Quality by Design (QbD) principles have been adopted by pharmaceutical industries with the aim of improving the understanding of processes and products and thus improving product quality and regulatory flexibility. A key component of QbD is Design Space (DS), defined as the multidimensional combination of the input variables where the assurance of quality is provided. QbD has been recently attracting attention in the development of analytical separation methods. The aim of this study is the application of QbD approach in the development of a capillary electrophoresis (CE) method for the simultaneous determination of almotriptan, used for the acute treatment of migraine attacks, and its main impurities. The analytical target profile of the method was the baseline separation of all the peaks, with LOQ values for the impurities equal to or lower than 0.1% with respect to the active pharmaceutical ingredient. Control quality attributes (CQAs) were defined as resolution values of critical peak pairs and analysis time. A scouting study including several CE operative modes was carried out, and microemulsion electrokinetic chromatography (MEEKC) led to the best results. In MEEKC the background electrolyte is a microemulsion, which is a stable system containing oil and water, stabilized by a surfactant and a co-surfactant. The performance of the MEEKC run depends both on the proportions of mixture components (MCs) of the microemulsion and on the values of process variables (PVs). Knowledge space on the PVs was investigated by means of an asymmetric screening matrix. Then, a mixture-process variable approach, which simultaneously varies MCs and PVs, was applied. Monte-Carlo simulations were performed to include uncertainty of the parameters of the models and to estimate the probability of meeting the specifications imposed on the CQAs, and allowed the DS to be defined by means of risk of failure maps. Finally, a control strategy based on system suitability tests was implemented.
Innovative capillary electrophoresis method development for the determination of almotriptan and its impurities: Quality by Design approach / S. Furlanetto; S. Orlandini; B. Pasquini; S. Pinzauti. - ELETTRONICO. - (2013), pp. 53-53. (Intervento presentato al convegno XXIV Congresso della Divisione di Chimica Analitica della Società Chimica Italiana tenutosi a Sestri Levante (Genova) nel 15-19 Settembre 2013).
Innovative capillary electrophoresis method development for the determination of almotriptan and its impurities: Quality by Design approach
FURLANETTO, SANDRA;ORLANDINI, SERENA;PASQUINI, BENEDETTA;PINZAUTI, SERGIO
2013
Abstract
Quality by Design (QbD) principles have been adopted by pharmaceutical industries with the aim of improving the understanding of processes and products and thus improving product quality and regulatory flexibility. A key component of QbD is Design Space (DS), defined as the multidimensional combination of the input variables where the assurance of quality is provided. QbD has been recently attracting attention in the development of analytical separation methods. The aim of this study is the application of QbD approach in the development of a capillary electrophoresis (CE) method for the simultaneous determination of almotriptan, used for the acute treatment of migraine attacks, and its main impurities. The analytical target profile of the method was the baseline separation of all the peaks, with LOQ values for the impurities equal to or lower than 0.1% with respect to the active pharmaceutical ingredient. Control quality attributes (CQAs) were defined as resolution values of critical peak pairs and analysis time. A scouting study including several CE operative modes was carried out, and microemulsion electrokinetic chromatography (MEEKC) led to the best results. In MEEKC the background electrolyte is a microemulsion, which is a stable system containing oil and water, stabilized by a surfactant and a co-surfactant. The performance of the MEEKC run depends both on the proportions of mixture components (MCs) of the microemulsion and on the values of process variables (PVs). Knowledge space on the PVs was investigated by means of an asymmetric screening matrix. Then, a mixture-process variable approach, which simultaneously varies MCs and PVs, was applied. Monte-Carlo simulations were performed to include uncertainty of the parameters of the models and to estimate the probability of meeting the specifications imposed on the CQAs, and allowed the DS to be defined by means of risk of failure maps. Finally, a control strategy based on system suitability tests was implemented.
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