Analytical methods used for the determination of active pharmaceutical ingredients and drug products are an integral part of the Quality by Design (QbD) concept that is outlined in ICH Guideline Q8 for pharmaceutical development [1]. The method used for analysis should meet its intended purpose similar to the product requirements for a clinical dosage form [2]. The application of QbD leads to the definition of Design Space (DS), a multidimensional space, which includes any combination of the variables that have been demonstrated to provide assurance of quality of the data produced by the method [2]. A solvent-modified micellar electrokinetic chromatography method was developed for the simultaneous analysis of the tricyclic antidepressant amitriptyline (AMI) and its main impurities. In a scouting phase, a suitable pseudostationary phase was selected. Screening experimental design strategies were then applied for investigating knowledge space. Critical process parameters were represented by the process variables voltage, temperature, buffer concentration and pH, concentration of the surfactant, of the cosurfactant and of the organic modifiers. The critical quality attributes (CQAs) investigated were critical resolution values and analysis time. The DS was finally identified by Response Surface Methodology as the multidimensional combination of variables where the probability for the different considered CQAs to be acceptable was higher than a defined quality level. The developed method was validated and applied to AMI tablets.
Quality by Design approach towards the Design Space definition in the development of a solvent-modified electrokinetic chromatography method / Benedetta Pasquini; Serena Orlandini; Massimo Del Bubba; Sergio Pinzauti; Sandra Furlanetto. - ELETTRONICO. - (2013), pp. 28-28. (Intervento presentato al convegno Incontri di Scienza delle Separazioni tenutosi a Messina nel 28-29 Novembre 2013).
Quality by Design approach towards the Design Space definition in the development of a solvent-modified electrokinetic chromatography method
PASQUINI, BENEDETTA;ORLANDINI, SERENA;DEL BUBBA, MASSIMO;PINZAUTI, SERGIO;FURLANETTO, SANDRA
2013
Abstract
Analytical methods used for the determination of active pharmaceutical ingredients and drug products are an integral part of the Quality by Design (QbD) concept that is outlined in ICH Guideline Q8 for pharmaceutical development [1]. The method used for analysis should meet its intended purpose similar to the product requirements for a clinical dosage form [2]. The application of QbD leads to the definition of Design Space (DS), a multidimensional space, which includes any combination of the variables that have been demonstrated to provide assurance of quality of the data produced by the method [2]. A solvent-modified micellar electrokinetic chromatography method was developed for the simultaneous analysis of the tricyclic antidepressant amitriptyline (AMI) and its main impurities. In a scouting phase, a suitable pseudostationary phase was selected. Screening experimental design strategies were then applied for investigating knowledge space. Critical process parameters were represented by the process variables voltage, temperature, buffer concentration and pH, concentration of the surfactant, of the cosurfactant and of the organic modifiers. The critical quality attributes (CQAs) investigated were critical resolution values and analysis time. The DS was finally identified by Response Surface Methodology as the multidimensional combination of variables where the probability for the different considered CQAs to be acceptable was higher than a defined quality level. The developed method was validated and applied to AMI tablets.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.