AAPS PharmSciTech

, Volume 14, Issue 1, pp 301–311 | Cite as

Cyclodextrin-Crosslinked Poly(Acrylic Acid): Adhesion and Controlled Release of Diflunisal and Fluconazole from Solid Dosage Forms

  • Marguerite J. Kutyła
  • Michael W. Boehm
  • Jason R. Stokes
  • P. Nicholas Shaw
  • Nigel M. Davies
  • Ross P. McGeary
  • Jonathan Tuke
  • Benjamin P. Ross
Research Article


The controlled release of diflunisal and fluconazole from tablets made of novel polymers, poly(acrylic acid) (PAA) crosslinked with either β-cyclodextrin (βCD) or hydroxypropyl-βCD (HPβCD), was investigated and Carbopol 934P (Carbopol) was used as a highly crosslinked PAA for comparison. Diflunisal strongly associates with βCD-PAA and HPβCD-PAA polymers (K a of 486 and 6,055 M−1 respectively); thus, it was physically mixed into the conjugates and also precomplexed to identify whether decomplexation has any influence on release kinetics. Fluconazole has poor complexing ability (K a of 34 M−1 with HPβCD-PAA); thus, it was only tested as a physical mixture. Swelling and adhesion studies were conducted on all tablet combinations and adhesivity of the CD-PAA polymer tablets was maintained. Diflunisal release was much slower from HPβCD-PAA tablets than from βCD-PAA, suggesting that a higher degree of complexation retards release. The precomplexed diflunisal release was also slower than the physically mixed diflunisal of the corresponding conjugate. The release closely followed zero-order kinetics for HPβCD-PAA, but was more sigmoidal for βCD-PAA and especially Carbopol. Conversely, poorly associating fluconazole released in almost exactly the same way across both polymers and Carbopol, indicating that the release kinetics of poorly associating drugs are not influenced by the presence of cyclodextrins. In view of the varying profiles and release rates shown with diflunisal for the different polymers, the fluconazole data support the concept that adequate complexation can indeed modulate the release kinetics of drugs.

Key words

controlled release cyclodextrin diflunisal fluconazole poly(acrylic acid) 



Mr. Ron West of the School of Pharmacy is thanked for assistance with tablet manufacturing. We also thank Dr. Geraldine Elliot for helpful discussions. Financial support from the School of Pharmacy is gratefully acknowledged.

Supplementary material

12249_2012_9903_MOESM1_ESM.docx (134 kb)
ESM 1 (DOCX 134 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Marguerite J. Kutyła
    • 1
  • Michael W. Boehm
    • 2
  • Jason R. Stokes
    • 2
  • P. Nicholas Shaw
    • 1
  • Nigel M. Davies
    • 1
  • Ross P. McGeary
    • 1
    • 3
  • Jonathan Tuke
    • 4
  • Benjamin P. Ross
    • 1
  1. 1.School of PharmacyThe University of QueenslandBrisbaneAustralia
  2. 2.School of Chemical EngineeringThe University of QueenslandBrisbaneAustralia
  3. 3.School of Chemistry and Molecular BiosciencesThe University of QueenslandBrisbaneAustralia
  4. 4.School of Mathematical SciencesUniversity of AdelaideAdelaideAustralia

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