Preparation and characterization of artemether inclusion complexes with hydroxypropyl-β-cyclodextrin

Zwanden Sule Yahaya,Suzane T Allagh,Kenneth C Ofokansi,Pat G Bhatia

doi:10.4314/tjpr.v16i10.7

Abstract

Purpose: To investigate experimentally the inclusion of artemether into the cavity of hydroxypropyl-β-cyclodextrin and examine its effect on the solubility and dissolution rate of the drug.Methods: Inclusion complexes of artemether with hydroxypropyl-β-cyclodextrin of molar ratios 1:1, 1:2 and 1:3 were prepared using the kneading method. Phase solubility analysis and in vitro dissolution studies were utilized in evaluating the influence of inclusion complex formation on the solubility and dissolution rate of the drug. The complexes were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The inclusion complex containing equimolar concentrations of artemether and hydroxypropyl-β-cyclodextrin was then formulated into tablets via direct compression and evaluated for various pharmaceutical characteristics including hardness, friability, absolute drug content and comparative in vitro dissolution profiles with some commercially available brands of artemether.Results: The phase solubility diagram for the formed complexes in water at 37 oC indicated a linear curve soluble complex system (referred to as the AL system), and a stability constant (KC) value of 143 M-1. Evidence consistent with inclusion complex formation was obtained using FT-IR and DSC. The formulated inclusion complex tablets exhibited a higher rate of dissolution than the pure drug and commercial brands, showing 3.9-, 1.8- and 1.6-fold increases, respectively, over a period of 15 min.Conclusion: Inclusion complexation of artemether with hydroxypropyl-β-cyclodextrin is a promising approach to enhance the solubility and dissolution rate of the drug.Keywords: Artemether, 2-Hydroxypropyl-β-cyclodextrin, Dissolution, Solubility enhancement, Inclusion complex

Highlights

All drugs, regardless of their route of administration, should exhibit at least limited aqueous solubility for therapeutic efficiency
Inclusion complex of artemether-cyclodextrin of molar ratio 1:1 was used for the preparation of tablets
The phase solubility diagram gave a straight line with R2 value of 0.9963 and y = 0.0014x + 7E-06

Summary

Introduction

Regardless of their route of administration, should exhibit at least limited aqueous solubility for therapeutic efficiency. Relatively insoluble compounds can exhibit erratic or incomplete absorption, and it might be appropriate to use more soluble salts or chemical derivatives. Molecular complexation is the interaction between “guest” molecules and cyclodextrins (CD) to form reversible inclusion complex which has been shown to be an effective means of increasing the aqueous solubility of hydrophobic compounds [2]. There are three types of natural cyclodextrins – alpha (α), beta (β), and gamma (γ) with six, seven and eight glucopyranose units, respectively. The cyclodextrin cavity dimension, which is important for guest-host interaction, ranges from 0.174 to 0.427 nm for alpha and gamma cyclodextrins respectively [2,3]

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