Abstract

STABILITY AND DISSOLUTION BEHAVIOUR OF CYCLODEXTRIN MOLECULAR INCLUSION COMPLEXES OF ARTEMETHER

Zwanden S. Yahaya*, Kenneth C. Ofokansi, Patricia I. Achi and Charles N. Dagogot

ABSTRACT

This study aimed to assess the effect of inclusion complexation of artemether by 2-Hydroxypropyl-β-cyclodextrin on the dissolution and stabilization of the drug against degradation due to exposure to heat. Inclusion complexes of artemether with 2-Hydroxypropyl-β-cyclodextrin of molar ratios 1:1, 1:2 and 1:3 were prepared using the kneading method. Complexes were evaluated for dissolution rate via in-vitro dissolution studies using the Erweka dissolution apparatus at 37 ± 0.5o C in simulated intestinal fluid without pancreatin and simulated gastric fluid without pepsin and compared with a commercial product. Stability tests were carried out on the complexes at room temperature for 10 weeks and at 50o C for 72 h to accelerate the possible degradation of artemether in the presence of 2-Hydroxypropyl-β-cyclodextrin. The complexes exhibited higher and faster dissolution rate than the pure drug and a marketed product. The extent of dissolution enhancement varied with the host-guest molar ratios in the following order 1:3 M > 1:2 M > 1:1 M. However, the differences in dissolution between the pure drug and the inclusion complexes were found to be significant (p < 0.05). In simulated intestinal fluid without pancreatin, the prepared inclusion complexes yielded drug release profiles comparable and even slightly better than a commercial parenteral formulation. Stability data showed no significant differences in physical appearance and drug content over a reasonable period indicating good stability of the formulation. We conclude that inclusion complexation of artemether with 2-Hydroxypropyl-β-cyclodextrin is a promising alternative to enhance the stability and dissolution rate of the drug.

Keywords: Artemether, 2-hydroxypropyl-?-Cyclodextrin, inclusion complex, dissolution, stability.