Grohganz, Holger6; Priemel, Petra A4; Löbmann, Korbinian6; Nielsen, Line Hagner7; Laitinen, Riikka4; Mullertz, Anette6; Van den Mooter, Guy4; Rades, Thomas6
1 Pharmaceutical Technology and Engineering, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet3 IKVH Fysiologi og ernæring samt pelsdyrfarmen, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet6 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet7 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet
Introduction: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its amorphous counterpart is often seen as a potential solution to increase the solubility. However, amorphous systems are physically unstable. Therefore, pharmaceutical formulations scientists need to find ways to stabilise amorphous forms. Areas covered: The use of polymer-based solid dispersions is the most established technique for the stabilisation of amorphous forms, and this review will initially focus on new developments in this field. Additionally, newly discovered formulation approaches will be investigated, including approaches based on the physical restriction of crystallisation and crystal growth and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. Expert opinion: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed.
Expert Opinion on Drug Delivery, 2014, Vol 11, Issue 6, p. 977-89