution practice (GDP) (Part 2)

Aim. To conduct a detailed study of the requirements of good distribution practice. Materials and methods. The analysis of the current Guidelines on good practices (GxP), in particular the Guideline ST-N 42-5.0:2014 of the Ministry of Health of Ukraine “Medicines. Good Distribution Practice” was performed. Interpretations for the implementation of the requirements of good distribution practice based on the experience of audits of distribution companies for GDP compliance with the requirements were proposed. Results and discussion. The dependence of the correct distribution of medicines on the personnel involved in this process has been studied, and the negative impact on the activity of a wholesale pharmaceutical company in case of non-compliance by the personnel with the relevant requirements has been determined. The benefits and risks that may arise during the distribution of medicines related to the staff have been identified. The requirements for the Authorized (Responsible) Person, the knowledge and experience that he must possess have been determined. The job description of the Authorized (Responsible) Person has been considered in detail. The responsibilities of the Authorized Person of a distribution company are listed. Conclusions. The detailed analysis proposed will minimize the risks and errors that can lead to a negative impact on the quality of medicines. The appointment of the Authorized Person of a distribution company, the requirements imposed on him, the knowledge and experience that the Authorized Person must possess have been studied in detail. The advantages and risks of the personnel management of a distribution company have been identified.

Potentiometric determination of organic acids in the medicinal plant raw material

Aim. To analyze the results of the quantitative content of the amount of organic acids in rhizomes with roots of Rumex confertus, rhizomes with roots of Sanguisorba officinalis, roots of Rosa majalis and roots of Rosa canina, roots of Arctium minus and roots of Arctium tomentosum, herb of Bidens tripartite by the potentiometric method, which is available in the monograph “Hibiscus” in the SPhU 2.0. Materials and methods. The study subjects were batches of rhizomes with roots of Rumex confertus, rhizomes with roots of Sanguisorba officinalis, roots of Rosa majalis and roots of Rosa canina, roots of Arctium minus and roots of Arctium tomentosum, herb of Bidens tripartite. The quantitative content of the amount of organic acids was determined by the potentiometric method from the monograph “Hibiscus” SPhU 2.0 using a HI 2550 potentiometer of the “HANNA instruments” company (Germany). Results and discussion. The highest content of the amount of organic acids, among the study subjects was in roots of Arctium minus (from 1.02 ± 0.04 % to 1.05 ± 0.04 %). At the same time, in roots of Arctium tomentosum this amount was almost 3 times lower (from 0.36 ± 0.01 % to 0.37 ± 0.01 %). In the batches of roots of Rosa majalis the content of this group of compounds was almost 2 times higher than in roots of Rosa canina. In rhizomes with roots of Rumex confertus and rhizomes with roots of Sanguisorba officinalis the content of the amount of organic acids differed insignificantly. In herb of Bidens tripartite the content of this group of compounds was 0.78 ± 0.03 – 0.79 ± 0.03 %. In different batches of one type of the raw material the quantitative content of the amount of organic acids varied slightly. Conclusions. For the first time, the quantitative content of the amount of organic acids has been determined in the batches of rhizomes with roots of Rumex confertus, rhizomes with roots of Sanguisorba officinalis, roots of Rosa majalis and roots of Rosa canina, roots of Arctium minus and roots of Arctium tomentosum, herb of Bidens tripartite using the potentiometric method which is available in the monograph “Hibiscus” in the SPhU 2.0. It has been found that the highest content of the amount of organic acids is observed in roots of Arctium minus (not less than 1.02 %) and herb of Bidens tripartite (not less than 0.78 %). The results obtained will be used in further research when creating new herbal medicines with the anti-inflammatory and antimicrobial activity.

Development of methods for analysis of the amount of flavonoids and their stability study in the combined dental gel

An important aspect in the pharmaceutical development of dental medicines is to provide them with a prolonged therapeutic effect while reducing the side effects of drug substances and the possibility of long-term use. This can be achieved by using active components of plant origin. Aim. To develop methods for analyzing biologically active substances in the composition of a new combined dental gel. Materials and methods. The study object was a dental gel containing “Phytodent” complex tincture (PJSC “CPP Chervona zirka”, Ukraine). Based on the analysis of the composition of the tincture it was proposed to carry out standardization by the amount of biologically active substances, namely flavonoids. Identification was carried out by TLC, while the quantitative determination by absorption spectrophotometry, the ultraviolet and visible method by the reaction with aluminum chloride using the standard method calculated with reference to rutin and the absorbance measurement at 406 nm. Results and discussion. As a result of the research, the methods for the analysis of flavonoids in the composition of the new combined gel have been developed. The spectrophotometric method developed is characterized by specificity, accuracy, precision and linearity with r = 0.9998. One of the important issues when using components of plant origin is their stability both during preparation and storage. Using the method developed the stability of flavonoids has been studied depending on pH changes of the carbomer-based dental gel. Conclusions. It has been determined that the methods developed are easily reproducible and allow to identifying and quantifying flavonoids in the dental gel. It has been found that a stable content of flavonoids is characteristic of the carbomer-based gel neutralized to pH values from 5.0 to 6.0.

The study of medication adherence in patients with arterial hypertension in the practice of a family doctor

The treatment of arterial hypertension (AH) is one of the most significant problems of modern internal medicine. Elevated blood pressure (BP) is a major risk factor for atherosclerosis, mainly coronary heart disease and damage tothe brain vessels. Medication adherence (MA) is a complex problem in patients with chronic cardiovascular diseases, especially AH.Aim. To study MA when treating patients with AH in a real Ukrainian out-patient practice for 8 weeks.Materials and methods. The sample of 274 patients with AH included men and women over 18 years old with the initial level of office systolic blood pressure (SBP) of 140-179 mm Hg and diastolic blood pressure (DBP) of 99-100 mm Hg against the background of the antihypertensive therapy or without it. Initially, BP was measured at the doctor’s office (office blood pressure) in all patients who were enrolled in the study; the body mass index (BMI), as well as risk factors were calculated, and the concomitant therapy was assessed. The quality of life was determined by a visual analog scale (VAS score). Patient adherence to the drug therapy was evaluated using the Morisky Medication Adherence Scale (MMAS).Results and discussion. To conduct the study according the MMAS test all patients were distributed in two groups with low MA (MMAS = 3 or 4, n = 181) or high MA (MMAS ≤ 2, n = 93) by the psychometric scale. The results of the MMAS test obtained were confirmed by the reliability parameter used in psychometrics (Cronbach’s Alpha ˃ 0.7). It was found at the end of the study that BP levels less than 140/90 mm Hg of 50.6 % of the Low MA group patients and 47.7 % of the High MA group patients were reached. A decrease in SBP < 140 mm Hg or a decrease in 20 mm Hg and more from the initial level, as well as a decrease in DBP < 90 mm Hg or 10 mm Hg and more was observed in 98.8% of patients in the Low MA group and in 98.4 % in the High MA group. After 8 weeks of observation, the quality of life significantly improved in both groups; however, in the Low MA group this improvement was more pronounced – more than 85 points instead of 82.8 by the VAS scores for the High MA group.Conclusions. The effectiveness of the AH treatment and achievement in the target BP level depend on the patient’s MA. Regular visits to the family doctor’s clinic mobilize patients, and are one of the factors that increase adherence to the treatment, along with pharmaceutical care.

The analysis of the drug assortment of immunostimulants presented at the Ukrainian market

Aim. To analyze the registered medicines of the group of immunostimulants in order to determine the feasibility of creating and organizing the production of new drugs based on natural clays, in particular green and yellow clays.Materials and methods. The list of medicinal products compiled from official sources of information was used in the work; it was processed by the methods of generalization, systematization, graphical method, as well as the methods of comparative and structural analysis.Results and its discussion. The analysis of the Ukrainian pharmaceutical market concerning the range of the registered immunostimulants has been performed. Structuring of the selected list of medicines by the ATC-classification, origin, composition, production characteristic and dosage form type has been carried out. By production basis the majority of medicines are of domestic production (63.58 %). It has been determined that drugs of the segment studied are produced in solid and liquid dosage forms. Solutions for injection are prevalent at the domestic pharmaceutical market, and the range of solid dosage forms is under developed. At the pharmaceutical market, there are no drugs of this group with natural clays, in particular yellow and green clays.Conclusions. The absence of immunostimulants based on natural clays at the Ukrainian market has been proven; it indicates the feasibility of introducing new domestic drugs with the immunostimulating action on the basis of natural clays, in particular yellow and green clays, to the market.

The current state and prospects of the development of soft dosage forms with Boraginaceae species

Soft dosage forms make up a significant segment in the structure of medicines both pharmaceutical and industrial production. Herbal ointments are an integral part of this group. Species of the Boraginaceae family are the source of biologically active substances used to treat inflammatory processes of all layers of the skin, muscle tissue, tendons and joints.Aim. To determine data on the current state of the development of soft dosage forms based on species of the Boraginaceae family and identify further prospects for studies in this area.Materials and methods. The scientific databases, in particular Abdata Pharma-Daten-Service, BioMed Central, Scopus, scientific periodicals of Ukraine – Vernadsky National Library of Ukraine, etc., were analyzed.Results and discussion. As a result of the data analysis of the Information Fund “State Register of Medicines of Ukraine” it has been found that only medicines with comfrey (Symphytum officinale L.) are registered in Ukraine. In the EU countries, only soft dosage forms with comfrey are registered, with the exception of Greece where there are ointments with Alkanna tinctoria (L.) Taush, and France where there are substances for the production of ointments withPulmonaria obscura Dumort. and Anchusa officinalis L. There are many soft homeopathic dosage forms with comfrey at the US pharmaceutical market; however, there are ointments and suppositories with Borago officinalis L. and a gel with Myosotis arvensis (L.) Hill. At the Brazilian pharmaceutical market there is the cream “Acheflan” based on Cordia verbenacea DC. The European and Asian scientists study ointments with Cordia myxa L., Cordia obliqua Willd., Heliotropium indicum L., Arnebia euchroma Rolye. (Johnst.), Onosma dichroanthum Boiss, Arnebia densiflora (Nordm.) Ledeb, Ehretia microphylla Lam., Anchusa officinalis L.Conclusions. Homeopathic products predominate among the soft dosage forms based on Boraginaceae species. At the pharmaceutical market, along with comfrey drugs, there are medicines and active substances with Borago officinalis, Myosotis arvensis (L.) Hill, Alkanna tinctoria (L.) Taush, Pulmonaria obscura Dumort., Anchusa officinalis L. and Cordia verbenacea DC. There is an active research of the existing products with comfrey, as well as the development and study of new soft dosage forms with species of Arnebia, Heliotropium, Cordia, Onosma, Ehretia and Anchusa genus. Taking the above into account the further research for creating effective and safe drugs based on the Boraginaceae species is promising.

The development of the conditions for vortioxetine isolation from biological fluids

The chemical-toxicological significance of antidepressant drugs is steadily increasing. The development of effective methods of the sample preparation of the biological material is an important analytical aspect in toxicology of the newgeneration antidepressants. Aim. To develop the conditions for the sample preparation of biological fluids in order use them in the chemicaltoxicological analysis of the new antidepressant vortioxetine. Materials and methods. The studies were performed with model blood and urine samples spiked with vortioxetine. When examining the blood the formed blood elements were pre-precipitated by adding 10 % solution of trichloroacetic acid. The extraction purification was performed with hexane at pH 1-2, and the drug was extracted from the biologicalfluids with methylene chloride at pH 8-9. The extracts obtained were further subjected to TLC purification. Vortioxetine in eluates from chromatograms was determined by the UV-spectrophotometric method. Results and discussion. The Rf value of vortioxetine in the mobile phase of ethyl acetate-methanol-25 % ammonium hydroxide solution (85 : 10 : 5) was 0.77 ± 0.05. The UV spectra of the eluates from the chromatograms had absorption maxima at the wavelengths of 229 ± 2 and 232 ± 2 nm and matched with the UV spectrum of the standard solution of vortioxetine in methanol. The quantitative determination was performed at λmax232 nm by the equation of the calibration curve y = (0.0172 ± 3 · 10-4)x + (0.027 ± 0.008). Under the conditions of the sample preparation developed 27 ± 1 % of vortioxetine from the blood and 62 ± 2 % of the drug from the urine were isolated. Conclusions. The efficiency of the sample preparation of biological fluids by the method of liquid-liquid extraction in relation to the new antidepressant vortioxetine has been determined. The methods developed are recommended for use in forensic and clinical toxicology.

Features of teaching the fundamental and optional subjects to foreign applicants for higher education at the Department of Microbiology, Virology and Immunology of the National University of Pharmacy

Aim. To generalize the experience in teaching the fundamental and optional subjects at the Department of Microbiology, Virology and Immunology, find new methodological and pedagogical techniques in order to optimize the assimilation of basic medical concepts and skills among foreign applicants for higher education. Materials and methods. Within the framework of this study the modern data on methods and aids in teaching were studied, approaches to teaching the disciplines of the biomedical profile, such as “Microbiology with the basics of immunology” as a fundamental subject, and disciplines “Epidemiology of diseases” and “Tropical infections” as optionalsubjects for foreign applicants for higher education at the Department of Microbiology, Virology and Immunology of the National University of Pharmacy were systematized and analyzed. Results and discussion. The discipline “Microbiology with the basics of immunology” refers to the fundamental disciplines of the biomedical profile, which is studied by foreign applicants for higher education of the pharmaceutical faculty. At the Department of Microbiology, Virology and Immunology of the National University of Pharmacy various modern methodological techniques are used when conducting lectures, practical classes and seminars. In the educational process modern methods of teaching, monitoring and assessing knowledge are widely used in the form of a computer survey that involves foreign students in the process of mastering computer technologies aimed at forming their knowledge;it helps to successfully solve educational problems within the classroom setting. The widespread use of the test control of knowledge is an important means of increasing the effectiveness of the educational process. The inclusion of interactive forms in the educational process relieves the nervous load of students, makes it possible to change the forms of activity, switch attention to the key issues of the topic of the lessons. It is also ethodologically interesting to conduct practical classes in the form of a discussion abstract conference, as well as the use of role-playing games. All this allows an objective assessment of the student’s preparation for the lesson, develops communication skills, creative thinking, an active life position, the ability to formulate thoughts using professional terms, forms public speaking skills, forms stereotypes of professional behavior and their correction in communication. Conclusions. In recent years, the Ukrainian education system has been undergoing modernization of the learning process. Constant changes open up the need for each teacher to search for such pedagogical technologies that will motivate students, will make them interested in studying the discipline. This is especially true for such a category of students as foreign students. Thus, for the successful formation of effective educational activities of foreign students it is necessary to have modern educational and methodological literature, creative organization of the students’ independent work aimed at the wide use of active teaching methods (group discussions, business games), the effective work with information, setting and solving scientific practical problems, the participation of teachers and students in joint research work.