Chromatographic study of sitagliptin and ertugliflozin under quality-by-design paradigm

Abstract The present study entails the systematic development and validation of a stability-indicating RP-HPLC method for the analysis of sitagliptin and ertugliflozin in a fixed-dose combination. Analytical quality by design (AQbD) concepts were used to define critical method variables, employing Pareto risk assessment and a Placket-Burman screening design, preceded by a Box-Behnken design with response surface analysis to optimise critical method parameters such as % acetonitrile (X1), buffer pH (X2) and column oven temperature (X3). Multiple response optimisation (Derringer's desirability) of variables was accomplished by studying critical analytical attributes, such as resolution, retention time and theoretical plates. The title analytes were separated effectively on a PRONTOSIL C18 column at 37 °C using a mobile phase of acetonitrile:acetate buffer, pH 4.4 (36:64 percent v/v), pumped at a flow rate of 1 mL/min, and UV detection at 225 nm. Linearity was observed over a concentration range of 25-150 µg/mL and 3.75-22.5 µg/mL at retention times of 2.82 and 3.92 min for sitagliptin and ertugliflozin, respectively. The method obeyed all validation parameters of the ICH Q2(R1) guidelines. The proposed robust method allows the study of the selected drugs in pharmaceutical dosage forms as well as in drug stability studies under various stress conditions.

Separation and determination of D-malic acid enantiomer by reversed-phase liquid chromatography after derivatization with (R)-1-(1-naphthyl) ethylamine

Abstract L-Malic acid is the Active Pharmaceutical Ingredient of the latest generation of compound electrolyte injection (STEROFUNDIN ISO, Germany) and plays a very important role in the rescue of critically ill patients. The optical purity of L-malic acid is a Critical Quality Attributes. A new reversed-phase high performance liquid chromatography (RP-HPLC) method for pre-column derivatization of D-malic acid enantiomer impurity in L-malic acid bulk drug was established. The derivatization reaction was carried out using (R)-1-(1-naphthyl)ethylamine ((R)-NEA) as a chiral derivatization reagent. The Kromasil C18 column was used with a detection wavelength of 225 nm, a flow rate of 1.0 mL·min-1, and a column temperature of 30 °C. The mobile phase was acetonitrile-0.01 mol·L-1 potassium dihydrogen phosphate solution (containing 20 mmol·L-1 sodium heptanesulfonate, adjusted to pH 2.80 with phosphoric acid) (at a ratio of 45:55) and the resolution of D-malic acid and L-malic acid derivatization products reached 1.7. The proposed method possesses the advantages of simple operation, mild conditions, stable derivatization products and low cost. Also it gave better separation and was more accurate than previous methods

Extração de recomendações farmacológicas para subsidiar o processo de adaptação de guias de prática clínica utilizados no tratamento da fibrilação atrial não valvar - uma revisão sistemática de guias de prática clínica / Extraction of pharmacological recommendations to support the process of adaptation of clinical practice guides used in the treatment of non-valvular atrial fibrillation a systematic review of clinical practice guidelines

A fibrilação atrial (FA) não valvar é a arritmia cardíaca mais comum em adultos, principalmente na população idosa. Para o tratamento da FA, recomenda-se a utilização de guias de prática clínica (GPCs), que são documentos que apresentam as melhores e mais atualizadas evidências para o tratamento dos pacientes acometidos por essa arritmia. Todavia, o processo de desenvolvimento dos GPCs requer recursos humanos, financeiros e tempo. Assim, a adaptação dos referidos documentos é uma opção para reduzir a duplicação de esforços e possibilitar sua adequação para uso local. O objetivo deste trabalho foi elaborar uma matriz de recomendações farmacológicas para subsidiar o processo de adaptação de GPCs utilizados no tratamento da fibrilação atrial não valvar. Para tanto, aplicou-se o método ADAPTE: revisão sistematizada de GPCs, avaliação e seleção dos GPCs de qualidade e elaboração da matriz. Foram considerados elegíveis 26 GPCs com recomendações farmacológicas para assistência primária da fibrilação atrial não valvar em adultos, publicados em inglês, espanhol ou português no período de abril de 2014 a abril de 2019 e indexados às bases de referência: MEDLINE, Embase, Cochrane Library e em 12 bases de dados específicas. A qualidade dos GPCs, foi avaliada pela aplicação do instrumento Appraisal of Guidelines for Research & Evaluarion II (AGREE II), sendo considerados de alta qualidade aqueles que apresentaram nota igual ou superior a 60 % no domínio Rigor de desenvolvimento. Todas as etapas foram realizadas por, pelo menos, 2 avaliadores e em caso de discrepância, um terceiro avaliador participou do processo. Dos 26 GPCs avaliados apenas 7 (26,9%) foram considerados de alta qualidade. A maioria dos GPCs utiliza o escore CHA2DS2-VASc, que indica a profilaxia tromboembólica em pacientes com FA não valvar a partir da pontuação 1 (fator de risco não sexual) e sugere a anticoagulação com anticoagulantes de ação direta. Houve pouca ênfase à complexidade da profilaxia de eventos tromboembólicos em idosos. Esta matriz visa contribuir para que sejam realizadas discussões e adaptações de GPCs destinado ao tratamento da FA não valvar com ênfase nas demandas e necessidades locais

Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia in adults, especially in the elderly population. For the treatment of AF, the use of clinical practice guidelines (CPGs) is recommended, which are documents that present the best and most up-to-date evidence for the treatment of patients who are affected by this arrhythmia. However, the CPGs development process requires human, financial and time resources. However, the adaptation of documents is an option to reduce the duplication of efforts and make it possible to adapt them for any local use. The objective of this work was to elaborate a matrix of pharmacological treatment to support the process of adaptation of CPGs used in the treatment of non-valvular atrial fibrillation. Therefore, the ADAPTE method was applied: systematic review of CPGs, evaluation and selection of quality CPGs and matrix definition. Twenty-six CPGs were considered eligible with pharmacological recommendations for primary care of non-valvular atrial fibrillation valid in adults, published in English, Spanish or Portuguese from April 2014 to April 2019 and indexed to the following reference databases: MEDLINE, Embase, Cochrane Library and in 12 specific databases. The quality of the CPGs was assessed by applying the Assessment of Guidelines for Research and Assessment II (AGREE II) instrument, being considered of high those who had a grade equal to or greater than 60% in the domain Rigour of development. All steps were performed by a least 2 evaluators and in case of discrepancy, a third evaluator participated in the process. Of the 26 CPGs evaluated, only 7 (26.9%) were considered to be of high quality. Most CPGs use the CHA2DS2-VASc score, which indicates thromboembolic prophylaxis in patients with non-valvular AF from score 1 (non-sexual risk factor), and suggest anticoagulation with direct-acting anticoagulants. There was little emphasis on the complexity of prophylaxis for thromboembolic events in the elderly. This matrix aims to contribute to discussion and adaptations of CPGs for the treatment of non-valvar AF with the emphasis on local demands and needs

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Definición y estabilización de los procesos II. Procesos clínicos en un Servicio de Urología / Definition and stabilization of processes II. Management processes and support in a Urology Department

Los nuevos modelos de gestión clínica persiguen una práctica clínica basada en la calidad, la eficacia y la eficiencia evitando la variabilidad y la improvisación. En este trabajo, hemos desarrollado uno de los procesos clínicos más frecuentes en nuestra especialidad: el basado en el GRD 311 o procedimentos transuretrales sin complicaciones. A lo largo del mismo describiremos sus componentes: el formulario de estabilización, la trayectoría clínica, el cálculo de costes, y finalmente el diagrama de flujo del proceso

New models in clinical management seek a clinical practice based on quality, efficacy and efficiency, avoiding variability and improvisation. In this paper we have developed one of the most frequent clinical processes in our speciality, the process based on DRG 311 or transurethral procedures without complications. Along it we will describe its components: Stabilization form, clinical trajectory, cost calculation, and finally the process flowchart

Curso de gestión de la calidad para laboratorios / Course of management of the quality for laboratories Module 6. Equipment and materials

Medicina & Laboratorio ha recibido los derechos de publicación de la Organización Panamericana de la Salud, para reproducir en su totalidad el ®Curso de Gestión de Calidad para laboratorios¼, una excelente herramienta para el mejoramiento continuo del desempeño de los laboratorios. La vigilancia de la salud tanto individual como de la población general, el desarrollo de un número creciente de técnicas de laboratorio y la mejora continua de los métodos diagnósticos requieren la adopción de herramientas de gestión para su óptima implementación en los sistemas y laboratorios de salud. Por estas razones, entre otras, el concepto universal de calidad y el estudio de sus procesos se han extendido de la industria de la manufactura a las ciencias médicas. No sólo lo anteriormente mencionado, sino también el buen servicio y la satisfacción del cliente -o de los usuarios- son objetivos primordiales para los hospitales y laboratorios que tratan de establecer un sistema de gestión de la calidad que se adapte tanto a las necesidades operativas y fiduciarias de su organización, como a los requisitos prácticos de los usuarios: pacientes, médicos, epidemiólogos, autoridades sanitarias y comunidad entre otros.El objetivo de este curso es brindar capacitación en los principios básicos necesarios para la gestión de la calidad en los laboratorios. El contenido de los módulos incluye una información apropiada que, junto a la terminología descrita, permite la familiarización del participante con los conceptos básicos sobre las principales áreas de un sistema de gestión de la calidad.

Large multispecialty group practices and quality improvement: what is needed to transform care?

The objective of this study was to use successful quality improvement initiatives in large multispecialty medical groups to identify the organizational factors that were the most important to improvement. The study analyzed the most successful quality improvement initiatives from those submitted by the 24 members of the Council of Accountable Physician Practices. Twelve initiatives from 8 groups were selected that met the study criteria for large improvement for large numbers of patients. An independent group used these initiatives to identify potentially important factors and then asked key local leaders to rate the importance of these factors on a scale of 1 to 4, importance rating (1-4 scale) for each of 18 identified factors. Eighteen factors were identified and 5 stood out as ranked a 4 (Very Important) for at least 80% of the initiatives: Communication, Use of Evidence-Based Medicine, Leadership, Measurement, and Reporting. Another 7 of the 18 factors were ranked a 4 for more than 50% of the initiatives. All the factors are related to the 6 challenges in the Institute of Medicine report. It was concluded that any organization striving to greatly improve the quality of its healthcare delivery should consider these factors when planning improvement initiatives.

Gestión por procesos asistenciales integrados en el sistema sanitario público de Andalucía

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Un modelo de gestión de la calidad total para la enfermería hospitalaria / A model of total quality management for the hospital nursing

Introducción: El modelo Europeo para la Gestión de la calidad Total (EFQM) se sintetiza de la siguiente manera: La satisfacción de los clientes y empleados, se consiguen mediante un liderazgo que impulse la política y estrategia de la organización a través de una adecuada utilización de los recursos con una perfecta gestión de los procesos más importantes de la organización con objeto de conseguir unos resultados excelentes. Existen algunas experiencias aisladas en Europa y algunos proyectos en marcha en España que intenta adaptar el modelo EFQM para instituciones sanitarias. Este modelo, al igual que puede ser aplicable al contexto general de las actividades que se llevan a cabo en un hospital, también sería posible circunscribirlo al área de los cuidados de enfermería. Es precisamente ésta aplicación la que hemos llevado a cabo. Objetivo: Evaluar mediante un modelo de excelencia de gestión de calidad total la enfermería hospitalaria. Material y Métodos: Se presenta un estudio basando en técnicas de investigación cualitativas (brainstorming, Técnica de grupo nominal-TGN), en el que diferentes enfermeros expertos (clínicos, gestores y docentes) y pacientes lograron consenso sobre los aspectos, contenidos, instrumentos y métodos, que basados en los criterios del modelo EFQM, sirvan para medir la calidad de los cuidados de enfermería en los hospitales. Completado el modelo, que consta de más de 500 áreas o criterios de evaluación, se aplicó en el área materno infantil de 3 hospitales del Servicio Andaluz de Salud. Resultados: Se contrastan los resultados obtenidos en los tres centros y las dificultades que ha presentado su aplicación. De los resultados se desprende que en todos los criterios y en todos los hospitales existen innumerables aéreas que mejorar y que las puntuaciones obtenidas (373,4, 174,3 y 193,1 sobre 1.000) distan mucho de las obtenidas por organizaciones excelentes. Conclusión: El modelo nos muestra una herramienta útil y exhaustiva, que puede ser utilizada para la detección y priorización de oportunidades de mejora, sobre las cuales podemos intervenir para alcanzar mejoras en las distintas áreas abordadas (AU)

Calidad percibida. una revolución silenciosa / Perceived quality: a silent revolution

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Quality, CQI, and reengineering in health services organizations.

Quality in health care is defined with a focus on satisfying customer needs. The contemporary management philosophies of continuous quality improvement (CQI) and reengineering are defined; attributes and applications of each are described. Criticism of reengineering appearing in the literature is presented. It is likely that CQI will remain a predominate management philosophy in health services, while reengineering may not endure in its form of radical change.

Gestión de la Calidad total: la Solución Natural en la gestión de GASNALSA / TQM: the natural solution in Gasnalsa's management

En el artículo se describe la estrategia que ha seguido una PYME del sector del gas: Gasnalsa, desde 1992 para convertirse en uno de los líderes en gestión y excelencia empresarial, a través de la implantación de un sistema de gestión de calidad total al que se denomina "la solución natural". Mediante este sistema se pretende conseguir la satisfaccción de todos los grupos de interés, una relación transparente con los clientes, potenciando sus características diferenciadoras, procurando que la excelencia se convierta en un hábito en la organización, para que cada uno de los trabajadores dé lo mejor de sí mismo de forma individual y se integre en el grupo como un todo (AU)

Building a framework for multiple improvement initiatives.

BACKGROUND: As health care organizations struggle to compete and even survive in today's turbulent marketplace, they often juggle a variety of initiatives addressing cost reduction, quality improvement, critical pathways, accreditation, clinical guidelines, strategic planning, and organizational development-each with its own priorities, advocates, methods, and language. EXAMPLE: One large health care system that had adopted continuous quality improvement (CQI) as a major strategy then responded to significant cost pressures with additional initiatives in reengineering, cost reduction, and physician guidelines, with varying connections to the quality language, principles, and methods. The senior leadership committee for the quality initiative undertook the development of a framework to explain the connections among the diverse projects and approaches-a framework still in use after two years. SUMMARY AND CONCLUSION: In this period of enormous change, health care leaders must quickly and effectively mobilize all available resources to optimize organizational effectiveness. Too often, management's response patterns have overemphasized a "splitting" tactic, managing multiple distinct initiatives. The creation of integrated delivery systems, mergers, acquisitions, and alliance exacerbates this problem, as the number of initiatives multiplies in the new organizations. Development and application of an integrating management framework will accelerate the pace of organizational improvement by increasing shared understanding of the current desired states of the organization; linking strategic, cultural, and method needs and behaviors; aligning various management initiatives in relation to organizational goals and one another; increasing the fit of management methods with specific situations; and providing a unifying perspective and language for organizational members to act and learn collaboratively.

The Highmark Pegasus Project report: characteristics of highly successful health plans.

The Highmark Blue Cross/Blue Shield Pegasus Project was created in the fall of 1996 to benchmark best practices at health plans around the United States through extensive interviews, literature searches, and other measures. Characteristics of highly successful health plans across a number of major categories are summarized in the final recommendations presented by this report.