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AAPS PharmSciTech

, Volume 18, Issue 8, pp 2841–2853 | Cite as

Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance

  • Michael M. Puppolo
  • Justin R. Hughey
  • Traciann Dillon
  • David Storey
  • Susan Jansen-Varnum
Review Article

Abstract

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.

KEY WORDS

free drug bioavailability membrane permeation dissolution amorphous solid dispersion poorly water soluble 

Notes

Acknowledgements

The authors wish to gratefully acknowledge the financial support of Hovione LLC. The authors would also like to thank Dr. Bruce Weber for his critical review of this manuscript.

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Michael M. Puppolo
    • 1
    • 2
  • Justin R. Hughey
    • 3
  • Traciann Dillon
    • 1
  • David Storey
    • 1
  • Susan Jansen-Varnum
    • 2
  1. 1.Hovione LLCEast WindsorUSA
  2. 2.Department of ChemistryTemple UniversityPhiladelphiaUSA
  3. 3.Banner Life SciencesHigh PointUSA

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