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Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation.
Drug Deliv 2016; 23(2):395-404DD

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+Show Affiliations

a Department of Nanotechnology , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Andra Pradesh , India.a Department of Nanotechnology , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , Andra Pradesh , India.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24865287

Citation

Dudhipala, Narendar, and Kishan Veerabrahma. "Candesartan Cilexetil Loaded Solid Lipid Nanoparticles for Oral Delivery: Characterization, Pharmacokinetic and Pharmacodynamic Evaluation." Drug Delivery, vol. 23, no. 2, 2016, pp. 395-404.
Dudhipala N, Veerabrahma K. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Deliv. 2016;23(2):395-404.
Dudhipala, N., & Veerabrahma, K. (2016). Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Delivery, 23(2), pp. 395-404. doi:10.3109/10717544.2014.914986.
Dudhipala N, Veerabrahma K. Candesartan Cilexetil Loaded Solid Lipid Nanoparticles for Oral Delivery: Characterization, Pharmacokinetic and Pharmacodynamic Evaluation. Drug Deliv. 2016;23(2):395-404. PubMed PMID: 24865287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. AU - Dudhipala,Narendar, AU - Veerabrahma,Kishan, Y1 - 2014/05/28/ PY - 2014/5/29/entrez PY - 2014/5/29/pubmed PY - 2016/12/15/medline KW - Candesartan cilexetil KW - pharmacodynamics KW - pharmacokinetics KW - solid lipid nanoparticles KW - triglycerides SP - 395 EP - 404 JF - Drug delivery JO - Drug Deliv VL - 23 IS - 2 N2 - 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. SN - 1521-0464 UR - https://www.unboundmedicine.com/medline/citation/24865287/Candesartan_cilexetil_loaded_solid_lipid_nanoparticles_for_oral_delivery:_characterization_pharmacokinetic_and_pharmacodynamic_evaluation_ L2 - http://www.tandfonline.com/doi/full/10.3109/10717544.2014.914986 DB - PRIME DP - Unbound Medicine ER -