title: Formulation, optimization, and in vitro-in vivo evaluation of olmesartan medoxomil nanocrystals.
abstract: The aim of the present study is to increase the saturation solubility and oral bioavailability of olmesartan medoxomil (OLM) using nano-sized crystals produced using a combination of antisolvent precipitation and high-shear homogenization. A response surface design comprising 46 runs was used to optimize the OLM nanocrystal formulation. The optimized formulation was produced using a combination of D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) (0.7% w/v), Pluronic F-68® (0.5% w/v), and drug concentration (0.2% w/v) and subjected to 10 and 15 homogenization cycles at 1000 and 1700 bar, respectively. The particle size, polydispersity index (PDI), and zeta potential of optimized formulation were found to be 140 ± 10.34 nm, 0.07 ± 0.016, and -21.43 ± 2.33 mV, respectively. The optimized formulation exhibited irregular morphology as evaluated by scanning electron microscopy and was crystalline as determined by thermal analysis and powder X-ray diffraction studies. OLM nanocrystals showed a marked increase in the saturation solubility as well as rapid dissolution rate in comparison with the pure drug. No significant change in the particle size, PDI, and zeta potential was observed when optimized formulation was stored at room and refrigeration conditions for 3 months. Lastly, in vivo pharmacokinetic studies in Sprague-Dawley rats substantiate the ability of OLM nanocrystal formulation to significantly improve (∼4.6-fold) the oral bioavailability of OLM in comparison with the free drug. This study has established a potential and commercial viable OLM formulation with enhanced saturation solubility and in vivo oral bioavailability.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India. sanyogjain@niper.ac.in.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Patel
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Arora
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India.
authors.forename: Venkata Appa
authors.initials: VA
authors.lastname: Reddy
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S, Nagar, Punjab, 160062, India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D005260:Female; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D000068557:Olmesartan Medoxomil / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D033362:Powder Diffraction; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D013501:Surface-Active Agents; D020442:Poloxamer; D000068557:Olmesartan Medoxomil
keywords: Antisolvent precipitation; High-pressure homogenization; Nanocrystals; Olmesartan medoxomil; Oral bioavailability