Origin, development, and modern application value of Chinese herbal lozenges / 中国中药杂志

Lozenge is one of the traditional dosage forms of Chinese medicine. It has been recorded in traditional Chinese medical classics of all dynasties since the Eastern Han Dynasty and has been developing and evolving continuously. The unique pharmaceutical methods and application scope are the driving force of its emergence, existence, and development. Up to now, lozenge has been included in the Chinese Pharmacopoeia as an independent dosage form. Lozenge has been endowed with new meaning by modern Chinese medicine pharmaceutics, which is worth tracing origin and exploring value. The present study reviewed the origin and development of lozenge, compared lozenge with other similar dosage forms, analyzed the characteristics of modern and ancient dosage forms of lozenge, and discussed the development prospect and potential of lozenge in combination with the demand development of modern Chinese medicine preparation, so as to provide references for expanding the modern application of lozenge.

Desenvolvimento de rota sintética da Rosiglitazona em processo batelada e microrreator capilar / Rosiglitazone synthetic route development in batch process and capillary microreactor

Para que os fármacos possam ser comercializados economicamente, a sua escala de produção deve ser aumentada para atender à demanda do mercado. Atualmente, a maior parte dos fármacos são sintetizados em processos batelada que possuem limitações quanto à eficiência de mistura, temperatura e pressão. O uso de microrreatores surge como alternativa na indústria químico-farmacêutica, aumentando a eficiência dos processos de maneira segura. Ferramentas utilizadas no segmento computacional multidisciplinar teórico, como o DFT (Density Functional Theory), podem prever e compreender o comportamento das reações químicas, podendo ter grande utilidade na síntese de novos fármacos economizando tempo, investimento e reduzindo a geração de resíduos. A diabetes mellitus é uma doença de caráter epidêmico, que a cada ano vem aumentando o número de casos. O emprego de fármacos derivados das glitazonas no tratamento de diabetes mellitus tipo 2 é recomendado devido ao excelente controle glicêmico que esta classe de fármacos oferece. Neste trabalho, foi sintetizada a Rosiglitazona, um fármaco derivado das glitazonas, que auxilia no tratamento da diabetes mellitus tipo 2, sendo estudadas duas rotas de síntese distintas, que foram otimizadas com o intuito de maximizar o rendimento de seus intermediários, obtendo a Rosiglitazona com pureza de cerca de 94%. Foi realizada, para os intermediários, aqui denominados, 1R, 2R2 e 3R2 a síntese one-pot e para os intermediários 1R, 2R1 e 3R2 foi realizada a transposição do processo usual em batelada para fluxo contínuo no microrreator, com rendimentos de até 93%. Com o auxílio da química quântica computacional, a reação de síntese do intermediário 1R, foi elucidada teoricamente e determinadas as grandezas termodinâmicas (ΔH‡, ΔG‡ e ΔS‡) no estado de transição, que foram comparadas com os valores experimentais, sendo constatada uma boa concordância, com desvio máximo de 14%

In order for drugs to be commercialized economically, their production scale must be increased to meet market demand. Currently, most drugs are synthesized in batch processes that have limitations in terms of mixing efficiency, temperature and pressure. The use of microreactors appears as an alternative in the chemical-pharmaceutical industry, increasing the efficiency of the synthesis processes in a safe way. Tools used in the theoretical multidisciplinary computational segment, such as DFT (Density Functional Theory), can predict and understand the behavior of chemical reactions, and can be very useful in the synthesis of new drugs, saving time, investment and reducing waste generation. Diabetes mellitus is an epidemic disease that has been increasing the number of cases every year. The use of drugs derived from glitazones in the treatment of type 2 diabetes mellitus is recommended due to the excellent glycemic control that this class of drugs offers. In this work, Rosiglitazone, a drug derived from glitazones, which helps in the treatment of type 2 diabetes mellitus, was synthesized. Two different synthetic routes were studied and optimized in order to maximize the yield of its intermediates, obtaining Rosiglitazone with purity of about 94%. One-pot synthesis was performed to 1R, 2R2 and 3R2 intermediates, and the transposition from the usual batch process to continuous flow in microreactor was performed to 1R, 2R1 and 3R2 intermediates, with yields of up to 93%. With the aid of computational quantum chemistry, the intermediate 1R synthesis reaction was theoretically elucidated and the thermodynamic properties were determined (ΔH‡, ΔG‡ and ΔS‡) in the transition state, which were compared with the experimental results, obtaining good agreement, with a maximum deviation of 14%

Erding formula and bioactive markers in hyperuricemia: towards rational scientific approaches for the modernization of Traditional Chinese Medicine

Introduction: Traditional Chinese Medicine (TCM) represents one of the first holistic approaches in the world to treat and prevent disease. Herbal medicine is one of the major therapeutic remedy in TCM. It often involves multi-herb therapies instead of single herb preparations. Parallel to western medicine, hundreds of herbal formulas have been made available as finished products. Currently, the use of herbal products is popular as treatment option or to complement western medicine. Indications of the herbal formulas were established by TCM terms such as heat-clearing and/or detoxifying which lack modern pharmacological meanings. It is difficult for people without relevant background to understand such terms and their implications for treatments. Furthermore, due to the quality control issues of herbal medicines which contain multiple constituents, consumers may be confronted with the risk of using unstandardized products. Hence, in this thesis, the modernization of TCM is discussed through employing scientific pharmaceutical approaches to a traditional formula, called Erding formula (EF). The aim was to investigate if a new indication, hyperuricemia, can be assigned to a heat-clearing and detoxifying formula. Our hypothesis was: Can Erding formula be used for hyperuricemia treatment and is esculetin a bioactive marker for this new indication? Methods: A hypoxanthine and potassium oxonateinduced hyperuricemic mouse model, a xyleneinduced inflammatory mouse model, and an acetic acidinduced pain model were used to investigate EF and its constituent herbs. The quantity of esculetin was measured by high-performance liquid chromatography. The therapeutic effect of esculetin was assessed using potassium oxonate induced hyperuricemic mouse model, and esculetin and its metabolites were characterized in serum via ultra-performance liquid chromatographyquadrupole time-of-flight mass spectrometry. To develop a modern dosage form, a laboratory-scale wet bead milling approach was employed to prepare esculetin nanocrystals. The formulation was further optimized by design of experiment, and an optimized formulation was then characterized for its saturation solubility and short-term stability. Results: The study showed that EF and Viola yedoensis Makino (Viola) lowered uric acid (UA) levels, while EF and all four individual herbs had antiinflammatory and analgesic activities. These findings revealed that EF was able to treat hyperuricemia and suggested that Viola was the main herb in EF on reducing UA levels. The study showed that esculetin significantly reduced UA levels and six metabolites of esculetin were identified in serum. This confirms that esculetin was absorbed and is a suitable bioactive and quality control marker for EF in hyperuricemia treatment. An esculetin-Povacoat nanocrystal formulation with a 200 nm particle size was successfully prepared. The formulation presented up to a 1.5-fold increase in saturation solubility compared to the bulk esculetin and it was stable for 180 days. Conclusion: The studies proved that Erding formula can be used for hyperuricemia treatment with esculetin as bioactive quality control marker. As well, a new nano-sized formulation of the bioactive marker, esculetin, was created. This presented the possibility to develop an innovative nanotechnological product of the active substances derived from herbal medicine. The findings facilitated a better understanding of TCM terms and concept through mechanistic scientific experiments. This study revealed a potential pathway and an idea to modernize TCM without setting aside its unique concepts. This might increase the global acceptance of TCM products. Furthermore, the TCM concept might be useful in the development of multi-component drug products

Medicina Tradicional Chinesa (MTC) representa uma das primeiras abordagens holísticas em âmbito global para tratar e prevenir doenças. A fitoterapia consiste na principal terapia na MTC. Frequentemente, envolve terapias com múltiplas ervas em vez de preparações individuais. Paralelamente à medicina ocidental, centenas de fórmulas herbais foram disponibilizadas como produtos acabados. Atualmente, o uso de produtos fitoterápicos é popular como opção de tratamento ou para complementar a medicina ocidental. As indicações das fórmulas fitoterápicas foram estabelecidas pelos termos da MTC, tais como "limpeza pelo calor e / ou desintoxicante", que não têm significados farmacológicos modernos. É difícil para a população em geral e mesmo para profissionais sem histórico relevante na área entender tais termos e suas implicações para os tratamentos. Além disso, devido às questões de controle de qualidade dos medicamentos fitoterápicos que contêm múltiplos constituintes, os pacientes podem ser confrontados com o risco de usar produtos não padronizados. Assim, nessa tese, a modernização da MTC é discutida por meio da utilização de abordagens farmacêuticas científicas para uma fórmula tradicional, denominada fórmula de Erding (FE). O objetivo foi o de investigar se uma nova indicação, a hiperuricemia, pode ser atribuída a uma fórmula desintoxicante e de compensação de calor. Nossa hipótese foi: a fórmula de Erding pode ser usada para tratamento de hiperuricemia e a esculetina é um marcador bioativo para essa nova indicação? Foi empregado modelo de camundongo hiperuricêmico induzido por hipoxantina e oxonato de potássio, outro modelo de camundongo inflamatório induzido por xileno e, adicionalmente, modelo de dor induzida por ácido acético. Esses modelos foram usados para investigar a FE e suas ervas constituintes. A quantidade de esculetina foi determinada por cromatografia líquida de alta eficiência. O efeito terapêutico da esculetina foi avaliado utilizando modelo de camundongo hiperuricêmico induzido por oxonato de potássio, e a esculetina e seus metabólitos foram caracterizados no soro por cromatografia líquida de alto desempenho - espectrometria de massa. Para desenvolver forma farmacêutica moderna, uma abordagem de moagem em escala úmida reduzida foi empregada tendo em vista a preparação de nanocristais de esculetina. A formulação foi ainda otimizada empregado planejamento experimental. Essa fórmula foi caracterizada quanto à sua solubilidade de saturação e estabilidade a curto prazo. O estudo mostrou que a FE e a Viola yedoensis Makino (Viola) reduziram os níveis de ácido úrico (AU), enquanto a FE e as quatro plantas individuais apresentaram atividades antiinflamatória e analgésica. Esses resultados revelaram que a FE foi capaz de tratar a hiperuricemia e sugeriu que a viola foi a principal erva da FE na redução dos níveis de AU. O estudo mostrou também que a esculetina reduziu significativamente os níveis de AU e os seis metabólitos da esculetina foram identificados no soro. Tal resultado confirma que a esculetina foi absorvida e pode ser usada como marcador de controle bioativo e de qualidade para FE, no tratamento da hiperuricemia. A formulação de nanocristais de esculetin-povacoat® apresentou tamanho de partícula de 200 nm. A formulação apresentou aumento de 1,5 vezes na solubilidade de saturação em comparação com a esculetina em escala micrométrica e manteve-se estável durante 180 dias. Os estudos comprovaram que a fórmula de Erding pode ser utilizada no tratamento da hiperuricemia empregando a esculetina como marcador bioativo de controle de qualidade. Além disso, foi desenvolvida formulação inovadora, em escala nanométrica, do marcador bioativo, a esculetina. Esse resultado permitiu desenvolver produto com base nanotecnológica das substâncias ativas derivadas do fitoterápico, assim comol permitiram melhor compreensão dos termos e dos conceitos da MTC por meio de experimentos científicos mecanicistas. Esse estudo revelou potencial para a modernização da MTC sem excluir seus conceitos únicos. Isso pode aumentar a aceitação global dos produtos MTC. Além disso, o conceito de MTC pode ser útil no desenvolvimento de medicamentos de múltiplos componentes

Estudo da permeabilidade de fármacos por meio do modelo de saco intestinal de ratos / Study of drug permeability through the rat gut sac model

Os parâmetros de permeabilidade e solubilidade são fundamentais à absorção oral de fármacos e a partir dessas características, foi criado o Sistema de Classificação Biofarmacêutica, através do qual os fármacos são divididos em quatro classes. Atualmente, para a determinação da solubilidade de um fármaco, existem diversos métodos padronizados por agências regulatórias, no entanto, para a determinação da permeabilidade, os ensaios são passíveis de diversas variações em sua execução, diminuindo a confiabilidade dos resultados obtidos e impossibilitando a comparação dos mesmos quando realizados com técnicas diferentes umas das outras. O objetivo do presente trabalho é avaliar as variáveis experimentais do modelo do saco intestinal que podem influenciar nos resultados de permeabilidade aparente de fármacos e na viabilidade do tecido. O presente estudo foi aprovado pelo Comitê de Ética no Uso de Animais da FCF-USP (109.2018-P574). Foram utilizados 33 Rattus norvegicus da linhagem Wistar, machos, jovens adultos, com peso entre 200 g e 300 g. Para realização do procedimento, cada animal permaneceu em jejum por cerca de quatro horas e após adequada anestesia a porção do jejuno do intestino delgado foi retirada e dividida em seis segmentos de aproximadamente 8,5cm cada. Foram realizados experimentos com e sem inversão do saco intestinal, submetidos a diferentes tempos de banho de gelo após sua ressecção, na presença ou ausência de inibidor da glicoproteína-P (verapamil). Os fármacos naproxeno e famotidina foram empregados como marcadores de alta e baixa permeabilidade, respectivamente. A losartana foi utilizada como substrato da glicoproteína P. Cada um dos sacos intestinais foi colocado em um tubo de ensaio contendo tampão Krebs, a 37°C, saturado com gás carbogênio. Para avaliação da integridade e viabilidade dos segmentos intestinais, observou-se a presença de movimentos peristálticos e coletaram-se amostras do meio de incubação nos tempos 0, 30, 45, 60, 90 e 120 minutos para quantificação dos fármacos e de glicose, uma vez que esta é ativamente transportada para a serosa do intestino delgado. Determinou-se a permeabilidade aparente de cada fármaco e as concentrações de glicose nas diferentes condições experimentais, realizou-se planejamento fatorial multinível e os resultados foram analisados por análise variância (ANOVA), seguida de pós-teste de Tukey. Observou-se que as variáveis experimentais interferiram de forma significativa na viabilidade tecidual e na permeabilidade aparente dos fármacos. Não foram observadas diferenças significativas da permeabilidade de fármacos nos diferentes segmentos do jejuno. A glicose mostrou-se um bom marcador de viabilidade tecidual e foi constatado que a presença ou ausência de movimentos peristálticos não está relacionada diretamente com a viabilidade do tecido. Uma vez que foram constatadas tantas interferências nos resultados, é imprescindível que os procedimentos experimentais sejam padronizados, para que os resultados apresentem menor variabilidade e possam ser comparados entre si

The permeability and solubility parameters are fundamental to the oral absorption of drugs and from these characteristics, the Biopharmaceutical Classification System was created, through which drugs are divided into four classes. Currently, for the determination of the solubility of a drug, there are several methods standardized by regulatory agencies, however, for the determination of permeability, the tests are subject to several variations in their execution, reducing the reliability of the results obtained and making it impossible to compare the results obtained. same when performed with different techniques. The aim of this study is to evaluate if different experimental conditions can influence the results of apparent drug permeability and tissue viability on gut sac model. The present study was approved by the Ethics Committee for the Use of Animals of FCF-USP (109.2018-P574). Thirty-three male, young adult Rattus norvegicus were used, weighing between 200 g and 300 g. To perform the procedure, each animal fasted for about four hours and after adequate anesthesia, the portion of the jejunum of the small intestine was removed and divided into six segments of approximately 8.5 cm each. Experiments were performed with and without inversion of the gut sac, submitted to different times of ice bath after its resection, in the presence or absence of a P-glycoprotein inhibitor (verapamil). The drugs naproxen and famotidine were used as markers of high and low permeability, respectively. Losartan was used as a substrate for P-glycoprotein. Each of the gut sacs was placed in a test tube containing Krebs buffer, at 37°C, saturated with carbogen gas. To evaluate the integrity and viability of the intestinal segments, the presence of peristaltic movements was observed and samples of the incubation medium were collected at 0, 30, 45, 60, 90 and 120 minutes for quantification of drugs and glucose, as it is actively transported to the serosa of the small intestine. The apparent permeability of each drug and the glucose concentrations were determined under different experimental conditions, multilevel factorial design was performed and the results were analyzed by analysis of variance (ANOVA), followed by Tukey's post-test. It was observed that the experimental variables significantly interfered in the tissue viability and in the apparent permeability of the drugs. No significant differences in drug permeability were observed in the different segments of the jejunum. Glucose proved to be a good marker of tissue viability and it was found that the presence or absence of peristaltic movements is not directly related to tissue viability. Since so many interferences were found in the results, it is essential that the experimental procedures be standardized, so that the results show less variability and can be compared between different authors

Decline in Public Spending on Biopharmaceutics in Brazil

Abstract Biopharmaceuticals, mainly monoclonal antibodies, and fusion proteins are drugs that have gained notoriety in the treatment of various chronic and inflammatory diseases and have high prices. The study aimed to verify which monoclonal antibodies and fusion proteins were most incorporated into the Unified Health System (SUS), which therapeutic indication most benefited from them and to analyze public spending on these biopharmaceuticals from January 2012 to September 2019. This study performed a qualitative and quantitative analysis of biopharmaceuticals incorporated by SUS. The data were collected on the websites of CONITEC and the Health Price Bank. The results demonstrated that subcutaneous adalimumab was most frequently incorporated, and the most requested therapeutic indication was rheumatoid arthritis. Public spending on biopharmaceuticals exceeded R$ 28 billion (more than US$ 140 billion). However, a downward trend was confirmed (-266.7%) in the period evaluated. Despite the increase in demand and public spending on biologics in general, in Brazil and worldwide, the results of this research show that there was a drop in public spending on the biopharmaceuticals studied in the last seven years.

Biorreactores de un solo uso en la industria biofarmacéutica y su uso en la producción de candidatos vacunales contra SARS- COV-2. Artículo de revisión / Single-use systems bioreactors in the biopharmaceutical industry and its use in SARS-CoV-2 vaccine's candidates production. A review

Los biorreactores de sistemas de un solo uso (SUSs), también conocidos como biorreactores desechables, se han convertido en una parte integral de las instalaciones biotecnológicas de fabricación para bioproductos con un mercado potencial que espera una tasa de crecimiento de casi el 15,5% durante el período pronosticado: 2018 a 2023. Los biorreactores SUSs son más seguros, simples y flexibles al compararlos con sus contrapartes, biorreactores de acero inoxidable, por lo que su uso se está incrementando en la industria biofarmacéutica principalmente en la planificación de vías rápidas de proyectos complejos, incluidos los relacionados con la pandemia de SARS-CoV-2. Así, el uso de SUS se ha convertido en una alternativa eficaz para la producción rápida de candidatos a vacunas. Pero algunas desventajas técnicas y operativas aún obstaculizan su uso en todo el mundo. Esta revisión brinda una visión racional del uso, los tipos, los parámetros operativos y las nuevas aplicaciones de los biorreactores SUSs en la industria biofarmacéutica. Asimismo, también se discuten los parámetros apropiados y las limitaciones de este equipo, enfocándose en su uso para la producción de vacunas contra COVID-19

Single-Use-Systems (SUSs) Bioreactors, also known as disposable bioreactors, have become an integral part of biotechnology manufacturing facilities for bioproducts with a potential market expecting a growth rate of nearly 15.5% over the forecast period: 2018 to 2023. SUSs bioreactors are comparatively safe, simple, and flexible than their stainless-steel bioreactors counterparts thus, their usage is being augmented in the biopharmaceutical industry mainly in planning fast tracks of complex projects, including those related to the SARS-CoV-2 pandemic. Thus, the use of SUSs has become an effective alternative for the rapid production of vaccine candidates. However, some technical and operational disadvantages still hamper their worldwide use. This review gives a rational insight into SUSs bioreactors use, types, operational parameters and new applications in the biopharmaceutical industry. Likewise, the appropriate parameters and limitations of this equipment, focusing on its use for vaccine production against COVID-19 are also discussed

Análisis temático desde el Observatorio Métrico de Coronavirus de las investigaciones publicadas en PubMed / Thematic analysis from the Coronavirus Metric Observatory of the research published in PubMed

La experiencia científica de los últimos meses contra la pandemia de la COVID-19 muestra una celeridad nunca vista, así mismo, es inédita la velocidad en la publicación de los resultados de tales investigaciones. El contexto revela la carrera sostenida que tiene la ciencia contra la expansión de este letal virus. En el presente estudio se documentan evidencias bibliográficas para reconocer a PubMed como uno de los principales recursos de información científica sobre medicina que existen en el mundo. Es una necesidad del gremio científico médico e investigativo en el contexto de la COVID-19 conocer las temáticas que abordan los principales artículos de la base de datos. El objetivo de esta investigación es analizar el comportamiento temático de los artículos publicados por PubMed sobre coronavirus en el primer semestre del año 2020 utilizando como herramienta de análisis al Observatorio Métrico de Coronavirus de la Universidad de Pinar del Río. El interés científico del estudio se concentra en las variables materia, MeSH y palabras clave; las que son analizadas con diferentes técnicas métricas que facilitan la visualización e interpretación de los resultados. Se demostró que PubMed, entre los temas más recurrentes, ha socializado investigaciones en virología, microbiología, farmacéutica, medicina general integral y sus relaciones con la oncología, neurología, pediatría, psicología, psiquiatría, oftalmología, nutrición, telemedicina y dispositivos médicos(AU)

The scientific experience of recent months against the COVID-19 pandemic shows a speed never seen before, likewise, the speed in the publication of the results of such investigations is unprecedented. The context reveals the sustained race in science against the spread of this deadly virus. In this study, bibliographic evidence is documented to recognize PubMed as one of the main sources of scientific information on medicine that exist in the world. In the context of COVID-19, it is a necessity for the scientific, medical and research union to know the issues addressed by the main articles in the database. The objective of this research is to analyze the thematic behavior of the articles published by PubMed on coronavirus in the first half of 2020, using the Coronavirus Metric Observatory of the University of Pinar del Río as an analysis tool. The scientific interest of the study is concentrated in the variables subject, MeSH and keywords; those that are analyzed with different metric techniques that facilitate the visualization and interpretation of the results. It was shown that PubMed, among the most recurrent topics, has socialized research in virology, microbiology, pharmaceuticals, comprehensive general medicine and their relationships with oncology, neurology, pediatrics, psychology, psychiatry, ophthalmology, nutrition, telemedicine and medical devices(AU)

Errores en el registro de datos del sistema intrahospitalario de distribución de medicamentos / Erros in the data registry of the intra-hospital system of drug distribution

INTRODUCCIÓN: los sistemas intrahospitalarios sobre la distribución de medicamentos comprenden múltiples procesos en cadena, con la participación de diferentes personas por lo que es susceptible a la generación de errores. OBJETIVO: el propósito fue conocer la generación de posibles errores durante el proceso de registro de datos en el sistema intrahospitalario de distribución de medicamentos del Instituto Gastroenterológico Boliviano Japonés de Cochabamba. METODOLOGÍA: estudio observacional, descriptivo y transversal; donde se utilizó una lista de cotejos para la revisión del registro realizado en los formularios: kardex, recetario/recibo y hoja de tratamiento en el servicio de internación, así como también el registro de medicamentos dispensados realizado en el servicio de farmacia. RESULTADOS: en el servicio de internación se identificó errores de omisión en el kardex de tratamiento, específicamente en el registro de la forma farmacéutica: comprimidos y frascos. En el servicio de farmacia también se encontró errores de omisión en el registro de las mismas formas farmacéuticas. En los servicios de internación y farmacia, se encontró errores de comisión con el registro de dosis diferente en los formularios recibo recetario y hoja de tratamiento y de medicamento dispensado respectivamente superior al 30% en todos los casos. CONCLUSIONES: los errores identificados en el servicio de internación fueron errores de registro de tipo omisión y comisión. En el servicio de farmacia, los errores encontrados fueron errores de registro de tipo comisión.

Introduction: the intra-hospital drug distribution system, comprise multiple chain processes, with the participation of different people, which is susceptible to the generation of errors. Objective: the purpose was to know the generation of possible errors during the data registration process in the intra-hospital drug distribution system of the Japanese Bolivian Gastroenterological Institute of Cochabamba. Methodology: observational, descriptive and cross-sectional study; where a checklist was used to review the record made in the forms: kardex, recipe book / receipt and treatment sheet in the hospitalization service, as well as the record of dispensed drugs made in the pharmacy service. Results: in the hospitalization service, errors of omission were identified in the treatment kardex, specifically in the registry of the pharmaceutical form: tablets and bottles. In the pharmacy service, errors of omission were also found in the registry of the same pharmaceutical formulations. In the hospitalization and pharmacy services, commission errors were found with the registration of different doses in the forms of prescription, receipt and treatment sheet and of dispensed medication, respectively, higher than 30% in all cases. Conclusions: the errors identified in the hospitalization service were omission and commission type registry errors. In the pharmacy service, the errors found were commission-type registration errors.

Autonomía farmacéutica y biotecnológica frente a emergencias sanitarias / Autonomous pharmaceutical and biotechnological capabilities during sanitary emergencies

La pandemia de COVID 19, ha puesto de presente la necesidad de contar con políticas de autonomía farmacéutica y biotecnológica para cada país. Esta autonomía es necesaria porque en eventos ocasionados por agentes de riesgo biológico, la afectación masiva de la población mundial hace imposible que se cubran las necesidades para todos los países. Muchos medicamentos de interés en salud pública no son producidos por la industria farmacéutica privada dado que los márgenes de ganancia no son importantes para ellos y se encuentran situaciones de desabastecimiento ante brotes de infecciones inusitados.

The COVID 19 pandemic has highlighted the need for pharmaceutical and biotechnology autonomy policies for each country. This autonomy is necessary because in events caused by biological risk agents, the massive involvement of the world population makes it impossible to cover the needs of all countries. Many drugs of public health interest are not produced by the private pharmaceutical industry because the profit margins are not important for them and there are situations of shortages in the event of outbreaks of unusual infections.

Adequação e validação de indicadores de assistência farmacêutica no sistema penitenciário / Adaptation and validation of indicators of pharmaceutical assistance in the penal system / Adecuación y validación de indicadores de asistencia farmacéutica en el sistema penitenciario

O presente estudo tem como objetivo desenvolver indicadores de estrutura, processo e resultados da assistência farmacêutica (AF) penitenciária e validá-los segundo a forma e conteúdo. Para isso, o desenvolvimento metodológico constituiu-se pela elaboração de um painel de indicadores da AF prisional. A elaboração do instrumento de trabalho e a validação de seu conteúdo e forma foram realizados com a utilização da técnica Delfos. Para a inclusão dos indicadores, foi considerada uma concordância entre os especialistas selecionados de 80,0%. O grupo foi composto por dez farmacêuticos que atuam em áreas ligadas à AF. O primeiro instrumento elaborado e submetido a julgamento contemplava 114 indicadores (52 de estrutura, 49 de processo e 13 de resultado). Foram necessárias três rodadas para definição da estrutura, forma e conteúdo dos indicadores, totalizando 50 indicadores validados (28 de estrutura; 16 de processo e 6 de resultado). Os resultados refletem a opinião de especialistas na área e o consenso obtido, validando os indicadores construídos. O uso da técnica Delfos foi pertinente, pois não há dados históricos relacionados ao tema e a opinião de profundos conhecedores da temática proporciona a construção de uma linha de ação coerente e confiável.

This study seeks to develop indicators of structure, process and outcomes of penitentiary pharmaceutical assistance (PA) and validate them according to form and content. This is a methodological development study consisting of the elaboration of a prison PA indicator panel. The elaboration of the instrument and its content and form validation were performed using the Delphi technique. For the inclusion of the indicators, an agreement among the selected experts of 80.0% was considered. The group was composed of 10 pharmacists that worked in areas related to Pharmaceutical Assistance. The first instrument elaborated and subjected to judgment included 114 indicators (52 structure, 49 process indicators and 13 result indicators). It took three rounds to define the structure, shape and content of the indicators, totaling 50 validated indicators (28 structure, 16 process and 6 result indicators). The results reflect the opinion of experts in the field and the consensus obtained, which validates the indicators built. The use of the Delphi technique was pertinent, since there is no historical data related to the theme and the opinion of deep knowledge of the subject provides the construction of a coherent and reliable line of action.

El presente estudio tuvo como objetivo desarrollar indicadores de estructura, proceso y resultados de la asistencia farmacéutica penitenciaria (AF) y validarlos de acuerdo con forma y contenido. Para ello, como metodología se desarrolló un panel de indicadores de AF de la prisión. La elaboración del instrumento de trabajo y la validación de su contenido y forma se llevaron a cabo utilizando la técnica Dephi. Para la inclusión de los indicadores, se consideró un acuerdo del 80,0% entre los expertos seleccionados. El grupo estaba compuesto por 10 farmacéuticos que trabajan en áreas relacionadas con la AF. El primer instrumento desarrollado y sometido a juicio incluyó 114 indicadores (52 de estructura, 49 de proceso y 13 de resultado). Se necesitaron tres rondas para definir la estructura, la forma y el contenido de los indicadores, totalizando 50 indicadores validados (28 de estructura; 16 de proceso y 6 de resultado). Los resultados reflejan la opinión de expertos en el área y el consenso obtenido, que valida los indicadores construidos. El uso de la técnica Dephi fue pertinente, ya que no hay datos históricos relacionados con el tema y la opinión profundizada de expertos sobre el tema proporciona elaborar una línea de acción coherente y confiable.

Aplicación del Análisis de Componentes Principales en el proceso de purificación de un biofármaco / Application of Principal Component Analysis in the purification process of a biopharmaceutical

En este trabajo se presenta la aplicación del Análisis de Componentes Principales, mediante el programa THE UNSCRAMBLER versión 8.0, a los datos registrados en un período de 2 años en la etapa de purificación de una planta de producción de Eritropoyetina Humana Recombinante que está basada en varios pasos cromatográficos, de forma similar a los procesos de purificación de proteínas recombinantes que se utilizan como vacunas preventivas o terapéuticas. Se logró reducir dimensionalidad al obtenerse dos componentes principales que explican el 81 por ciento de la varianza de 18 variables originales relacionadas con cuatro pasos cromatográficos. Como resultado se llegó a definir cuáles son las variables que mayor aporte tienen a la variabilidad del proceso en la etapa de purificación, permitiendo extraer información útil para lograr un mayor entendimiento del proceso y enriquecer las estrategias de control en la planta. Dichos resultados corroboraron experiencias prácticas de especialistas de la planta y permitieron dar recomendaciones a considerar en el plan de verificación continuada del proceso como proponer cinco variables como controles de proceso y tener en cuenta que el rendimiento del segundo paso cromatográfico es el más influyente de los rendimientos considerados en la variabilidad(AU)

This paper presents the application of the Principal Component Analysis, using the program THE UNSCRAMBLER version 8.0, to the data recorded during two years in the purification stage of a Recombinant Human Erythropoietin plant that is based on several chromatographic steps, similar to the purification process of recombinant proteins that are used as preventive or therapeutic vaccines. Dimensionality was reduced by obtaining two main components that explain 81 percent of the variance of 18 original variables related to four chromatographic steps. As a result, it was possible to define which variables have the greatest contribution to the variability of the process in the purification stage, allowing to extract useful information to achieve a greater understanding of the process and enrich the control strategies in the plant. These results corroborated practical experiences of plant specialists and allowed for recommendations to be considered in the continuous verification plan of the process, such as proposing three variables as process controls and taking into account that the performance of the second step is the most influential of the performances considered in the variability(AU)

Visión de la innovación en un centro cubano de la biotecnología aplicada a la salud / Vision of innovation in a Cuban center of biotechnology applied to health

Introducción: La evaluación de los factores claves de éxito de la innovación en la industria biotecnológica aplicada a la salud constituye un problema de investigación. Objetivo: Evaluar la innovación en un centro cubano de la biotecnología aplicada a la salud. Métodos: Se aplicó en dos momentos la encuesta de innovación en el Centro de Inmunología Molecular. Los resultados se procesaron con el diagrama de caja, la estadística básica y el análisis de la correlación. Se analizaron artículos científicos que muestran los resultados de la innovación en el centro. Resultados: La encuesta se aplicó en el 2015 y 2018 a 33 miembros del consejo de dirección y a especialistas, identificándose como estrategias genéricas las de innovación, calidad y liderazgo y como objetivos de innovación los de calidad y el mercado. Las fuentes de innovación más importantes se refieren a las actividades de investigación y desarrollo, la producción, la alta dirección y los centros de investigaciones. Los factores que limitan están relacionados con el período largo de rentabilidad de la innovación, el financiamiento y la adquisición de los insumos. Conclusiones: La evaluación de la innovación en el centro de biotecnología corroboró la significación que tiene para la empresa la estrategia de innovación como factor clave, que lo ubica en una posición de excelencia en la industria biofarmacéutica cubana e internacional(AU)

Introduction: The assessment of the key success factors of innovation in the biotechnology industry applied to health constitutes a research problem. Objective: To assess innovation process in a Cuban center of biotechnology applied to health. Methods: It was applied in two moments the survey of innovation in the Molecular Immunology Center. The results were processed by the box plot, basic statistics and analysis of the correlation. Scientific articles that show the results of innovation in the Center were analyzed. Results: The survey was applied in 2015 and 2018 to 33 members of the board of directors and to specialists, and being identified innovation, quality and leadership as generic strategies, and quality and the market as objectives of innovation. The most important sources of innovation referred to the research and development activities, production, top management and research centers. The limiting factors are related to the long term return of innovation, financing, and the acquisition of supplies. Conclusions: The assessment of innovation in the Biotechnology Center corroborated the significance of the innovation strategy for the company as a key factor, which places it in a position of excellence in the Cuban and international biopharmaceutical industry(AU)

Estudio de bioequivalencia in vitro de comprimidos de liberación inmediata de metformina de 850 mg comercializados en Bolivia / In vitro bioequivalence study of immediate release tablets of 850 mg of metformin marketed in Bolivia

INTRODUCCIÓN: los estudios de bioequivalencia demuestran la equivalencia en la calidad biofarmacéutica entre el producto farmacéutico multifuente y el medicamento de referencia, permitiendo el establecimiento de puentes entre las pruebas preclínicas y los ensayos clínicos asociados con el medicamento de referencia. La Metformina clorhidrato es el fármaco de primera elección para el tratamiento de la diabetes mellitus II y pertenece a la clase 3 del sistema de clasificación biofarmacéutica. OBJETIVO: establecer mediante pruebas de disolución in vitro, si 4 productos farmacéuticos multifuentes de liberación inmediata, de administración peroral, con Metformina clorhidrato, comercializados en Bolivia son bioequivalentes en relación con el producto de referencia, a través de un diseño experimental, con significancia estadística. MÉTODO: Se elaboraron perfiles de disolución de cada producto, tomando en cuenta las condiciones del método del ensayo de disolución establecido en la monografía Metformina, tabletas de la USP 39, considerando seis tiempos de muestreo. Se realizó el análisis cinético de los datos de porcentaje disuelto acumulado de los perfiles de disolución versus el tiempo. Se empleó el método de modelo independiente para comparar los perfiles de disolución de los productos a través del cálculo de los factores de diferencia (f1) y de similitud (f2) recomendados para estudios de bioexención por la Organización Mundial de la Salud. RESULTADOS: todos los productos tomados en cuenta en la investigación cumplieron satisfactoriamente los análisis de Control de Calidad. Los resultados del estudio de Bioequivalencia mostraron que existen diferencias estadísticamente significativas entre los productos del estudio. CONCLUSIÓN: en este estudio no se demostró la Bioequivalencia in vitro de los productos B, C, D y E con relación al producto de referencia A, con base en pruebas de disolución in vitro.

INTRODUCTION: bioequivalence studies demonstrate the equivalence in biopharmaceutical quality between the multi-source pharmaceutical product and the reference medicine, allowing the establishment of bridges between preclinical tests and clinical trials associated with the reference medicine. Metformin hydrochloride is the drug of first choice for the diabetes mellitus II treatment and belongs to class 3 of the Biopharmaceutical Classification System. OBJECTIVE: establish by in vitro dissolution tests, whether 4 multisource pharmaceutical products of immediate release and peroral administration, with Metformin hydrochloride, marketed in Bolivia are bioequivalent in relation to the reference product, through an experimental design, with statistical significance. METHOD: dissolution profiles were prepared for each product, taking into account the conditions of the dissolution test method established in the Metformin, tablets monograph of USP 39, considering six sampling times. The kinetic analysis of the accumulated dissolved percentage data of the dissolution profiles versus time was performed. The independent model method was used to compare the dissolution profiles of the products by calculating the difference factor (f1) and similarity factor (f2) recommended for Biowaiver studies, by the World Health Organization. RESULTS: All the products taken into account in the investigation, satisfactorily fulfilled the Quality Control analysis. The results of the Bioequivalence study showed that there are statistically significant differences between the products of the study. CONCLUSION: In this study the in vitro bioequivalence of the products B, C, D and E in relation to the reference product A was not demonstrated, based on in vitro dissolution tests.

Equilibrium solubility study to determine fexofenadine hydrochloride BCS class and challenges in establishing conditions for dissolution profiles applied to suspension

The aim of this work was to perform solubility studies for fexofenadine hydrochloride and establish dissolution conditions for this drug in oral suspension dosage form. The solubility study was executed through the shake-flask method, below 37 ºC±1 ºC, at 100 rpm stirring for 12 h in three buffer solutions: hydrochloric acid pH 2.0, acetate pH 4.5 and phosphate pH 6.8. The dissolution test was developed in vessels containing 900 mL of the same buffer, employing the paddle apparatus in speed of 25 and 50 rpm, below 37 ºC±0.5 ºC. The drug was classified as low solubility according to the Biopharmaceutics Classification System, since the dose/solubility ratio was higher than 250 mL in all media tested (326.55 mL in buffer pH 2.0; 2,456.33 mL in buffer pH 4.5 and 1,021.16 mL in buffer pH 6.8). The dissolution test showed that a release of 85% in 30 min could be established. The rotation speed of 25 rpm, media volume of 900 mL and insertion of the samples through weighted syringes are adequate. The buffered media pH 2.0 could be chosen as dissolution media.

Studying the technology for obtaining pharmaceutical substances and determination of biologically active substances in them

In searching for alternatives to traditional chemical medicines, including feed antibiotics, scientists around the world are developing a new generation of medicines, phytobiotics. This work was aimed at studying the phytobiotics (pharmaceutical substances) production technology using the method of low-temperature vacuum water-ethanol extraction of Siberian medicinal plants, followed by low-temperature vacuum drying and determination of the main biologically active substances that had the required pharmacological effect on the organisms of farm animals and poultry. The objects of the study in this work were Siberian medicinal plants and ready phytobiotics (pharmaceutical substances). The article describes the technological conditions for obtaining pharmaceutical substances and their properties concerning the content of biologically active substances. It has been found that for obtaining pharmaceutical substances, extraction should be performed in three stages: two water extractions and ethanol- water extraction. The article provides a list of medicinal plants and the amounts of biologically active substances that ensure certain pharmacological effects on the set of economically useful qualities in farm animals and poultry and contained in phytobiotics (pharmaceutical substances) based on extracts from medicinal plants.

Research and development thought on biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.

Applicability analysis and evaluation of aglycones in single-pass intestinal perfusion technique based on PBPK model / 中国中药杂志

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.

Research on attributes of biopharmaceutics classification system for Chinese materia medica of baicalein in Gegen Qinlian Decoction environment / 中国中药杂志

For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).