Development of bisphosphonates controlled delivery systems for bone implantation: influence of the formulation and process used on in vitro release

  • A. Billon-Chabaud
  • A. Gouyette
  • C. Merle
  • J. M. Bouler


The present study investigates the development of controlled drug delivery devices by association of bisphosphonates (BPs) with calcium-deficient apatite (CDA) to obtain a prolonged drug delivery. In a first part, we studied the microencapsulation of methylene bisphosphonic acid, our model of BPs, in biodegradable PLGA by the double emulsion (w/o/w) solvent evaporation/extraction process. Secondly, we associated BPs, either in a free form or microencapsulated, with calcium phosphate biomaterials. The association of free BPs with CDA was performed by isostatic compression at 80 MPa and we tested the interest of adding a binder, HPMC, in the formulation to reinforce the association. In parallel, microparticles were associated with calcium-deficient apatite, either by simple mixture or by isostatic compression. To compare the different formulations, in vitro dissolution studies were performed. All the formulations tested appear to be efficient to produce BPs loaded biomaterials able to deliver the drug slowly and at a constant rate. The slowest release rate (2.7% in 14 days) was obtained with the blend of microencapsulated BPs with CDA.


Drug Release Bisphosphonates Encapsulation Efficiency Dissolution Study DCPD 
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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • A. Billon-Chabaud
    • 1
    • 2
  • A. Gouyette
    • 1
    • 2
  • C. Merle
    • 1
    • 2
  • J. M. Bouler
    • 1
  1. 1.INSERM, U 791, Laboratoire d’ingénierie ostéo-articulaire et dentaire, LIOADUniversité de NantesNantesFrance
  2. 2.Laboratoire de Pharmacie Galénique, UFR de Sciences Pharmaceutiques et BiologiquesUniversité de Nantes, Nantes Atlantique UniversitésNantesFrance

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