Solubilized formulation of olmesartan medoxomil for enhancing oral bioavailability.
Olmesartan medoxomil (OLM) is an antihypertensive angiotensin II receptor blocker. OLM has a low bioavailability (BA), approximately 26% in humans, due to its low water solubility and efflux by drug resistance pumps in the gastrointestinal tract. Self-microemulsifying drug delivery system (SMEDDS), which is easily emulsified in aqueous media under gentle agitation and digestive motility, was formulated to increase the oral BA of OLM. Among the surfactants and oils studied, Capryol 90, Tween 20, and Tetraglycol were chosen and combined at a volume ratio of 1:6:3 on the basis of equilibrium solubility and phase diagram experiments. The mean droplet size of SMEDDS was 15 nm. In an oral absorption study in rats, SMEDDS formulation brought faster absorption compared to suspension, showing a T(max) value of 0.2 hr. The C(max) and AUC values of SMEDDS formulation were significantly higher than those of suspension, revealing a relative BA of about 170%. Our study demonstrated the potential usefulness of SMEDDS for the oral delivery of poorly absorbable compounds, including OLM.
Lee
Bong Sang
BS
Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Kang
Myung Joo
MJ
Choi
Woo Sik
WS
Choi
Yoon Bae
YB
Kim
Hyung Soo
HS
Lee
Sang Kil
SK
Lee
Jaehwi
J
Choi
Young Wook
YW
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009821:Oils / Q000737:chemistry; D000068557:Olmesartan Medoxomil; D010316:Particle Size; D044367:Phase Transition; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013777:Tetrazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics
D047228:Angiotensin II Type 1 Receptor Blockers; D004655:Emulsions; D005079:Excipients; D007093:Imidazoles; D009821:Oils; D013501:Surface-Active Agents; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil