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Authors
Abstract(s)
Este relatório está organizado em três capítulos, o primeiro referente ao trabalho realizado
para a vertente de investigação científica em Ciências Farmacêuticas, desenvolvido no
Centro de Investigação em Ciências da Saúde da Universidade da Beira Interior, sob a
orientação da Prof.ª Doutora Adriana Oliveira dos Santos e que diz respeito ao
desenvolvimento e caracterização de uma formulação intranasal de tenivastatina para o
acidente vascular cerebral (AVC) isquémico.
O trabalho aborda o AVC, uma das principais causas de morte e incapacidade em Portugal
e no mundo, focando-se no tipo mais comum, o isquémico. A prevenção é crucial, mas
também é fundamental melhorar o tratamento e a recuperação após um AVC. Atualmente
a administração de medicamentos trombolíticos é o único tratamento disponível e o mesmo
deve ser feito num curto espaço de tempo após o evento. Assim sendo, esta é uma
necessidade médica não adequadamente atendida, pelo que é necessário encontrar novas
terapias e estratégias de reabilitação para ajudar os pacientes a recuperar a sua função
cerebral, minimizando o impacto e custo nas suas vidas. Neste contexto, este estudo
explorou o efeito neuroprotetor já descrito das estatinas, mais especificamente da forma
ativa da sinvastatina, a tenivastatina. No entanto, este grupo de fármacos possui uma
biodisponibilidade oral baixa, devido ao extenso metabolismo hepático de primeira
passagem. Assim, como alternativa, optou-se explorar a sua administração intranasal e
definiram-se algumas características do Perfil de Produto Alvo de Qualidade que se devem
respeitar.
No trabalho foi realizada a hidrólise da sinvastatina para obtenção de uma solução de
tenivastatina, a qual foi adequadamente alterada para ser uma formulação compatível com
a via nasal. Assim, foi feito um ajuste no pH da mesma, cujo resultado obtido apresentou
valores que não prejudicam a mucosa nasal e que se encontram dentro do valor de objetivo
alargado (6 - 8). A osmolalidade da formulação foi também avaliada e isotonizada com
cloreto de sódio. Outro atributo avaliado foi a viscosidade, que foi promovida por adição de
hidroxipropilmetilcelulose. A viscosidade aumentada promove a mucoadesão; contudo,
foram ligeiramente ultrapassados os valores previamente definidos como os ideais para este
tipo de formulação. Também foi aumentada a dosagem de tenivastatina, sendo possível
alcançar valores interessantes para a sua utilização. Para além disto, foi avaliada a
estabilidade química da formulação, a quatro diferentes temperaturas (-20 °C, 4 °C, 25 °C e
40 °C) de armazenamento, por meio de um ensaio de cromatografia líquida acoplado a
deteção ultra-violeta para quantificação de tenivastatina. Os resultados obtidos são
encorajadores a curto prazo (2 meses), principalmente às temperaturas mais baixas (-20 ºC e 4 ºC), para a qual a formulação se mostrou estável. Todos os atributos apresentaram
resultados promissores e devem, por isso, ser alvo de novas investigações. Porém, ainda há
necessidade de continuar este estudo para melhor caracterizar e avaliar a possibilidade
desta formulação poder vir a constituir uma nova alternativa terapêutica segura e eficaz para
o AVC.
O segundo capítulo descreve a minha experiência de estágio curricular em farmácia
comunitária na Farmácia Simões, em Benfica, Lisboa, sob a supervisão e orientação da
farmacêutica adjunta Dr.ª Alexandra Feliciano, no período de 7 de fevereiro a 29 de abril de
2022. Durante este período, tive oportunidade de vivenciar o complexo quotidiano de um
farmacêutico comunitário, enfrentando todos os desafios que esta área apresenta, como a
dispensa e aconselhamento ao utente, bem como a toda a gestão e organização da farmácia.
Este foi um período crucial para a minha aprendizagem e para o desenvolvimento das
minhas competências, proporcionando-me uma visão prática muito enriquecedora do
mundo do trabalho e da responsabilidade desta área.
O terceiro capítulo relata o meu estágio curricular em farmácia hospitalar no Centro
Hospitalar e Universitário Cova da Beira (CHUCB), que decorreu de 4 de maio a 1 de julho
de 2022 com a orientação e supervisão da Doutora Olímpia Fonseca. Nesse período, pude
contactar e experienciar pela primeira vez a rotina de um farmacêutico hospitalar,
acompanhando todos os serviços ali desempenhados de forma multidisciplinar pelos
profissionais de saúde nos diversos setores, como no ambulatório, na distribuição de
medicamentos e na reconciliação da terapêutica. Este estágio foi também uma mais-valia
no meu desenvolvimento e formação académica.
This report is organized into three chapters. The first concerning the work carried out for the scientific research to the masters in Pharmaceutical Sciences, which was developed at the Health Sciences Research Center of the University of Beira Interior under the guidance of Professor Adriana Oliveira dos Santos and which concerns the development and characterization of an intranasal formulation of Tenivastatin for ischemic stroke. The work addresses stroke, one of the main causes of death and disability in Portugal and worldwide, focusing on the most common type, the ischemic. Prevention is crucial, but it’s also critical to improve treatment and recovery after a stroke. Currently, the administration of thrombolytic drugs is the only treatment available and the same should be done in a short time after the event. As so, this is an medical need not adequatly met, so it is necessary to find alternatives for new therapies and rehabilitation strategies to help patients to recover their brain function, minimizing the impact and cost in their lives. In this context, this study explored the already described neuroprotective effect of statins, more specifically the active form of simvastatin, the tenivastatin. However, this group of drugs have a low oral bioavailability, due to extensive first pass metabolism in the liver, so, as an alternative, we opted to study the intranasal administration of tenivastatin and defined some characteristics of the Quality Target Product Profile to be respected. In the work, simvastatin was hydrolyzed to obtain a tenivastatin solution, which was appropriately modified to be a formulation compatible with the nasal route. Therefore, an adjustment was made to it’s pH, the result obtained showing values that do not harm the nasal mucosa and that are within the broad objective value (6 - 8). The osmolality of the formulation was also evaluated and isotonized with sodium chloride. Another attribute evaluated was viscosity, which was promoted by the addition of hydroxypropylmethylcellulose. Increased viscosity promotes mucoadhesion; however, the values previously defined as ideal for this type of formulation were slightly exceeded. The dosage of tenivastatin was also increased, making it possible to reach interesting values for its use. In addition, the chemical stability of the formulation was evaluated at four different storage temperatures (-20 °C, 4 °C, 25 °C and 40 °C), using a high performance liquid chromatography test coupled to ultra-violet detection for tenivastatin quantification. The results obtained are encouraging at short term (2 months), especially at lower temperatures (-20 ºC and 4 ºC), for which the formulation proved to be stable. All attributes showed promising results and should, therefore, be the target of further investigations. However, there is still a need to continue this study to better characterize and evaluate the possibility of this formulation being a new, safe and effective therapeutic alternative for stroke. The second chapter describes my experience of curricular internship in community pharmacy at Farmácia Simões, in Benfica, Lisboa under the supervision and guidance of assistant pharmacist Doctor Alexandra Feliciano, from February 7th to April 29th, 2022. During this period, I had the opportunity to experience the complex daily life of a community pharmacist, facing all the challenges that this area presents, such as dispensing medicines and counseling the patient as well as the entire management and organization of the pharmacy. This was a crucial moment for my learning and for the development of my skills, providing me with a very enriching practical vision of the world of work and the responsibility of this area. The third chapter reports my curricular internship in hospital pharmacy at the Cova da Beira Hospital and University Center, which took place from May 4th to July 1st, 2022 with the guidance and supervision of Doctor Olímpia Fonseca. During this period, I was able to contact and to experience the routine of a hospital pharmacist for the first time, following all the services performed in a multidisciplinary way by health professionals in the different sectors, distribution of medicines and reconciliation of therapy. This internship was an asset in my development and academic training.
This report is organized into three chapters. The first concerning the work carried out for the scientific research to the masters in Pharmaceutical Sciences, which was developed at the Health Sciences Research Center of the University of Beira Interior under the guidance of Professor Adriana Oliveira dos Santos and which concerns the development and characterization of an intranasal formulation of Tenivastatin for ischemic stroke. The work addresses stroke, one of the main causes of death and disability in Portugal and worldwide, focusing on the most common type, the ischemic. Prevention is crucial, but it’s also critical to improve treatment and recovery after a stroke. Currently, the administration of thrombolytic drugs is the only treatment available and the same should be done in a short time after the event. As so, this is an medical need not adequatly met, so it is necessary to find alternatives for new therapies and rehabilitation strategies to help patients to recover their brain function, minimizing the impact and cost in their lives. In this context, this study explored the already described neuroprotective effect of statins, more specifically the active form of simvastatin, the tenivastatin. However, this group of drugs have a low oral bioavailability, due to extensive first pass metabolism in the liver, so, as an alternative, we opted to study the intranasal administration of tenivastatin and defined some characteristics of the Quality Target Product Profile to be respected. In the work, simvastatin was hydrolyzed to obtain a tenivastatin solution, which was appropriately modified to be a formulation compatible with the nasal route. Therefore, an adjustment was made to it’s pH, the result obtained showing values that do not harm the nasal mucosa and that are within the broad objective value (6 - 8). The osmolality of the formulation was also evaluated and isotonized with sodium chloride. Another attribute evaluated was viscosity, which was promoted by the addition of hydroxypropylmethylcellulose. Increased viscosity promotes mucoadhesion; however, the values previously defined as ideal for this type of formulation were slightly exceeded. The dosage of tenivastatin was also increased, making it possible to reach interesting values for its use. In addition, the chemical stability of the formulation was evaluated at four different storage temperatures (-20 °C, 4 °C, 25 °C and 40 °C), using a high performance liquid chromatography test coupled to ultra-violet detection for tenivastatin quantification. The results obtained are encouraging at short term (2 months), especially at lower temperatures (-20 ºC and 4 ºC), for which the formulation proved to be stable. All attributes showed promising results and should, therefore, be the target of further investigations. However, there is still a need to continue this study to better characterize and evaluate the possibility of this formulation being a new, safe and effective therapeutic alternative for stroke. The second chapter describes my experience of curricular internship in community pharmacy at Farmácia Simões, in Benfica, Lisboa under the supervision and guidance of assistant pharmacist Doctor Alexandra Feliciano, from February 7th to April 29th, 2022. During this period, I had the opportunity to experience the complex daily life of a community pharmacist, facing all the challenges that this area presents, such as dispensing medicines and counseling the patient as well as the entire management and organization of the pharmacy. This was a crucial moment for my learning and for the development of my skills, providing me with a very enriching practical vision of the world of work and the responsibility of this area. The third chapter reports my curricular internship in hospital pharmacy at the Cova da Beira Hospital and University Center, which took place from May 4th to July 1st, 2022 with the guidance and supervision of Doctor Olímpia Fonseca. During this period, I was able to contact and to experience the routine of a hospital pharmacist for the first time, following all the services performed in a multidisciplinary way by health professionals in the different sectors, distribution of medicines and reconciliation of therapy. This internship was an asset in my development and academic training.
Description
Keywords
Acidente Vascular Cerebral Isquémico Administração
Intranasal Estabilidade Farmácia Comunitária Farmácia Hospitalar Formulação de Tenivastatina