Development of a method of analysis for profiling of the impurities in phenoxymethylpenicillin potassium based on the analytical quality by design concept combined with the degradation mechanism of penicillins.

Accurate analysis of all of the impurities present in a substance is critical for controlling the impurity profiles of drugs. Penicillins can easily yield a formidable array of degradation-related impurities (DRIs) with significantly different polarities and charge properties, which renders identifying each one a complicated matter. In this work, phenoxymethylpenicillin potassium (Pen V) was selected to find a way to quickly establish a robust analysis method for the impurity profiling of penicillin. Based on the analytical quality by design (AQbD) concept and the degradation mechanism of the drug, structures of all of the DRIs were first proposed. Then Pen V and its detected DRIs were separated and identified by liquid chromatography-tandem mass spectrometry method (LC-MS). Characteristic fragment ions and mass fragmentation process of Pen V and its detected DRIs were summarized. In addition, a quantitative structure-retention relationship (QSRR) model was constructed to predict the retention times of undetected impurities and to evaluate whether the chromatographic system can separate them. Finally, a stability-indicating high-performance liquid chromatography (HPLC) method was developed that can separate all of the DRIs of Pen V.

Multi-analyte quantification in bioprocesses by Fourier-transform-infrared spectroscopy by partial least squares regression and multivariate curve resolution.

This paper presents the quantification of Penicillin V and phenoxyacetic acid, a precursor, inline during Pencillium chrysogenum fermentations by FTIR spectroscopy and partial least squares (PLS) regression and multivariate curve resolution - alternating least squares (MCR-ALS). First, the applicability of an attenuated total reflection FTIR fiber optic probe was assessed offline by measuring standards of the analytes of interest and investigating matrix effects of the fermentation broth. Then measurements were performed inline during four fed-batch fermentations with online HPLC for the determination of Penicillin V and phenoxyacetic acid as reference analysis. PLS and MCR-ALS models were built using these data and validated by comparison of single analyte spectra with the selectivity ratio of the PLS models and the extracted spectral traces of the MCR-ALS models, respectively. The achieved root mean square errors of cross-validation for the PLS regressions were 0.22 g L(-1) for Penicillin V and 0.32 g L(-1) for phenoxyacetic acid and the root mean square errors of prediction for MCR-ALS were 0.23 g L(-1) for Penicillin V and 0.15 g L(-1) for phenoxyacetic acid. A general work-flow for building and assessing chemometric regression models for the quantification of multiple analytes in bioprocesses by FTIR spectroscopy is given.

Desarrollo Tecnológico de la Formulación de Fenoximetilpenicilina, Cápsula 250 mg / Technological develpment of the phenoxymethylpenicillin formulation, capsules 250 mg

La fenoximetilpenicilina es un antibiótico ß-lactámico que tiene actividad antimicrobiana similar a la bencilpenicilina; su uso está indicado en el tratamiento de infecciones benignas o moderadamente graves. Se describe el desarrollo de la tecnología de formulación de fenoximetilpenicilina, cápsulas de 250 mg, a partir de la elaboración del granulado mediante el método de la vía seca, mezclando el principio activo con los excipientes necesarios para lograr un producto final que cumpla con las características que lo hacen adecuado para su uso. El producto obtenido fue conservado a temperatura controlada y se realizó el estudio de estabilidad, determinándose el tiempo de vida útil para esta formulación. El medicamento diseñado cumple con los requerimientos más actuales para su comercialización y posee beneficios sociales y económicos elevados(AU)

Desarrollo Tecnológico de la Formulación de Fenoximetilpenicilina, Cápsula 250 mg / Technological develpment of the phenoxymethylpenicillin formulation, capsules 250 mg

La fenoximetilpenicilina es un antibiótico ß-lactámico que tiene actividad antimicrobiana similar a la bencilpenicilina; su uso está indicado en el tratamiento de infecciones benignas o moderadamente graves. Se describe el desarrollo de la tecnología de formulación de fenoximetilpenicilina, cápsulas de 250 mg, a partir de la elaboración del granulado mediante el método de la vía seca, mezclando el principio activo con los excipientes necesarios para lograr un producto final que cumpla con las características que lo hacen adecuado para su uso. El producto obtenido fue conservado a temperatura controlada y se realizó el estudio de estabilidad, determinándose el tiempo de vida útil para esta formulación. El medicamento diseñado cumple con los requerimientos más actuales para su comercialización y posee beneficios sociales y económicos elevados