Determination of Inclusion Complex Formation of Metronidazole with 2-Hydroxypropyl-β-Cyclodextrin by HPLC Method

Metronidazole is a nitroimidazole class antibiotic used to treat infections caused by bacteria, protozoa, and parasites. The low solubility of the active pharmaceutical ingredient is the major obstacle to the development and large-scale production of oral solid dosage forms due to its adverse effect on drug absorption and bioavailability. In this study, inclusion complex formation was carried out with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and stability of metronidazole, which has a lipophilic structure and low water solubility. The influence of 2-hydroxypropyl-β-cyclodextrin on the metronidazole solubility was evaluated in respect of the phase solubility method. The complexation of metronidazole with 2-hydroxypropyl-β-cyclodextrin was proven by high performance liquid chromatography method. Liquid chromatographic determination was carried out on a Kinetex Core-Shell C8 (Phenomenex, 150 x 4.6 mm I.D., 2.6 μm) column at 25oC. The acetonitrile-water binary mixture containing 30% (v/v) acetonitrile was used as a mobile phase. As a result, the stoichiometry of the complex was 1:1 and the stability constant of the complex was determined by the high performance liquid chromatography method.