Endotoxin test by recombinant Factor C for 0.9% sodium chloride injection

Endotoxin contamination is a threat to the safety of pharmaceutical products, especially parenteral drugs. Any sterile and/or pyrogen-free pharmaceutical product requires regulatory specifications to ensure safe patient use. This study covers the performance evaluation study of an endotoxin quantitation commercial kit by recombinant Factor C (rFC), Endozyme II® Go, for 0.9% sodium chloride injection. The samples were spiked with endotoxin solutions between 0.0005 and 10 EU/mL and tested by the rFC kit to evaluate precision, accuracy, detection and quantification limits, linearity, and robustness. Each of the six points was assayed at least five times.The relative standard deviation for precision testing ranged from 1.9 to 8.3%. The recovery accuracy values of endotoxin were between 61% and 125% for the range from 0.005 to 10 EU/mL. The results demonstrated that the rFC method allows endotoxin quantification with accuracy, precision, specificity, and linearity for the range of 0.005 and 10 EU/mL for 0.9% sodium chloride injection. (AU)

A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral. (AU)

Evaluation of an Amplified ATP Bioluminescence Method for Rapid Sterility Testing of Large Volume Parenteral

The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.

Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test

The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.

Comparison of dissolution profile of extended-release oral dosage forms - two one-sided equivalence test

The aim of this work is to present the two one-sided test (TOST) as an alternative approach to compare dissolution profiles of extended-release dosage forms. The dissolution profiles of oxycodone extended-release tablets containing 10 mg, 20 mg and 40 mg (reference and generic) were evaluated according to the requirements described in United States Pharmacopeia. These dissolution profiles were compared using the conventional similarity factor (f2) and the proposed TOST as an equivalence test. TOST is a simple and alternative approach to compare dissolution profiles of extended-release dosage forms. It allows us to identify the time-point (or time-points) that did not show similarity. We concluded that the two one-sided test performed at a significance level of 5% and defined as D = 10 showed results comparable to those obtained by the conventional similarity factor (f2).

O objetivo deste trabalho é apresentar o teste uni-caudal duplo (TOST) como uma abordagem alternativa na comparação do perfil de dissolução de formas farmacêuticas de liberação prolongada. Os perfis de dissolução de comprimidos de liberação prolongada de oxicodona contendo 10 mg, 20 mg e 40 mg (genérico e referência) foram avaliados de acordo com os requisitos descritos na Farmacopeia Americana. Estes perfis de dissolução foram comparados empregando-se o fator de semelhança convencional (f2) e o método TOST como teste de equivalência. TOST é uma abordagem simples e alternativa para a comparação de perfis de dissolução de formas farmacêuticas de liberação prolongada. Este permite identificar o ponto (ou pontos) que não apresentou semelhança. Considerando-se D = 10, concluímos que o teste uni-caudal duplo num nível de significância de 5% apresenta resultados comparáveis àqueles obtidos com o fator de semelhança convencional (f2).