Estudo de solubilidade e ensaio preliminar do perfil de dissolução do fármaco nitazoxanida em suspensão oral

A nitazoxanida, um pró-fármaco de amplo espectro utilizado em infecções parasitárias, é comercializada em duas formas farmacêuticas: comprimidos revestidos de 500 mg e pó para suspensão oral de 20 mg/mL. Hoje, com a lei dos genéricos, além do medicamento de referência, Annita®, há também disponível no mercado as opções Nitazoxanida e Azox®. Com a presença de outras formulações além da de referência no mercado, é importante um rigoroso controle de qualidade para assegurar a eficácia e segurança dessas formulações. A nitazoxanida já possui monografia na 6° ed da Farmacopeia Brasileira, o que serve para direcionar os testes a serem feitos para realizar esse controle de qualidade, entretanto, observa-se que para a Nitazoxanida Suspensão oral não há um teste de perfil de dissolução. Sabendo da importância de traçar um perfil de dissolução para fins de comparação entre referência e genéricos, e visto a ausência de um método com este propósito na Farmacopeia, o trabalho teve como objetivo o desenvolvimento de um método de perfil de dissolução de Nitazoxanida suspensão oral. No decorrer do trabalho foram testadas diversas condições e o método com melhores resultados foi em meio tampão fosfato pH 7,4 e 5% de CPC, com agitação de 100 rpm, temperatura de banho de 37 °C, filtros com porosidade de 35 μm, tempo total de dissolução de 120 minutos e quantificação por CLAE

Microbiological assay for quantitative determination of Imipenem in powder for injection

This work describes the development and validation of a microbiological method using the cylinder-plate assay for quantitative determination of imipenem in powder for injection. The aim was to obtain a low-cost and suitable methodology that can be alternative to physicochemical techniques already described, contributing for the quality control of this antibiotic. Firstly, the analytical conditions were optimized, testing the microorganism, inoculum concentration and best range of sample and standard concentrations, in a way that provides the adequate measurement of the inhibition halos. Staphylococcus epidermidis ATCC 12228 was selected as test microorganism, as well as 2.0 % of inoculum concentration. The validation protocol followed the official guidelines, and the parameters evaluated were linearity, precision (intermediate precision and repeatability) and accuracy. All standard curves ranging 0.5-2.0 μg/mL showed r values higher than 0.999, and ANOVA confirmed that were no deviation from linearity (p-value > 0.05). The method also proved to be precise with RSD (relative standard deviation) values ranging 0.28-0.64 for repeatability and 2.49 for intermediate precision. It was performed three days of experiments, being three assays of eight plates a day. The drug mean content was 101.05%. Accuracy was assessed by recovery test, with standard recovery percentage of 101.70-107.90% (mean recovery = 104.86%), which was considered satisfactory. Therefore, the proposed microbiological method was considered validated and suitable for application in quantitative determination of this drug, being useful for quality control routine

pH effect on stability and kinetics degradation of nitazoxanide in solution

Stability studies correspond to a set of tests designed to assess changes in the quality of a given drug over time and under the influence of a number of factors. Among these factors, pH plays an important role, due to the catalytic effect that hydronium and hydroxide ions can play in several reactions. In the present study, the degradation kinetics of nitazoxanide was evaluated over a wide pH range, and the main degradation product generated was identified by LC-MS/MS. Nitazoxanide showed first-order degradation kinetics in the pH range of 0.01 to 10.0 showing greater stability between pH 1.0 and 4.0. The degradation rate constant calculated for these pH was 0.0885 x 10-2 min-1 and 0.0689 x 10-2 min-1, respectively. The highest degradation rate constant value was observed at pH 10.0 (0.7418 x 10-2 min-1) followed by pH 0.01 (0.5882 x 10-2 min-1). A major degradation product (DP-1) was observed in all conditions tested. Through LC-MS/MS analysis, DP-1 was identified as a product of nitazoxanide deacetylation. The effect of pH on the stability of nitazoxanide and the kinetic data obtained contribute to a better understanding of the intrinsic stability characteristics of nitazoxanide

Microbiological assay for quantitative determination of Imipenem in powder for injection

This work describes the development and validation of a microbiological method using the cylinder-plate assay for quantitative determination of imipenem in powder for injection. The aim was to obtain a low-cost and suitable methodology that can be alternative to physicochemical techniques already described, contributing for the quality control of this antibiotic. Firstly, the analytical conditions were optimized, testing the microorganism, inoculum concentration and best range of sample and standard concentrations, in a way that provides the adequate measurement of the inhibition halos. Staphylococcus epidermidis ATCC 12228 was selected as test microorganism, as well as 2.0 % of inoculum concentration. The validation protocol followed the official guidelines, and the parameters evaluated were linearity, precision (intermediate precision and repeatability) and accuracy. All standard curves ranging 0.5-2.0 μg/mL showed r values higher than 0.999, and ANOVA confirmed that were no deviation from linearity (p-value > 0.05). The method also proved to be precise with RSD (relative standard deviation) values ranging 0.28-0.64 for repeatability and 2.49 for intermediate precision. It was performed three days of experiments, being three assays of eight plates a day. The drug mean content was 101.05%. Accuracy was assessed by recovery test, with standard recovery percentage of 101.70-107.90% (mean recovery = 104.86%), which was considered satisfactory. Therefore, the proposed microbiological method was considered validated and suitable for application in quantitative determination of this drug, being useful for quality control routine

MICROBIOLOGICAL ASSAY FOR QUANTITATIVE DETERMINATION OF IMIPENEM IN POWDER FOR INJECTION

This work describes the development and validation of a microbiological method using the cylinder-plate assay for quantitative determination of imipenem in powder for injection. The aim was to obtain a low-cost and suitable methodology that can be alternative to physicochemical techniques already described, contributing for the quality control of this antibiotic. Firstly, the analytical conditions were optimized, testing the microorganism, inoculum concentration and best range of sample and standard concentrations, in a way that provides the adequate measurement of the inhibition halos. Staphylococcus epidermidis ATCC 12228 was selected as test microorganism, as well as 2.0 % of inoculum concentration. The validation protocol followed the official guidelines, and the parameters evaluated were linearity, precision (intermediate precision and repeatability) and accuracy. All standard curves ranging 0.5-2.0 µg mL-1 showed r values higher than 0.999, and ANOVA confirmed that were no deviation from linearity (p-value < 0.05). The method also proved to be precise with RSD (relative standard deviation) values ranging 0.28-0.64 for repeatability and 2.49 for intermediate precision. It was performed three days of experiments, being three assays of eight plates a day. The drug mean content was 101.05%. Accuracy was assessed by recovery test, with standard recovery percentage of 101.70-107.90% (mean recovery = 104.86%), which was considered satisfactory. Therefore, the proposed microbiological method was considered validated and suitable for application in quantitative determination of this drug, being useful for quality control routine

pH effect on stability and kinetics degradation of nitazoxanide in solution

Stability studies correspond to a set of tests designed to assess changes in the quality of a given drug over time and under the influence of a number of factors. Among these factors, pH plays an important role, due to the catalytic effect that hydronium and hydroxide ions can play in several reactions. In the present study, the degradation kinetics of nitazoxanide was evaluated over a wide pH range, and the main degradation product generated was identified by LC-MS/MS. Nitazoxanide showed first-order degradation kinetics in the pH range of 0.01 to 10.0 showing greater stability between pH 1.0 and 4.0. The degradation rate constant calculated for these pH was 0.0885 x 10-2 min-1 and 0.0689 x 10-2 min-1, respectively. The highest degradation rate constant value was observed at pH 10.0 (0.7418 x 10-2 min-1) followed by pH 0.01 (0.5882 x 10-2 min-1). A major degradation product (DP-1) was observed in all conditions tested. Through LC-MS/MS analysis, DP-1 was identified as a product of nitazoxanide deacetylation. The effect of pH on the stability of nitazoxanide and the kinetic data obtained contribute to a better understanding of the intrinsic stability characteristics of nitazoxanide