Enhancement of Dissolution Behavior of Aceclofenac by Complexation with β-Cyclodextrin-Choline Dichloride Coprecipitate

Abstract

The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. The molecular inclusion complexes of AF with β-CD coprecipitated with CDC in 1:1 and 1:2 M ratio were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes (AF-β-CD-CDC) were carried out. Molecular inclusion complexes of aceclofenac with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH, 7.4. Inclusion complexes with 1:2 M ratio showed maximum dissolution rate in comparison to other ratios. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics (R ² = 0.9354 and 0.9268 in 0.1 N HCl and phosphate buffer, respectively) followed by Higuchi release model (R ² = 0.9029 and 0.9578 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, dissolution of aceclofenac can be enhanced by using the β-CD-CDC coprecipitate as a host molecule.

Keywords:

• Aceclofenac
• β-CD
• CDC
• complexes
• solubility

Notes

AF: aceclofenac; CDC: choline dichloride; β-CD: β-cyclodextrin; M: molar. Values in parenthesis indicates the standard deviation (n = 3) and values given in the parenthesis marked with * indicates theoretical values of drug content.

AF: aceclofenac; CDC: choline dichloride; β-CD: β-cyclodextrin; M: molar. Values in parenthesis indicates the standard deviation (n = 3).

AF: aceclofenac; β-CD: Hydroxypropyl β-cyclodextrin; CDC: choline dichloride; M: molar; PM: physical mixture. Mean and standard deviation (in parenthesis), n = 6.

AF: aceclofenac; β-CD: β-cyclodextrin; CDC: choline dichloride; M: molar.

AF: aceclofenac; β-CD: β-cyclodextrin; CDC: choline dichloride; M: molar.