Semisolid formulations based on solid-in-oil-in-water systems containing proteins

Abstract In recent years, improvements have been made, through biotechnological processes, in the production and development of peptides capable of increasing collagen and elastin synthesis for anti-aging skin care. However, proteins have many limitations due to their structural, chemical and physical fragility to external aggressions, which may cause conformational changes, leading to loss of biological activity. Therefore, it is important to create delivery systems that protect these biomolecules from damage, allowing them to reach their target. This work aimed to develop a system able to carry bovine serum albumin (BSA), used as a model of a protein, and to incorporate this system in a semisolid formulation suitable for skin application. A microemulgel based on a solid-in-oil-in-water (S/O/W) microemulsion was prepared. Firstly, the association efficiency (AE) of lyophilized BSA-sucrose ester complex and the size of S/O nanodispersion were assessed; then, the characterization and stability evaluation of the final semisolid formulation through evaluation of pH, texture and rheological behavior were performed. The average value of AE was 54.74% ± 2.17. It was possible to develop an S/O/W microemulsion, which allowed the subsequent development of an S/O/W microemulgel that assured suitable pH, texture and rheological characteristics for skin application.

Uso de indicadores na avaliação do serviço de educação permanente: reflexão dos pilares da qualidade / Uso de indicadores en la evaluación del servicio de educación permanente: reflexión de los pilares de la calidad / Use of indicators in the evaluation of the permanent education service: reflection of the quality pillars

Objetivo refletir sobre o uso de indicadores na avaliação da qualidade do serviço de educação permanente. Método estudo descritivo, tipo análise reflexiva da literatura, à luz dos pilares da qualidade. Resultados a avaliação da qualidade do serviço de educação permanente remete ao monitoramento dos indicadores associados à frequência dos profissionais nas atividades propostas, abandono na sequência dos treinamentos e satisfação com as atividades. Outros indicadores são relacionados ao próprio serviço de educação permanente, mediante o monitoramento da taxa de cancelamento das ações, tempo médio de capacitações e o valor investido no planejamento das ações. Dessa forma, a avaliação dos indicadores com base nos pilares da qualidade de eficácia, efetividade, eficiência, aceitabilidade, legitimidade e equidade pode auxiliar no planejamento e na análise dos treinamentos ofertados. Conclusão o uso de indicadores na educação permanente favorece a análise retrospectiva e prospectiva das atividades por meio dos próprios profissionais e do serviço de educação permanente.

Objetivo reflexionar sobre el uso de indicadores en la evaluación de la calidad del servicio de educación permanente. Método estudio descriptivo, análisis reflexivo de la literatura, a la luz de los pilares de la calidad. Resultados la evaluación de la calidad del servicio de educación permanente se refiere al monitoreo de los indicadores asociados a la frecuentación de los profesionales en las actividades propuestas, el abandono en la secuencia de la formación y la satisfacción con las actividades. Otros indicadores se relacionan con el propio servicio de educación permanente, a través del monitoreo de la tasa de cancelación de acciones, el tiempo promedio de capacitación y el valor invertido en la planificación de acciones. Así pues, la evaluación de los indicadores basados en los pilares de la calidad de la eficacia, efectividad, eficiencia, aceptabilidad, legitimidad y equidad puede auxiliar en la planificación y el análisis de la formación ofrecida. Conclusión la utilización de indicadores en la educación permanente favorece el análisis retrospectivo y prospectivo de las actividades a través de los propios profesionales y del servicio de educación permanente.

Objective to reflect on the use of indicators in the evaluation of the quality of the continuing education service. Method descriptive study, reflective analysis of literature, in the light of the quality pillars. Results the evaluation of the quality of the permanent education service refers to the monitoring of indicators associated with the attendance of professionals in the proposed activities, abandonment in following training and satisfaction with activities. Other indicators are related to the permanent education service itself, through the monitoring of the cancellation rate of actions, average training time and the value invested in the planning of actions. Thus, the evaluation of the indicators based on the pillars of quality of efficacy, effectiveness, efficiency, acceptability, legitimacy and equity is able to assist in the planning and analysis of the training offered. Conclusion the use of indicators in permanent education favors the retrospective and prospective analysis of the activities by the professionals themselves and by the permanent education service.

Characterization and stability studies of emulsion systems containing pumice

Emulsions are the most common form of skin care products. However, these systems may exhibit some instability. Therefore, when developing emulsions for topical application it is interesting to verify whether they have suitable physical and mechanical characteristics and further assess their stability. The aim of this work was to study the stability of emulsion systems, which varied in the proportion of the emulsifying agent cetearyl alcohol (and) sodium lauryl sulfate (and) sodium cetearyl sulfate (LSX), the nature of the oily phase (decyl oleate, cyclomethicone or dimethicone) and the presence or absence of pumice (5% w/w). While maintaining the samples at room temperature, rheology studies, texture analysis and microscopic observation of formulations with and without pumice were performed. Samples were also submitted to an accelerated stability study by centrifugation and to a thermal stress test. Through the testing, it was found that the amount of emulsifying agent affects the consistency and textural properties such as firmness and adhesiveness. So, formulations containing LSX (5% w/w) and decyl oleate or dimethicone as oily phase had a better consistency and remained stable with time, so exhibited the best features to be used for skin care products.

Emulsões são a forma de apresentação mais comum dos produtos para aplicação na pele. No entanto estes sistemas podem exibir alguma instabilidade. Por esta razão, quando do desenvolvimento de emulsões para aplicação tópica é importante verificar se estas apresentam propriedades físicas ou mecânicas adequadas e avaliar a sua estabilidade. O objetivo deste trabalho consistiu no estudo da estabilidade de emulsões, cujas variações entre elas foi a proporção de agente emulsificante álcool estearílico (mais) laurilsulfato de sódio (mais) estearilsulfato de sódio (LSX), a natureza da fase oleosa (decil oleato, ciclometicona ou dimeticona) e a presença ou ausência de pedra-pomes (5% m/m). Mantendo as amostras à mesma temperatura, realizaram-se o estudo da reologia, a análise de textura e observação microscópica das formulações com e sem pedra-pomes. Amostras foram, também, submetidas a estudo de estabilidade acelerada por centrifugação e a ensaio de estresse térmico. Através dos testes realizados, constatou-se que a quantidade de agente emulsificante influencia a consistência e as propriedades de textura, como a firmeza e a adesividade. As formulações contendo LSX (5% m/m) e decil oleato ou dimeticona como fase oleosa exibiram melhores caraterísticas como produtos para aplicação na pele, uma vez que estas formulações apresentaram menor firmeza e consistência e permaneceram estáveis com o tempo.

Use of solid dispersions to increase stability of dithranol in topical formulations

The present study was planned to improve the stability of dithranol using solid dispersions (SD). Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio) as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature), high temperature exposition (37 °C) (protected from light) and protected from light (room temperature). Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.

Este trabalho teve como objetivo aumentar a estabalidade do ditranol através da preparação de dispersões sólidas (DS). Prepararam-se duas DS diferentes em proporção de 1:9 de ditranol/excipiente: em uma das DS utilizou-se beenato de glicerila como excipiente e na outra se utilizou mistura de óleo de argan com ácido esteárico (razão 1:8). Posteriormente, efetuou-se a incorporação de ditranol puro e das DS contendo este fármaco num creme hidrófilo ou óleo-água (O/A) e em pomada hidrófoba, na proporção 1:10 (fármaco ou respetivas DS/base dermatológica). As propriedades físicas e mecânicas das formulações semissólidas incorporando fármaco ou as respetivas DS previamente desenvolvidas, foram avaliadas através da análise do comportamento reológico e das propriedades de textura. Para avaliar a estabilidade, os parâmetros do espaço de cor L*a*b* das DS e das formulações semissólidas e o pH das preparações hidrófilas foram determinados em períodos de tempo definidos, durante um mês para cada amostra armazenada sob diferentes condições, especificamente, exposição à luz (à temperatura ambiente), protegidas da luz à temperatura elevada (37 °C) e protegidas da luz (temperatura ambiente). Embora tenham apresentado valores de firmeza e de adesividade mais elevados, as pomadas hidrófobas apresentaram melhores características reológicas do que os cremes óleo-água. Além disso, as pomadas hidrófobas também apresentaram melhor estabilidade, com pequenas alterações nos parâmetros do espaço de cor L*a*b*. Os resultados deste trabalho permitiram concluir que as DS desenvolvidas contribuíram para o aumento da estabilidade do ditranol.

Prolonged-release lipid microparticles prepared with decyl oleate and hydrogenated castor oil of ibuprofen.

Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles of ibuprofen with decyl oleate and hydrogenated castor oil were prepared. This formulation was intended to improve the content of ibuprofen in preparation and to sustain the release of this drug. Lipid microparticles were submitted to determination of ibuprofen content using UV-VIS spectrophotometry and, gelatin capsules filled with lipid microparticles and tablets prepared with these microparticles were submitted to dissolution tests in order to study the influence of the prepared system in the release profiles of ibuprofen. The improvement of the content of ibuprofen and prolonged release of this drug was achieved with the lipid microparticles prepared with this mixture of excipients.

Prolonged-release solid dispersions of ibuprofen.

Ibuprofen (IB) is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory chronic diseases. This drug presents, in the pure state, poor physical and mechanical characteristics and their use in solid dosage forms needs the addition of excipients which improve these properties. The selection of the best excipients and the suitable pharmaceutical dosage form to carry ibuprofen are very important for the industrial success of this drug. Thus, in this work, solid dispersions of ibuprofen in cethyl alcohol (SD CA), stearic acid (SD SA) and hydrogenated castor oil (SD HCO) were prepared in order to improve physical and mechanical characteristics of this drug. Physical mixtures with the same composition of solid dispersions were also prepared. Solid dispersions of ibuprofen with stearic acid and hydrogenated castor oil showed better flow characteristics than pure ibuprofen and the respective physical mixtures. Gelatin capsules filled with solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged-release of ibuprofen was achieved with the solid dispersions prepared with the different types of excipients.

Temperature and pH stimuli-responsive polymers and their applications in controlled and selfregulated drug delivery.

Controlled drug delivery is useful because it allows to obtain better drug product effectiveness, reliability and safety. Interest in stimuli-responsive polymers is steadily gaining increasing momentum especially in the fields of controlled and self-regulated drug delivery. Stimuliresponsive or “smart“ polymers are macromolecules that display a significant physiochemical change in response to small changes in their environment such as temperature, pH, light, magnetic field, ionic factors, etc. The changes are reversible, and therefore, the smart polymers are capable of returning to its initial state as soon as the trigger is removed. They have become one important class of polymers and their applications have been increasing significantly in the last three decades. Smart polymers have very promising applications in the biomedical field as delivery systems of therapeutic agents, tissue engineering scaffolds, cell culture supports, bioseparation devices, etc. The versatility and untapped potential of smart polymeric materials makes them one of the most promising interfaces of chemistry and biology.

Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.

O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões sólidas de ibuprofeno com cada um dos seguintes excipientes: álcool cetílico, ácido esteárico e óleo de rícino hidrogenado. Estas formulações tinham por finalidade melhorar as características físicas e mecânicas e prolongar a liberação deste fármaco. Foram, também, preparadas misturas físicas do ibuprofeno com os mesmos excipientes e nas mesmas proporções. As dispersões sólidas de ibuprofeno/ácido esteárico e as dispersões sólidas de ibuprofeno/óleo de rícino hidrogenado foram aquelas que apresentaram melhores características de escoamento comparativamente com o ibuprofeno puro. Por outro lado, foram preparadas cápsulas de gelatina com as diferentes micropartículas lipídicas e dispersões sólidas e submetidas a ensaios de dissolução com o objetivo de estudar a influência dos sistemas preparados nos perfis de liberação do ibuprofeno. A liberação prolongada do ibuprofeno foi conseguida nas diferentes micropartículas lipídicas e dispersões sólidas preparadas com os diferentes excipientes.

Drugs obtained by biotechnology processing / Drogas obtidas pelo processamento biotecnológico

In recent years, the number of drugs of biotechnological origin available for many different diseases has increased exponentially, including different types of cancer, diabetes mellitus, infectious diseases (e.g. AIDS Virus / HIV) as well as cardiovascular, neurological, respiratory, and autoimmune diseases, among others. The pharmaceutical industry has used different technologies to obtain new and promising active ingredients, as exemplified by the fermentation technique, recombinant DNA technique and the hybridoma technique. The expiry of the patents of the first drugs of biotechnological origin and the consequent emergence of biosimilar products, have posed various questions to health authorities worldwide regarding the definition, framework, and requirements for authorization to market such products.

Nos últimos anos, tem aumentado exponencialmente o número de fármacos de origem biotecnológica ao dispor das mais diversas patologias, entre elas destacam-se, os diferentes tipos de cancêr, as doenças infecciosas (ex. vírus AIDS/HIV), as doenças autoimunes, as doenças cardiovasculares, a Diabetes Mellitus, as doenças neurológicas, as doenças respiratórias, entre outras. A indústria farmacêutica tem recorrido a diferentes tecnologias para a obtenção de novos e promissores princípios ativos, como são exemplo a fermentação, a técnica de DNA Recombinante, a técnica de hidridoma, entre outras. A queda das patentes dos primeiros fármacos de origem biotecnológica e o consequente aparecimento dos produtos biossimilares têm colocado diferentes questões às autoridades de saúde mundiais, sobre a definição, enquadramento e exigências para a autorização de entrada no mercado deste tipo de produtos.