Predictive in vitro dissolution tools : application during formulation development

Dissolution has emerged as a key method during development of medicines and for quality control of marketed products. At the early stage of development, dissolution guides the selection of toxicology and first test in man formulations. At later stages of development, dissolution tests are performed to compare prototype formulations, the robustness of the manufacturing process, to indicate stability and to assure safe release and reproductibility of the products to the market. However despite they wide use in pharmaceutical development, several challenges still exist. In particular, there is a lack of thorough identification and understanding of the critical quality attributes that control dissolution of Active Pharmaceutical Ingredient and Drug Product. Dissolution exhibits clearly a higher predictability if it can be extrapolated directly to in vivo behavior. Thepresent work focuses on the optimization of the existing and alternative dissolution techniques to lay a foundation for Quality by Design (QbD) principles, In Vitro/In Vivo Correlation (IVIVC) and In Vitro/In Vivo Relationship (IVIVR). The dissolution applied on API and on differente formulations types (Immediate release and extended release form) during the different development phases as well as for generic has been explored. Simple and cost effective dissolution methods were shown to be potential surrogate for in vivo performance and serve as well for strong quality control method. The future perspectives and central role of dissolution testing are presented and discussed.