Refining stability and dissolution rate of amorphous drug formulations

Holger Grohganz, Petra A. Priemel, Korbinian Lobmann, Line Hagner Nielsen, Riikka Laitinen, Anette Mullertz, Van den Mooter Guy, Thomas Rades

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalExpert Opinion on Drug Delivery
Volume11
Issue number6
Pages (from-to)977-989
Number of pages13
ISSN1742-5247
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • amorphous drug formulation
  • physical restriction
  • polymer
  • polymer-based solid dispersion
  • 10511, Biophysics - Bioengineering
  • 12512, Pathology - Therapy
  • 22002, Pharmacology - General
  • Pharmacology
  • amorphous drug delivery system drug delivery device
  • Biomaterials
  • Pharmaceuticals
  • PHARMACOLOGY
  • WATER-SOLUBLE DRUGS
  • IMPROVED PHYSICAL STABILITY
  • SOLID DISPERSION-SYSTEMS
  • HOT STAGE EXTRUSION
  • IN-VITRO
  • MELT EXTRUSION
  • SURFACE CRYSTALLIZATION
  • PHYSICOCHEMICAL PROPERTIES
  • TEMPORARY PLASTICIZER
  • PHARMACEUTICAL SOLIDS
  • amorphous
  • co-amorphous systems
  • dissolution enhancement
  • in situ
  • microcontainers
  • polymers
  • solid dispersions
  • stability
  • surface crystallisation

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