EVALUATION OF THE DISSOLUTION AND OTHER CHARACTERISTICS OF CYCLODEXTRIN MOLECULAR INCLUSION COMPLEXES OF ARTEMETHER

ABSTRACT

The present study aimed to improve the dissolution rate, solubility and ultimately, bioavailability of poorly soluble artemether, an antimalarial drug, through inclusion complex formation with hydroxypropyl-β-cyclodextrin.

The solid complexes of artemether and hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared at a molar ratio of 1:1, 1:2 and 1:3 by kneading method. The effect of HP-β-CD on the aqueous solubility and dissolution rate of artemether was investigated through phase solubility analysis and in-vitro dissolution studies. The formation of inclusion complexes between artemether and HP-β-CD was confirmed by Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). The inclusion complex containing artemether: HP-β-CD (1:1 M) was further formulated into tablets by direct compression. The prepared tablets were evaluated for various pharmaceutical characteristics; crushing strength, friability, drug content and in-vitro dissolution profiles.

Phase solubility diagram for the complex formation between artemether and HP-β-CD in water at 37 oC indicated the AL type, with an apparent stability constant KC found to be 143 M-1. FT-IR spectroscopy and DSC confirmed the true inclusion of artemether into the cyclodextrin cavity. Prepared inclusion complex tablets exhibited higher and faster dissolution rate than the pure drug and marketed products. It was observed that the inclusion complex tablet  showed a 3.9-fold  increase in the amount  of drug released in 15 min

compared to the plain drug, 1.8-fold increase compared to the marketed brand – Lumartem®

and 1.6-fold increase compared to Coartem®. At 120 min, none of the marketed tablets released up to 90 % of the drug, but the inclusion complex tablet achieved 90 % drug release

in 31 min. The results of stability studies revealed no change in physical appearance and drug content over a reasonable period (ten weeks for short term stability test and 72 h for accelerated stability test), thus indicating that the formulation was stable. The result of the study shows that complexation of artemether by cyclodextrins is a good approach to enhance the solubility and dissolution rate of the drug.