The Creation of an Excipient Properties Database to Support Quality by Design (QbD) Formulation Development

摘要

Under the U.S. FDA's 21st-century Quality Initiative, formulators are encouraged to use the Quality by Design (QbD) approach to develop robust formulations and processes [1]. The adoption of QbD principles by the pharmaceutical industry has led to growing awareness of the profound influence that variability in excipient properties can have on quality and product consistency of finished dosage forms. Accounting for excipient variability is an essential part of the risk assessment needed to define the design space [2]. Excipients are synthetically made, derived from natural products or synthetically modified natural products, and are available from multiple vendors. As a result, their physical/chemical properties can vary from lot to lot and vendor to vendor. Excipient variability has been studied and, in some cases, found to have a significant effect on finished product quality. For example, Barra et al. examined the physiochemical properties and lubricity of 13 lots of Mg stearate (MgSt) from three different vendors [3].They found that MgSt supplied by different vendors are unlikely to have the same physical properties, and variations in physical properties can be expected within lots supplied by the same vendor. The mean particle size of MgSt was found to be the key factor influencing its lubricant efficiency.