Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet
Yogeeta O. Agrawal,
Umesh B. Mahajan,
Vinit V. Agnihotri,
Mayur S. Nilange,
Hitendra S. Mahajan,
Charu Sharma,
Shreesh Ojha,
Chandragouda R. Patil,
Sameer N. Goyal
Affiliations
Yogeeta O. Agrawal
Department of Pharmaceutics and Quality assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Umesh B. Mahajan
Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Vinit V. Agnihotri
Department of Pharmaceutics and Quality assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Mayur S. Nilange
Department of Pharmaceutics and Quality assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Hitendra S. Mahajan
Department of Pharmaceutics and Quality assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Charu Sharma
Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates
Shreesh Ojha
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates
Chandragouda R. Patil
Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Sameer N. Goyal
Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India
Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of −28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.
