title: Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation.
abstract: Candesartan cilexetil (CC) is used in the treatment of hypertension and heart failure. It has poor aqueous solubility and low oral bioavailability. In this work, CC loaded solid lipid nanoparticles (CC-SLNs) were developed to improve the oral bioavailability. Components of the SLNs include either of trimyristin/tripalmitin/tristearin, and surfactants (Poloxamer 188 and egg lecithin E80). The CC loaded nanoparticles were prepared by hot homogenization followed by ultrasonication method. The physicochemical properties, morphology of CC-SLNs were characterized, the pharmacokinetic and pharmacodynamic behaviour of CC-SLNs were evaluated in rats. Stable CC-SLNs having a mean particle size of 180-220 nm with entrapment efficiency varying in between 91-96% were developed. The physical stability of optimized formulation was studied at refrigerated and room temperature for 3 months. Further, freeze drying was tried for improving the physical stability. DSC and XRD analyses indicated that the drug incorporated into SLN was in amorphous form but not in crystalline state. The SLN-morphology was found to be nearly spherical by electron microscopic studies. Pharmacokinetic results indicated that the oral bioavailability of CC was improved over 2.75-fold after incorporation into SLNs. Pharmacodynamic study of SLNs in hypertensive rats showed a decrease in systolic blood pressure for 48 h, while suspension showed a decrease in systolic blood pressure for only 2 h. Taken together, these effects are due to enhanced bioavailability coupled with sustained action of CC in SLN formulation. Thus, the results conclusively demonstrated the role of CC-SLNs for a significant enhancement in oral bioavailability along with improved pharmacodynamic effect.
authors.affiliation: a Department of Nanotechnology , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Andra Pradesh , India.
authors.forename: Narendar
authors.initials: N
authors.lastname: Dudhipala
authors.affiliation: a Department of Nanotechnology , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Andra Pradesh , India.
authors.forename: Kishan
authors.initials: K
authors.lastname: Veerabrahma
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects*; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005632:Fructose; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D033362:Powder Diffraction; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013777:Tetrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014465:Ultrasonics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D013777:Tetrazoles; D005632:Fructose; C077793:candesartan cilexetil
keywords: Candesartan cilexetil; pharmacodynamics; pharmacokinetics; solid lipid nanoparticles; triglycerides