Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-06-14T13:50:33Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Leandro Medeiros_FINAL.pdf: 5085609 bytes, checksum: b4b5384d5a53a32e77af352167a47410 (MD5) / Made available in DSpace on 2016-06-14T13:50:33Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Leandro Medeiros_FINAL.pdf: 5085609 bytes, checksum: b4b5384d5a53a32e77af352167a47410 (MD5) Previous issue date: 2013-02-26 / CNPq / A hipovitaminose D é um estado de carência nutricional da vitamina D que possui uma prevalência estimada em aproximadamente um bilhão de pessoas em todo o mundo. Há evidências que do ponto de vista de intervenção medicamentosa, o colecalciferol pode exercer efeito preventivo, paliativo e/ou terapêutico, em doenças crônicas não transmissíveis, em monoterapia e com dosagens muito acima das estabelecidas como nutricionais (até 100.000 UI/dose), e nesse contexto, caracterizando como nutracêutico. Pela disponibilidade no mercado nacional com tais especificações farmacêuticas apenas em farmácias de manipulação e pela necessidade de mais estudos clínicos com propósito de avaliar seu potencial nutracêutico, este estudo teve como objetivo o desenvolvimento farmacotécnico magistral de cápsulas gelatinosas duras com colecalciferol (100.000 UI / dose) e comparar sua qualidade frente a produtos manipulados em farmácias do município do Recife. Foram realizados testes de caracterização física e físico-química do insumo farmacêutico ativo (descrição macroscópica; caracterização térmica e determinação de pureza; obtenção de cinética de degradação não isoterma; caracterização por infravermelho; difração de raios X; microscopia eletrônica de varredura; análise granulométrica; ângulo de repouso e velocidade de escoamento), os quais se apresentaram conforme com especificações farmacopeicas. Em seguida, foi realizado um teste de solubilidade qualiquantitativa para dar fundamentação experimental aos testes de dissolução, no qual foi escolhido como meio de melhor eficiência (pH = 6,8 com lecitina de soja [0,75mM]). Por métodos termogravimétricos, foram realizados testes de compatibilidade fármaco – excipiente e os excipientes qualitativamente escolhidos foram butil-hidroxitolueno, lactose monoidratada e celulose microcristalina. Através do conceito de planejamento fatorial, foram obtidos nove lotes de bancada, os quais tiveram sua composição variada quantitativamente. Os testes de controle de qualidade demonstraram que todos foram aprovados nos testes de umidade, peso médio e desintegração, porém apenas três foram aprovados no teste de doseamento. O desenvolvimento do método de dissolução apresentou-se inviável por espectrofotometria na região do UV-vis, dada a não reprodutibilidade dos resultados obtidos. Apenas um dos lotes das farmácias apresentou doseamento dentro da faixa aceitável. Diante da impossibilidade do desenvolvimento de um método de dissolução, não foi possível a realização desta etapa de controle de qualidade e, portanto, mais estudos são necessários para sua conclusão. / Hypovitaminosis D is a nutritional deficiency state of vitamin D, which has prevalence, estimated at about one billion people around the world. There is evidence that, in a pharmacologic context, the cholecalciferol can exert a preventive, palliative and/or therapeutic effect, in non-transmissible chronic diseases, in doses that exceed that considered as food (up to 100,000 IU/dose), and in this context, characterizing it as nutraceutical. Due to the availability in the Brazilian market with such pharmaceutical specifications, only by compounding pharmacies and the need for more clinical studies with purpose to assess their potential nutraceutical, this study aimed the compounding hard capsules pharmacotechnical development with cholecalciferol (100,000 IU/dose) and compare their quality against the products handled in pharmacies in the city of Recife. Physical and physicochemical characterization tests of drug (macroscopic description; thermal characterization and determination of purity; obtaining kinetics of degradation non isotherm; infrared; characterization x-ray diffraction; scanning electron microscopy particle size analysis; rest angle and flow rate) presented themselves according pharmacopeia specifications. There was conducted a quantitative solubility test to give experimental substantiation of dissolution tests, and the most efficiently medium chosen was with pH 6.8 plus soy lecithin [0, 75 mM]). By thermogravimetrics analysis, tests of drug-excipient compatibility and the excipients qualitatively chosen were butylated hydroxytoluene, lactose and microcrystalline cellulose. Applying the concept of factorial planning, were obtained nine experimental lots, which had its composition varied quantitatively. Quality control tests showed that all lots were approved in testing loss for desiccation, average weight and disintegration, but only four lots were approved by quantification analytical method. The development of the dissolution method was infeasible by spectrophotometry in the UV-vis, given the non-reproducibility of the results obtained. Only one of compounding pharmacies showed quantification within the acceptable range. Faced with the impossibility of developing a method of dissolution, it has not been possible to achieve this stage of quality control and, therefore, further studies are needed for its completion.

Comme plusieurs pays du monde, Madagascar a fait rentrer dans sa politique de santé, l’utilisation des médicaments génériques, de moindre coût, pour faciliter l’accès aux soins de la population. La promotion des médicaments génériques impose de garantir leur qualité par rapport aux médicaments de référence. Une étude a été menée pour contribuer à l’amélioration des pratiques du système de réglementation et des contrôles pharmaceutiques de Madagascar. Pour cela, l’environnement pharmaceutique et le système d’enregistrement des médicaments de ce pays sont présentés en regard de ceux existants dans d’autres pays. Ensuite, des contrôles de qualité englobant des essais physico-chimiques, pharmaco-techniques et pharmacologiques, sont réalisés sur vingt-deux médicaments antihypertenseurs dont quatre spécialités de références et dix-huit spécialités considérées comme leurs génériques, échantillonnés à Madagascar. L’augmentation incessante du nombre de malades atteints d’hypertension artérielle, couplée avec la difficulté de son traitement, sont à l’origine du choix de la famille thérapeutique étudiée. Pour les dix-huit spécialités considérées comme génériques, des non conformités aux référentiels ont été révélées. Seulement une spécialité considérée comme générique a présenté des caractéristiques, dont la cinétique de dissolution et les résultats pharmacologiques, similaires à celles de la référence. Des préconisations impliquant tous les acteurs du domaine pharmaceutiques ont pu être dégagées à partir de l’étude. / Like many countries in the world, Madagascar has returned in its health policy, the use of generic drugs, because of their lower cost, to facilitate access to health care of the population. The promotion of generic drugs needs to ensure their quality compared to reference drugs. A study was conducted to contribute to the improvement of practices and drug regulatory system in Madagascar . For this, the pharmaceutical environment and the registration of generic drugs in this country with those of other countries are presented. Then quality control tests were performed on twenty two antihypertensive drugs including four referent specialties and eighteen specialties considered as their generic, sampled in Madagascar . The choice of this therapeutic family was governed by the constant increase in the number of patients suffering from hypertension, associated with the difficulty of treatment. For the eighteen specialties considered as generics, non-compliances with standards were recorded at the end of the physicochemical and pharmacotechnical tests and pharmacological studies. Only one specialty was shown to present similar characteristics, including dissolution kinetics and pharmacological results, as the reference. Recommendations involving all stakeholders of the pharmaceutical field have been brought from the study.