EZETIMIBE NANOSTRUCTURED LIPID CARRIERS (NLCs): A NEW TECHNIQUE TO OVERCOME THE LIMITATIONS OF ORAL ADMINISTRATION

RASHAD M. KAOUD; EMAN J. HEIKAL; SHADEED GAD

doi:10.22159/ijap.2022v14i3.44072

Authors

RASHAD M. KAOUD Pharmacy Department, Ashur University College, PO Box 10047, Baghdad, Iraq https://orcid.org/0000-0001-8537-7066
EMAN J. HEIKAL Faculty of Pharmacy, The University of Mashreq, Baghdad, Iraq
SHADEED GAD Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt

DOI:

https://doi.org/10.22159/ijap.2022v14i3.44072

Keywords:

Ezetimibe (EMB), Nanostructured lipid carriers (NLCs), Bioavailability and Oral delivery

Abstract

Objective: Ezetimibe (EMB) is a commonly used lipid-lowering medication that lowers cholesterol and triglycerides. Because of its lower water solubility and hepatic metabolism, it necessitates the formulation of drug delivery systems that are capable of improving solubility and avoiding hepatic effect.

Methods: Ezetimibe nanostructured lipid carriers (EMB-NLCs) were formulated and examined. They were formulated through emulsification with a high homogenization speed and ultrasonication (The method and evaluation parameters have been mentioned under method section in Formulation of EMB-NLCs paragraph).

Results: The formulated NLCs have exhibited particle size (P. S.) between 163.6±7.20 and 866.66±18.65 nm and the zeta potential (Z. P.) values have ranged between-24±1.25 and-35±0.25 mV. Besides, they exhibited higher EE% than 77 percent and the drug encapsulated in lipid matrix was in amorphous state. Pharmacokinetics of optimized formula (F1; composed of 2% w/w Gelucire^® 43/01, 8% w/w Miglyol^® 812 N, 0.5% w/w lecithin and 2% w/w Poloxmer^® 188) have exhibited 2.63-and 2.33-fold increase in oral bioavailability in comparison with EMB suspension and marketing product (Ezetrol^® 10 mg tablet), respectively.

Conclusion: These studies have demonstrated that, NLCs are superior for enhancing in vivo behavior and oral bioavailability of EMB.

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References

Gupta R. Burden of coronary heart disease in India. Indian Heart J. 2005;57(6):632-8. PMID 16521628.

Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell. 2001;104(4):503-16. doi: 10.1016/s0092-8674(01)00238-0, PMID 11239408.

Hoffmann U, Massaro JM, D’Agostino Sr RB, Kathiresan S, Fox CS, O’Donnell CJ. Cardiovascular event prediction and risk reclassification by coronary, aortic, and valvular calcification in the framingham heart study. J Am Heart Assoc. 2016;5(2):e003144. doi: 10.1161/JAHA.115.003144, PMID 26903006.

Narushima K, Takada T, Yamanashi Y, Suzuki H. Niemann-Pick C1-like 1 mediates α-tocopherol transport. Mol Pharmacol. 2008;74(1):42-9. doi: 10.1124/mol.107.043034, PMID 18403720.

Suchy D, Labuzek K, Stadnicki A, Okopien B. Ezetimibe-a new approach in hypercholesterolemia management. Pharmacol Rep. 2011;63(6):1335-48. doi: 10.1016/s1734-1140(11)70698-3, PMID 22358082.

Tessier N, Moawad F, Amri N, Brambilla D, Martel C. Focus on the lymphatic route to optimize drug delivery in cardiovascular medicine. Pharmaceutics. 2021;13(8):1200. doi: 10.3390/pharmaceutics13081200, PMID 34452161.

O’Dwyer PJ, Box KJ, Koehl NJ, Bennett-Lenane H, Reppas C, Holm R, Kuentz M, Griffin BT. Novel biphasic lipolysis method to predict in vivo performance of lipid-based formulations. Mol Pharm. 2020;17(9):3342-52. doi: 10.1021/ acs.molpharmaceut.0c00427, PMID 32787274.

Koehl NJ, Henze LJ, Bennett Lenane H, Faisal W, Price DJ, Holm R, Kuentz M, Griffin BT. In silico, in vitro, and in vivo evaluation of precipitation inhibitors in supersaturated lipid-based formulations of venetoclax. Mol Pharm. 2021;18(6):2174-88. doi: 10.1021/acs.molpharmaceut.0c00645, PMID 33890794.

Kharwade RS, Mahajan NM. Formulation and evaluation of nanostructured lipid carriers based anti-inflammatory gel for topical drug delivery system. Asian J Pharm Clin Res. 2019;12:286-91.

Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: a review. Pharmaceutics. 2020;12(3):288. doi: 10.3390/pharmaceutics12030288, PMID 32210127.

Elmowafy M, Ibrahim HM, Ahmed MA, Shalaby K, Salama A, Hefesha H. Atorvastatin-loaded nanostructured lipid carriers (NLCs): strategy to overcome oral delivery drawbacks. Drug Deliv. 2017;24(1):932-41. doi: 10.1080/10717544.2017.1337823, PMID 28617150.

Agrawal YO, Mahajan UB, Mahajan HS, Ojha S. Methotrexate-loaded nanostructured lipid carrier gel alleviates imiquimod-induced psoriasis by moderating inflammation: formulation, optimization, characterization, In vitro and in vivo studies. Int J Nanomedicine. 2020;15:4763-78. doi: 10.2147/IJN.S247007, PMID 32753865.

Setyawati DR, Surini S, Mardliyati E. Optimization of luteolin-loaded transfersome using response surface methodology. Int J App Pharm. 2017;9:107-11. doi: 10.22159/ijap.2017.v9s1.64_71.

Rajeswari S, Swapna V. Microsponges as a neoteric cornucopia for drug delivery systems. Int J Curr Pharm Sci. 2019;11:4-12. doi: 10.22159/ijcpr.2019v11i3.34099.

Nasr AM, Qushawy MK, Elkhoudary MM, Gawish AY, Elhady SS, Swidan SA. Quality by design for the development and analysis of enhanced in-situ forming vesicles for the improvement of the bioavailability of fexofenadine HCl in vitro and in vivo. Pharmaceutics. 2020;12(5):409. doi: 10.3390/pharmaceutics12050409, PMID 32365695.

Sinko PJ. Walter kluer, pharm symposium pharmaceutical sciences: physical chemical and biopharmaceutical principles in the pharmaceutical sciences; 2011. p. 472-7.

Kalam MA, Humayun M, Parvez N, Yadav S, Garg A, Amin S. Release kinetics of modified pharmaceutical dosage forms: a review. Cont J Pharm Sci. 2007;1:30-5.

Nasr M, Mansour S, Mortada ND, Elshamy AA. Vesicular aceclofenac systems: a comparative study between liposomes and niosomes. J Microencapsul. 2008;25(7):499-512. doi: 10.1080/02652040802055411, PMID 18608811.

Jesus JA, Sousa IMO, da Silva TNF, Ferreira AF, Laurenti MD, Antonangelo L, Faria CS, da Costa PC, de Carvalho Ferreira D, Passero LFD. Preclinical assessment of ursolic acid loaded into nanostructured lipid carriers in experimental visceral leishmaniasis. Pharmaceutics. 2021;13(6):908. doi: 10.3390/pharmaceutics13060908, PMID 34205283.

Kassem AM, Ibrahim HM, Samy AM. Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation. J Microencapsul. 2017;34(3):319-33. doi: 10.1080/02652048.2017.1328464, PMID 28481663.

Fangueiro JF, Gonzalez Mira E, Martins Lopes P, Egea MA, Garcia ML, Souto SB, Souto EB. A novel lipid nanocarrier for insulin delivery: production, characterization and toxicity testing. Pharm Dev Technol. 2013;18(3):545-9. doi: 10.3109/10837450.2011.591804, PMID 21711084.

Luan J, Zhang D, Hao L, Li C, Qi L, Guo H, Liu X, Zhang Q. Design and characterization of amoitone b-loaded nanostructured lipid carriers for controlled drug release. Drug Deliv. 2013;20(8):324-30. doi: 10.3109/10717544.2013.835007, PMID 24032657.

Kaul S, Gulati N, Verma D, Mukherjee S, Nagaich U. Role of nanotechnology in cosmeceuticals: a review of recent advances. J Pharm (Cairo). 2018;2018:3420204. doi: 10.1155/2018/3420204, PMID 29785318.

Yang Y, Zheng N, Wang X, Ivone R, Shan W, Shen J. Rapid preparation of spherical granules via the melt centrifugal atomization technique. Pharmaceutics. 2019;11(5):198. doi: 10.3390/pharmaceutics11050198, PMID 31052257.

Che J, Okeke CI, Hu ZB, Xu J. DSPE-PEG: a distinctive component in drug delivery system. Curr Pharm Des. 2015;21(12):1598-605. doi: 10.2174/1381612821666150115144003, PMID 25594410.

Iqbal MA S, Mustafa G, Kumar M, Baboota S, Sahni JK. Formulation, optimization and evaluation of nanostructured lipid carrier system of acyclovir for topical delivery. J Bionanoscience. 2014;8:235–47.

Murthy A, Ravi PR, Kathuria H, Malekar S. Oral bioavailability enhancement of raloxifene with nanostructured lipid carriers. Nanomaterials (Basel). 2020;10(6):1085. doi: 10.3390/nano10061085, PMID 32486508.

Seyam S, Nordin NA, Alfatama M. Recent progress of chitosan and chitosan derivatives-based nanoparticles: pharmaceutical perspectives of oral insulin delivery. Pharmaceuticals (Basel). 2020;13(10):307. doi: 10.3390/ph13100307, PMID 33066443.