Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach

Mutalik, Srinivas, Anju, Parambil, Manj, Krishnan and Usha, Nayak (2008) Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach. International Journal of Pharmaceutics, 350 1-2: 279-290. doi:10.1016/j.ijpharm.2007.09.006


Author Mutalik, Srinivas
Anju, Parambil
Manj, Krishnan
Usha, Nayak
Title Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
Publication date 2008-02
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2007.09.006
Volume 350
Issue 1-2
Start page 279
End page 290
Total pages 12
Place of publication Netherlands
Publisher Elsevier BV
Language eng
Abstract In this study the significant effect of chitosan on improving the dissolution rate and bioavailability of aceclofenac has been demonstrated by simple solvent change method. Chitosan was precipitated on aceclofenac crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals with different concentrations of chitosan (0.05-0.6%) were characterized in terms of solubility, drug content, particle size, thermal behaviour (differential scanning calorimetry, DSC), X-ray diffraction (XRD), morphology (scanning electron microscopy, SEM), in vitro drug release and stability studies. The in vivo performance was assessed by preclinical pharmacodynamic (analgesic and anti-inflammatory activity) and pharmacokinetic studies. The particle size of the prepared co-crystals was drastically reduced during the formulation process. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from optimized crystal formulation was attributed to the wetting effect of chitosan, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on storage at accelerated conditions. The in vivo studies revealed that the optimized crystal formulation provided a rapid pharmacological response in mice and rats besides exhibiting improved pharmacokinetic parameters in rats.
Keyword Aceclofenac
Chitosan
Crystals
Dissolution
Pharmacodynamics
Pharmacokinetics
Sodium citrate
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Thu, 03 Sep 2009, 10:26:09 EST by Mr Andrew Martlew on behalf of School of Pharmacy