МЕТОДОЛОГИЧЕСКИЙ ПОДХОД К ПЛАНИРОВАНИЮ ЭКСПЕРИМЕНТА ПРИ ВЫБОРЕ КАЧЕСТВЕННЫХ РЕАКЦИЙ ДЛЯ ПОДТВЕРЖДЕНИЯ ПОДЛИННОСТИ КОМПОНЕНТОВ ЛЕКАРСТВЕННОГО СРЕДСТВА (НА ПРИМЕРЕ АСКОРБИНОВОЙ КИСЛОТЫ)

The need for identification  testing of active substances or excipients in multi-component medicinal products,  including the use of qualitative tests, calls for research substantiating the choice of tests and test conditions  with due regard to interference  effects caused by other components  of medicinal products and the amount of the sample used. The aim of the study was to develop a methodological approach to designing experiments while selecting qualitative reactions for identification testing of a medicinal product component based on the results of studies investigating the possibility of using known qualitative tests (as illustrated by ascorbic acid in a multi-component product — 0.4 mg of ascorbic acid per 100 mg of the vial contents)  with due regard to interference on the part of other medicinal product components and the amount of the sample used. Material and methods: the study focused on a multi-component medicinal product — lyophilisate for solution for intravenous and intramuscular  injections containing an antiinflammatory active substance and ascorbic acid as a stabilizing agent (antioxidant). The analysis of literature sources helped to determine qualitative tests that were assessed for potential use for identification testing of ascorbic acid as a component of the analysed medicinal product. The study involved experimental testing of the qualitative reactions based on acidic and reducing properties of ascorbic acid. Results: it was demonstrated that several well-known qualitative tests could be used for identification  testing of ascorbic acid as a component of the analysed medicinal product,  namely, the reaction of ferrous ascorbate formation  and the reaction of silver nitrate reduction to metallic silver after preliminary separation of ascorbic acid from the other medicinal product components, as well as the reaction of Prussian blue formation,  iodine test and reaction with a potassium permanganate solution, which do not require additional sample preparation.  It is not practicable to use the reaction with a methylene blue solution and the Fehling’s reagent reaction for this particular medicinal product,  since their results are feeble. Conclusions: the analysis of the multi-component medicinal product helped to develop a methodological  approach to choosing qualitative reactions for identification testing of one of the medicinal product’s components  (e.g., ascorbic acid). The suggested algorithm includes the choice of reactions, determination of their sensitivity and applicability for a particular medicinal product, analysis of the other components’ effects on the results of the chemical reaction,  and the need for additional sample preparation.  The whole complex of the studies performed helped to determine qualitative reactions and optimal conditions for identification testing of the analysed substance.Необходимость подтверждения подлинности  действующих  или  вспомогательных веществ  многокомпонентных лекарственных средств,  в том числе с использованием качественных  реакций, влечет за собой  необходимость  проведения исследований по выбору реакций  и условий их проведения с учетом мешающего  влияния других компонентов лекарственного средства  и количества  используемого образца.  Цель работы: разработка  методологического подхода к планированию эксперимента при выборе  качественных  реакций  для подтверждения подлинности определяемого компонента лекарственного средства на основании результатов исследований возможности использования известных качественных  реакций  (на примере  аскорбиновой кислоты  в многокомпонентном лекарственном средстве — 0,4 мг аскорбиновой кислоты / 100 мг содержимого  флакона) с учетом мешающего влияния других компонентов лекарственного средства и количества  используемого образца.  Материалы и методы: в качестве  объекта исследования было выбрано  многокомпонентное лекарственное средство  — лиофилизат для приготовления раствора  для внутривенного и внутримышечного введения  с лекарственным веществом,  обладающим  противовоспалительным действием,  в состав которого  входит аскорбиновая кислота  в качестве  стабилизатора (антиоксиданта). В результате анализа  данных литературы  выбраны  качественные реакции  для проведения исследований возможности их использования для подтверждения  подлинности аскорбиновой кислоты  в изучаемом  лекарственном средстве.  Проведена  экспериментальная проверка  реакций, основанных на кислотных  и восстановительных свойствах аскорбиновой кислоты.  Результаты: установлено, что в изучаемом многокомпонентном лекарственном средстве для подтверждения подлинности аскорбиновой кислоты могут быть применимы несколько известных качественных реакций: реакции образования аскорбината железа и восстановления нитрата серебра до металлического серебра после предварительного отделения аскорбиновой кислоты  от других компонентов лекарственного средства,  а также реакция  образования берлинской лазури,  йодная проба и реакция  с раствором  перманганата калия,  не требующие  дополнительной пробоподготовки. Использование реакций  с раствором  метиленового  синего и реактивом  Фелинга  применительно к данному лекарственному средству нецелесообразно, так как результат указанных реакций  слабо выражен. Выводы: на примере многокомпонентного лекарственного средства разработан  методологический подход к выбору качественных  реакций  для подтверждения подлинности одного  из компонентов лекарственного средства  (например, аскорбиновой кислоты).  Алгоритм действий включает в себя выбор реакций, определение их чувствительности и целесообразности применения для конкретного лекарственного средства,  изучение  влияния других его компонентов на результат химической реакции, а также необходимость  или отсутствие дополнительной пробоподготовки. Совокупность проведенных  исследований позволяет сделать выбор качественных  реакций  и оптимальных  условий  их проведения для достижения поставленной цели — подтверждения подлинности определяемого вещества

Determination of visible particles in parenteral dosage forms and ophthalmic dosage forms

The present article describes the approaches to the choice of methods for assessing the content of visible particles in parenteral and ophthalmic dosage forms, recognized in general pharmacopoeia monograph «Visible particles in parenteral dosage forms and ophthalmic dosage forms», as well as a special approach to the assessment of visible particles in individual preparations according to the batch volume, package type, the amount of drug in a package, drug nature etc., requiring unusual conditions and evaluation criteria

A METHODOLOGICAL APPROACH TO DESIGNING EXPERIMENTS WHEN DEALING WITH IDENTIFICATION TESTS FOR MEDICINAL PRODUCT COMPONENTS (AS ILLUSTRATED BY ASCORBIC ACID)

The need for identification  testing of active substances or excipients in multi-component medicinal products,  including the use of qualitative tests, calls for research substantiating the choice of tests and test conditions  with due regard to interference  effects caused by other components  of medicinal products and the amount of the sample used. The aim of the study was to develop a methodological approach to designing experiments while selecting qualitative reactions for identification testing of a medicinal product component based on the results of studies investigating the possibility of using known qualitative tests (as illustrated by ascorbic acid in a multi-component product — 0.4 mg of ascorbic acid per 100 mg of the vial contents)  with due regard to interference on the part of other medicinal product components and the amount of the sample used. Material and methods: the study focused on a multi-component medicinal product — lyophilisate for solution for intravenous and intramuscular  injections containing an antiinflammatory active substance and ascorbic acid as a stabilizing agent (antioxidant). The analysis of literature sources helped to determine qualitative tests that were assessed for potential use for identification testing of ascorbic acid as a component of the analysed medicinal product. The study involved experimental testing of the qualitative reactions based on acidic and reducing properties of ascorbic acid. Results: it was demonstrated that several well-known qualitative tests could be used for identification  testing of ascorbic acid as a component of the analysed medicinal product,  namely, the reaction of ferrous ascorbate formation  and the reaction of silver nitrate reduction to metallic silver after preliminary separation of ascorbic acid from the other medicinal product components, as well as the reaction of Prussian blue formation,  iodine test and reaction with a potassium permanganate solution, which do not require additional sample preparation.  It is not practicable to use the reaction with a methylene blue solution and the Fehling’s reagent reaction for this particular medicinal product,  since their results are feeble. Conclusions: the analysis of the multi-component medicinal product helped to develop a methodological  approach to choosing qualitative reactions for identification testing of one of the medicinal product’s components  (e.g., ascorbic acid). The suggested algorithm includes the choice of reactions, determination of their sensitivity and applicability for a particular medicinal product, analysis of the other components’ effects on the results of the chemical reaction,  and the need for additional sample preparation.  The whole complex of the studies performed helped to determine qualitative reactions and optimal conditions for identification testing of the analysed substance

Определение видимых механических включений в лекарственных формах для парентерального применения и глазных лекарственных формах

The present article describes the approaches to the choice of methods for assessing the content of visible particles in parenteral and ophthalmic dosage forms, recognized in general pharmacopoeia monograph «Visible particles in parenteral dosage forms and ophthalmic dosage forms», as well as a special approach to the assessment of visible particles in individual preparations according to the batch volume, package type, the amount of drug in a package, drug nature etc., requiring unusual conditions and evaluation criteria.Описаны подходы к выбору методик оценки содержания видимых механических включений в парентеральных и глазных лекарственных формах, принятые в общей фармакопейной статье «Видимые механические включения в лекарственных формах для парентерального применения и глазных лекарственных формах», а также особый подход к оценке видимых механических включений в отдельных лекарственных препаратах в зависимости от объема серии, вида упаковки, объема препарата в упаковке, природы лекарственного средства и др., требующих нестандартных условий и критериев оценки

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos Dermatophytes: host-pathogen interaction and antifungal resistance

As micoses cutâneas estão entre as infecções mais comuns em humanos e se tornaram um importante problema de saúde pública, principalmente por causarem infecções invasivas em pacientes imunodeprimidos. Durante a infecção, a interação dermatófito-hospedeiro desencadeia adaptações metabólicas específicas que permitem aos patógenos aderirem e penetrarem no tecido, remodelando seu metabolismo para captar nutrientes e superar os mecanismos de defesa do hospedeiro. Esse remodelamento metabólico e a inter-relação entre metabolismo, morfogênese e resposta ao estresse são importantes fatores que estão sendo intensamente avaliados em diversos patógenos. As células do hospedeiro também respondem aos estímulos do patógeno, ativando vias de sinalização intracelular que culminam no desencadeamento de uma resposta imune contra o agente infeccioso. O entendimento molecular dessas respostas metabólicas pode ajudar no estabelecimento de novas estratégias terapêuticas. Nesta revisão, são abordados diferentes aspectos da biologia dos dermatófitos, com ênfase na interação dermatófito-hospedeiro e nos mecanismos de resistência a antifúngicos.<br>Cutaneous mycoses are among the most common infections in humans and have become an important public health issue because they cause invasive infections in immunocompromised patients. During the infectious process, dermatophyte-host interactions trigger specific metabolic adaptations that allow the pathogen to adhere to and penetrate the host tissue, scavenge nutrients, and overcome the host defense mechanisms. This metabolic shift and the interplay between metabolism, morphogenesis and stress response are important factors that have been extensively studied in several pathogens. Host cells also respond to the pathogen stimuli by activating intracellular signaling pathways that trigger the immune response against the infectious agent. The comprehension of the molecular aspects of these responses may help to establish new therapeutical strategies. In this review, different aspects of the biology of dermatophytes are addressed, with emphasis on the dermatophyte-host interaction and the mechanisms of antifungal resistance