Optimization of a new dissolution test for oxcarbazepine capsules using mixed-level factorial design

Abstract

Neste trabalho foi desenvolvido e validado um teste de dissolução para cápsulas de oxcarbazepina. Para o estudo de triagem, foi utilizado um planejamento experimental de níveis mistos composto de fatores com dois e três níveis (3 2 × 2), de modo a selecionar a velocidade de agitação, o meio de dissolução e o aparato. Esta estratégia é útil, pois reduz o tempo de desenvolvimento do método e também gera resultados mais exatos. A melhor porcentagem de dissolução foi obtida utilizando o aparato pá a 80 rpm e com solução aquosa de laurilsulfato de sódio a 1% m/v como meio de dissolução. A quantificação da massa dissolvida foi realizada por análise espectrofotométrica UV-Vis a 304 nm. Os resultados do estudo da validação demonstraram que o método é preciso e linear no intervalo de 83-249 μg mL -1 de oxcarbazepina. Os resultados evidenciaram que o método apresenta utilidade e adequabilidade para o estudo da dissolução de cápsulas de oxcarbazepina, uma vez que não existe método oficial com este propósito.In this work, a dissolution test for oxcarbazepine capsules was developed and validated. For the screening study, a mixed-level factorial design containing factors at three and two levels (3 2 × 2) was used in order to select the stirring speed, the dissolution medium and the dissolution apparatus. This strategy is needful for reducing the time of method development and to provide less ambiguous data. The best in vitro percentage dissolution was obtained using apparatus paddle at 80 rpm and sodium lauryl sulfate 1% m/v aqueous solution as the dissolution medium. The quantification of the mass dissolved was obtained by UV-Vis spectrophotometric analysis at 304 nm. The validation results demonstrate that the method was precise and linear over the range of 83-249 μg mL -1 of oxcarbazepine. Thus, the method is useful and adequate for oxcarbazepine capsules dissolution test, once there is no official monograph regarding it. Keywords: oxcarbazepine, dissolution test, mixed-level factorial design IntroductionOxcarbazepine (OCBZ) (Figure 1) is a keto analog of carbamazepine 1 indicated as monotherapy or adjunctive therapy for the treatment of partial seizures with or without secondarily generalized tonic-clonic seizures in adults and children aged over six years. 2,3 The advantages of OCBZ on carbamazepine are: lower frequency and severity of adverse events (particularly endocrine), [4][5][6] better tolerability, 3,6 fewer drug interactions 7 and almost complete absorption after oral ingestion. 3 Another point is that OCBZ is a low therapeutic index, high dosage and low potency drug. Its compounding and marketing, therefore, can only be made if the performance of the formulation is proved by conducting the dissolution test of the final product. Optimization of a New Dissolution Test for Oxcarbazepine Capsules J. Braz. Chem. Soc. 1264 Dissolution tests have become a highly valuable tool for quality analysis in the pharmaceutical industry in what concerns the performance of the oral solid dosage form/delivery system, 9,10 bec...

Laboratory Glassware Cleaning Validation by Liquid Chromatographic Quantitation of Betamethasone Valerate Residues

“…Pharmaceutical firms are expected to maintain laboratory glassware in a clean and sanitary manner to provide confidence in the analytical results (Pluta, 2007). It is therefore important to demonstrate the efficiency of glassware cleaning procedure through a validation program (Polonini et al, 2011;Sandale et al, 2016). The objective of cleaning efficiency testing is to provide the evidence that the glassware is consistently cleaned of product, to prevent possible crosscontamination (General European QM document, Polonini et al, 2011).…”