title: A Novel Approach for Analyzing the Dissolution Mechanism of Solid Dispersions.
abstract: OBJECTIVE
  To analyze the dissolution mechanism of solid dispersions of poorly water-soluble active pharmaceutical ingredients (APIs), to predict the dissolution profiles of the APIs and to find appropriate ways to improve their dissolution rate.
  
  
  METHODS
  The dissolution profiles of indomethacin and naproxen from solid dispersions in PVP K25 were measured in vitro using a rotating-disk system (USP II). A chemical-potential-gradient model combined with the thermodynamic model PC-SAFT was developed to investigate the dissolution mechanism of indomethacin and naproxen from their solid dispersions at different conditions and to predict the dissolution profiles of these APIs.
  
  
  RESULTS
  The results show that the dissolution of the investigated solid dispersions is controlled by dissolution of both, API and PVP K25 as they codissolve according to the initial API loading. Moreover, the dissolution of indomethacin and naproxen was improved by decreasing the API loading in polymer (leading to amorphous solid dispersions) and increasing stirring speed, temperature and pH of the dissolution medium. The dissolution of indomethacin and naproxen from their amorphous solid dispersions is mainly controlled by the surface reaction, which implies that indomethacin and naproxen dissolution can be effectively improved by formulation design and by improving their solvation performance.
  
  
  CONCLUSIONS
  The chemical-potential-gradient model combined with PC-SAFT can be used to analyze the dissolution mechanism of solid dispersions and to describe and predict the dissolution profiles of API as function of stirring speed, temperature and pH value of the medium. This work helps to find appropriate ways to improve the dissolution rate of poorly-soluble APIs.
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, 44227, Dortmund, Germany, Yuanhui.Ji@bci.tu-dortmund.de.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Ji
authors.forename: Raphael
authors.initials: R
authors.lastname: Paus
authors.forename: Anke
authors.initials: A
authors.lastname: Prudic
authors.forename: Christian
authors.initials: C
authors.lastname: Lübbert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sadowski
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013696:Temperature; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D009288:Naproxen; D011205:Povidone; D007213:Indomethacin