Studies on inclusion complex as potential systems for enhancement of oral bioavailability of olmesartan medoxomil

Abstract

Background: Olmesartan medoxomil (OLM), an anti-hypertensive agent administered orally, has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml). Inclusion complexation with cyclodextrins (CD) has been reported to increase the aqueous solubility of various compounds. Aim: The present investigation aimed to enhancing the oral bioavailability of OLM by inclusion complexation with 2-hydroxypropylβ-cyclodextrin (HP-β-CD). Materials and Methods: The inclusion complexes with HP-β-CD were prepared using two different methods, viz., physical mixture and kneading. The prepared complexes were characterized for various parameters such as drug content, aqueous solubility, dissolution study, in vitro diffusion, intestinal permeability and stability study. The formation of the inclusion complex was confirmed by differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. Results: The solubility, dissolution, diffusion rate, and intestinal permeability of the prepared complexes were found to be significantly higher than that of the plain drug. Among the two methods used for formation of inclusion complex, KN method gave higher solubility rates and hence is a better method when compared with PM. Conclusion: The approach seems to be promising in improving the oral bioavailability of OLM.

Host–Guest Interaction Study of Olmesartan Medoxomil with β-Cyclodextrin Derivatives

“…Interactions can also be observed for the physical mixtures, even in the case of physical mixtures prepared without grinding, but only gentle mixing with a spatula, but they are weaker than those in the kneaded products. The interaction between OLM and 2 hydroxypropyl-β-CD even in the physical mixtures was also reported by Thakkar et al [35]. The smaller mass loss in the temperature range of 40-110 • C observed in the case of KP compared to PM and PMG proves a more intense interaction of OLM and RM-β-CD when the kneading method was used, since the driving force for complexation involves the replacement of high-energy water molecule in the host cavity by guest molecules [46].…”

“…Complexation of active pharmaceutical ingredients with CD is one of the valuable strategies used to enhance the solubility of poorly water-soluble drugs, the dissolution rate, and consequently their bioavailability [28,34]. Thakkar et al [35] have investigated the inclusion of OLM in HP-β-CD cavity and reported significantly higher saturation solubility, dissolution rate, and intestinal permeation for OLM/HP-β-CD binary systems.…”

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“…[9,10] The unabsorbed drug may cause gastrointestinal side effects such as abdominal pain, dyspepsia, gastroenteritis, and nausea. [11] In the literature nanoparticles, [12] nanosuspension [10] and complexation with cyclodextrin [11] have been reported to improve solubility of OLM. Therefore, formulation approaches are being explored to enhance dissolution of OLM using poloxamer 407.…”

Integrated Quality by Design Approach for Developing Nanolipidic Drug Delivery Systems of Olmesartan Medoxomil with Enhanced Antihypertensive Action

“…6,7 Several literature reports have demonstrated the application different solubility enhancement technologies for improving biopharmaceutical performance of the drug. [8][9][10][11][12] However, beyond solubility, many other rate-limiting factors tend to affect the oral bioavailability of OMT. Some of them are first-pass effect and terminal metabolism by gut enzymes.…”