title: Advancing in-vitro drug precipitation testing: new process monitoring tools and a kinetic nucleation and growth model.
abstract: OBJECTIVE
  Poorly soluble weak bases often precipitate during intestinal passage, potentially leading to incomplete drug absorption. The underlying in-vivo and in-vitro drug precipitation mechanisms are not well understood. Thus, new analytical tools and a kinetic nucleation and growth model were introduced to in-vitro drug precipitation testing in biorelevant media.
  
  
  METHODS
  A drug precipitation test was used to simulate the transfer from the stomach to the intestine. Changes in the acceptor vessel were monitored using online dynamic image analysis and inline Raman spectroscopy. The concentration profiles of the model drug dipyridamole were analysed by high-performance liquid chromatography and the resulting data were fitted with a set of differential equations.
  
  
  RESULTS
  The dynamic image analysis revealed a complex structure of the precipitated dipyridamole particles, which were described as star-like crystals or aggregates of elongated primary particles. Raman spectroscopy allowed the precipitation over time to be monitored. Using the kinetic nucleation and growth model to describe this process demonstrated perfect agreement with the experimental data.
  
  
  CONCLUSIONS
  The analytical methods and the kinetic model provided new insights into biorelevant drug precipitation and could in the future support formulation development.
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Yvonne E
authors.initials: YE
authors.lastname: Arnold
authors.forename: Georgios
authors.initials: G
authors.lastname: Imanidis
authors.forename: Martin T
authors.initials: MT
authors.lastname: Kuentz
mesh_terms: D011232:Chemical Precipitation; D004176:Dipyridamole / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000737:chemistry; D008954:Models, Biological; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods; D013270:Stomach / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole