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Previous issue date: 2017-03-29 / O Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A Organiza??o Mundial de Sa?de (OMS) sugere que o tratamento da tuberculose (TB) seja realizado atrav?s da terapia que consiste na associa??o de quatro f?rmacos: rifampicina, isoniazida, pirazinamida e etambutol. Com isso o tratamento ? melhor aceito tendo uma maior ades?o do paciente ? terapia prescrita. Levando-se em considera??o que a metodologia utilizada para o doseamento de um f?rmaco na presen?a de excipientes e outros f?rmacos ? a cromatografia l?quida de alta efici?ncia (CLAE) que ? sabidamente trabalhosa, de alto custo e destrutiva, foi proposta desse trabalho o desenvolvimento e valida??o de um modelo de calibra??o multivariada em associa??o com a t?cnica de espectroscopia no infravermelho pr?ximo (NIR) para determina??o simult?nea de rifampicina, isoniazida, pirazinamida e etambutol que fosse mais simples, r?pida, de baixo custo, n?o destrutiva e que n?o utilizasse solventes org?nicos, contribuindo assim com o meio ambiente. Sendo, portanto, ferramenta de otimiza??o para o controle de qualidade deste medicamento. Nesse trabalho foi utilizado o m?todo por NIR ? PLS (regress?o de m?nimos quadrados parciais) onde as misturas dos quatro f?rmacos foram realizadas com base no planejamento experimental do tipo composto central elaborado pelo programa Statistica 13 (StatSoft Inc.). Essas misturas foram lidas na faixa de 10.000 a 4.000 cm-1 utilizando um espectrofot?metro Infravermelho (IRPrestige-21 - Shimadzu) com resolu??o de 4 cm-1, 20 varreduras, temperatura e umidade controladas. As an?lises envolvendo CLAE foram realizadas em um cromat?grafo (Hitachi ? Elite Ultra), equipado com coluna C18 (15 cm x 4,6 mm ? ACE-5) e (25 cm x 4,6 mm ? Luna - Phenomenex) e detector UV (matriz de diodo), utilizando o m?todo de refer?ncia descrito na farmacopeia internacional 15? edi??o. Ao final, todos os dados foram tratados por ferramentas computacionais de an?lise multivariada, utilizando PLS atrav?s do programa pirouette 3.11 (Infometrix, Inc.). As sele??es de vari?veis foram realizadas pelo programa QSAR modeling. Foi realizada valida??o cruzada pelo m?todo leave-one-out e estimativa de figuras de m?rito como linearidade, precis?o e exatid?o foram demonstradas nos quatro modelos propostos. Na avalia??o das amostras comerciais pelos modelos de calibra??o multivariada em associa??o com a espectroscopia no infravermelho pr?ximo (NIR) desenvolvidos foram capazes de determinar simultaneamente os quatro f?rmacos, apresentando dados estatisticamente equivalentes aos obtidos por CLAE. / The World Health Organization (WHO) suggests that treatment of tuberculosis (TB) should be done through a combination of four drugs: rifampicin, isoniazid, pyrazinamide and ethambutol. With this the treatment is better accepted having a greater adhesion of the patient to the prescribed therapy. Taking into account that the methodology used for the determination of a drug in the presence of excipients and other drugs is high-performance liquid chromatography (HPLC), which is known to be laborious, expensive and destructive. Validation of a multivariate calibration model in association with the near infrared spectroscopy (NIR) technique for the simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol that was simpler, faster, low cost, non destructive and did not use organic solventes, thus contributing to the environment. Therefore, it is an optimization tool for the quality control of this medicine. In this work, the NIR - PLS (partial least squares regression) method was used where the mixtures of the four drugs were performed based on the experimental design of the central composite type elaborated by the program Statistica 13 (StatSoft Inc.). These mixtures were read in the 10,000 to 4,000 cm-1 range using an infrared (IRPrestige-21 - Shimadzu) spectrophotometer with 4 cm-1 resolution, 20 sweeps, controlled temperature and humidity. The analyzes involving HPLC were performed in a chromatograph (Hitachi - Elite Ultra) equipped with a C18 column (15 cm x 4.6 mm - ACE - 5) and (25 cm x 4.6 mm - Luna - Phenomenex) and UV detector (Diode array) using the reference method described in the International Pharmacopoeia 15th Edition. At the end, all data were treated by computational tools of multivariate analysis, using PLS through the program pirouette 3.11 (Infometrix, Inc.). The selections of variables were performed by the QSAR modeling program. Cross-validation was performed by the leave-one-out method and estimation of merit figures such as linearity, precision and accuracy were demonstrated in the four proposed models. In the evaluation of the commercial samples by the multivariate calibration models in association with the near infrared spectroscopy (NIR), they were able to simultaneously determine the four drugs, presenting data statistically equivalent to those obtained by HPLC.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/24951 |
| Date | 29 March 2017 |
| Creators | Teixeira, Kelly Sivocy Sampaio |
| Contributors | 13138863434, Silva, Henrique Eduardo Bezerra da, 48102288434, Lopes, Gisele Simone, 15114251805, Fonseca, Said Gon?alves da Cruz, 23023490325, Barbosa, Euz?bio Guimar?es, Moura, Tulio Fl?vio Accioly de Lima e |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM DESENVOLVIMENTO E INOVA??O TECNOL?GICA EM MEDICAMENTOS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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