Investigation on Dissolution Pattern and Mathematical Modeling of Drug Release of UDCA by Complextaion with b-Cyclodextrin-Choline Dichloride Coprecipitate

Kamal Dua,Kavita Pabreja

doi:10.4172/2167-0889.1000101

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 Ursodeoxycholic acid (UDCA) from molecular inclusion complexes. The molecular inclusion complexes of UDCA with β-CD coprecipitated with CDC were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures and cyclodextrin inclusion complexes (UDCA-β-CD- CDC) were carried out. Molecular inclusion complexes of Ursodeoxycholic acid with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH 7.4. Inclusion complexes with 1:2M ratio showed maximum dissolution rate in comparison to other ratios. FT-IR spectroscopy and differential scanning calorimetry studies indicated no interaction between UDCA 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 followed by Higuchi release model. In conclusion, dissolution of Ursodeoxycholic acid can be enhanced by using the β-CD-CDC coprecipitate as a host st molecolec.

Highlights

Up to 40 percent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds [1]
Low coefficient of variance (CV) values (< 1.0 %) in percentage yield indicates the reproducibility of the technique employed for the preparation of molecular inclusion complexes
The numerous diffraction peaks with high intensities in ursodeoxycholic acid its existence in a highly crystalline state, while in β-cyclodextrin-CDC complexes, X-ray diffraction (X-RD) patterns showed a broad diffraction band with markedly reduced intensity.The results indicate the existence of Ursodeoxycholic acid (UDCA) in amorphous state and showing enhanced aqueous solubility

Summary

Introduction

Up to 40 percent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds [1]. The dissolution characteristics of poorly soluble drugs can be enhanced by several methods [5,6,7]. Cyclodextrin and their derivatives play an important role in formulation development due to their effect on solubility, dissolution rate, chemical stability and absorption of drugs. Ursodeoxycholic acid (UDCA) (Figure 1) is a white, odorless, crystalline powder with a bitter taste. The possibility to increase the complexing ability of β-CD by their prior coprecipitation with molecules like choline dichloride able to increase the aqueous solubility of lipophilic drugs seemed to represent a further approach to the utilization of β-CD as aqueous solubility and attempt has been made to prepare inclusion complexes of Ursodeoxycholic acid with coprecipitated β-cyclodextrin (β-CD) with an aim to improve its extent and rate of dissolution

Material and Methods

Findings

Result and Discussion

Conclusion