Effect of Recrystallization Technique on Oral Bioavailability of Olmesartan

Abstract

Olmesartan medoxomil (OLM) is a widely prescribed anti-hypertensive agent with angiotensin II type I receptor
antagonistic activity. OLM belongs to BCS class II having a low and variable oral bioavailability (BA) (29%) and
its absorption is dissolution rate limited. Recrystallization of OLM from different organic solvents improved its
aqueous solubility andtherebyin vitro dissolution properties. In this investigation, oral BA of Olmesartan (OL)
(parent drug molecule of OLM) from recrystallized products of OLM with acetonitrile and methanol (OACN and
OMET respectively) solvents were evaluated in male Wistar rats. Also, a rapid, economical and reliable RPHPLC-PDA method was developed for the estimation of OL in rat plasma samples and validated according to
ICH guidelines. Chromatographic separation was achieved on an Agilent eclipse C18 column (150×4.6mm, 5µ)
with a mobile phase composition of 10mM ammonium acetate - Acetonitrile (62:38%v/v) at a flow rate of 1.2
mL/min. The retention time of OL was found to be 2.3 min and showed good linearity (R2>0.99) in the selected
concentration range of 0.2-1.0µg/mL. A 1.8, 1.6 folds increase in Cmax and a relative BA of 186, 160% were
observed with OACN and OMET respectively, when compared to that of untreated OLM. Thus it can be inferred
that recrystallization can be easily scalable and economical technique for enhancing the pharmaceutical properties
like solubility, dissolution properties and oral BA of poorly water soluble drugs like OLM.