title: Refining stability and dissolution rate of amorphous drug formulations.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Copenhagen, Department of Pharmacy , Universitetsparken 2, 2100 Copenhagen , Denmark +45 3533 6032 ; Thomas.rades@sund.ku.dk.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.forename: Petra A
authors.initials: PA
authors.lastname: Priemel
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
authors.forename: Line Hagner
authors.initials: LH
authors.lastname: Nielsen
authors.forename: Riikka
authors.initials: R
authors.lastname: Laitinen
authors.forename: Anette
authors.initials: A
authors.lastname: Mullertz
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D016503:Drug Delivery Systems; D004355:Drug Stability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D014867:Water
keywords: amorphous; co-amorphous systems; dissolution enhancement; in situ; microcontainers; polymers; solid dispersions; stability; surface crystallisation