Generic placeholder image

Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment

Author(s): Shweta Agarwal*, S.L. HariKumar, Poonam Negi, Navneet Upadhyay and Rajeev Garg

Volume 18, Issue 2, 2021

Published on: 28 July, 2020

Page: [184 - 198] Pages: 15

DOI: 10.2174/1567201817999200728135119

Price: $65


Aims: The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC) of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability.

Background: QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in bioavailability would result in minimization of side effects.

Objective: The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential lymphatic uptake.

Methods: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables during optimization by Central Composite Design.

Results: The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of - 19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical, smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cycloheximide untreated rats’ group of QF-NLC by 2.43 times as compared to cycloheximide treated group, confirmed lymphatic absorption of QF- NLC.

Conclusion: The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.

Keywords: Quetiapine fumarate, nanostructured lipid carrier, phospholipon90G, pharmacokinetic, bioavailability, NLC.

Graphical Abstract
The World Health Report 2001: mental disorders affect one in four people. 2001. [Accessed on 27thJan, 20]
Lean, M.E.J.; Pajonk, F.G. Patients on atypical antipsychotic drugs: Another high-risk group for type 2 diabetes. Diabetes Care, 2003, 26(5), 1597-1605.
[] [PMID: 12716824]
Farah, A. Atypicality of atypical antipsychotics. Prim. Care Companion J. Clin. Psychiatry, 2005, 7(6), 268-274.
[] [PMID: 16498489]
DeVane, C.L.; Nemeroff, C.B. Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clin. Pharmacokinet., 2001, 40(7), 509-522.
[] [PMID: 11510628]
Narala, A.; Veerabrahma, K. Preparation, Characterization and evaluation of quetiapine fumarate solid lipid nanoparticles to improve the oral bioavailability. J. Pharm. (Cairo), 2013, 2013, 265741-265748.
[] [PMID: 26555970]
Gareri, P.; Segura-García, C.; Manfredi, V.G.; Bruni, A.; Ciambrone, P.; Cerminara, G.; De Sarro, G.; De Fazio, P. Use of atypical antipsychotics in the elderly: A clinical review. Clin. Interv. Aging, 2014, 9, 1363-1373.
[PMID: 25170260]
Kaminsky, B.M.; Bostwick, J.R.; Guthrie, S.K. Alternate routes of administration of antidepressant and antipsychotic medications; Annals Pharmcother, 2015, pp. 1-10.
Peterson, B.; Weyers, M.; Steenekamp, J.H.; Steyn, J.D.; Gouws, C. Drug bioavailability enhancing agents of natural origin (bioenhancers) that modulate drug membrane permeation and pre-systemic metabolism. Pharmaceutics, 2019, 11, 46.
Khan, S.; Baboota, S.; Ali, J.; Khan, S.; Narang, R.S.; Narang, J.K. Nanostructured lipid carriers: an emerging platform for improving oral bioavailability of lipophilic drugs. Int. J. Pharm. Investig., 2015, 5(4), 182-191.
[] [PMID: 26682188]
Yáñez, J.A.; Wang, S.W.J.; Knemeyer, I.W.; Wirth, M.A.; Alton, K.B. Intestinal lymphatic transport for drug delivery. Adv. Drug Deliv. Rev., 2011, 63(10-11), 923-942.
[] [PMID: 21689702]
Managuli, R.S.; Raut, S.Y.; Reddy, M.S.; Mutalik, S. Targeting the intestinal lymphatic system: A versatile path for enhanced oral bioavailability of drugs. Expert Opin. Drug Deliv., 2018, 15(8), 787-804.
[] [PMID: 30025212]
Muchow, M.; Maincent, P.; Muller, R.H. Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery. Drug Dev. Ind. Pharm., 2008, 34(12), 1394-1405.
[] [PMID: 18665980]
Ali Khan, A.; Mudassir, J.; Mohtar, N.; Darwis, Y. Advanced drug delivery to the lymphatic system: Lipid-based nanoformulations. Int. J. Nanomedicine, 2013, 8, 2733-2744.
[PMID: 23926431]
Patel, D.; Dasgupta, S.; Dey, S.; Ramani, Y.R.; Ray, S.; Mazumder, B. Nanostructured Lipid Carriers (NLC)- based gel for topical delivery of aceclofenac: Preparation, characterization, and in vivo evaluation. Sci. Pharm., 2012, 80(3), 749-764.
[] [PMID: 23008819]
Müller, R.H.; Radtke, M.; Wissing, S.A. Nanostructured lipid matrices for improved microencapsulation of drugs. Int. J. Pharm., 2002, 242(1-2), 121-128.
[] [PMID: 12176234]
Gaba, B.; Fazil, M.; Khan, S.; Ali, A.; Baboota, S. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull. Fac. Pharm. Cairo Univ., 2015, 53, 147-159.
Ghasemiyeh, P.; Mohammadi-Samani, S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res. Pharm. Sci., 2018, 13(4), 288-303.
[] [PMID: 30065762]
Joshi, M.; Patravale, V. Formulation and evaluation of Nanostructured Lipid Carrier (NLC)-based gel of valdecoxib. Drug Dev. Ind. Pharm., 2006, 32(8), 911-918.
[] [PMID: 16954103]
Kasongo, K.W.; Pardeike, J.; Müller, R.H.; Walker, R.B. Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers. J. Pharm. Sci., 2011, 100(12), 5185-5196.
[] [PMID: 22020815]
Sharma, A.; Baldi, A. Nanostructured lipid carriers: a review. J. Dev. Drugs, 2018, 7, 191-203.
Singh, S.; Dobhal, A.K.; Jain, A.; Pandit, J.K.; Chakraborty, S. Formulation and evaluation of solid lipid nanoparticles of a water soluble drug: zidovudine. Chem. Pharm. Bull. (Tokyo), 2010, 58(5), 650-655.
[] [PMID: 20460791]
D’Souza, S. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharmaceut., 2014.e304757
Khurana, R.K.; Bansal, A.K.; Beg, S.; Burrow, A.J.; Katare, O.P.; Singh, K.K.; Singh, B. Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: systematic development, characterization and evaluation. Int. J. Pharm., 2017, 518(1-2), 289-306.
[] [PMID: 28025072]
Dudhipala, N.; Janga, K.Y.; Gorre, T. Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artif. Cells Nanomed. Biotechnol., 2018, 46(Suppl. 2), 616-625.
[] [PMID: 29688077]
Bhalekar, M.R.; Upadhaya, P.G.; Madgulkar, A.R.; Kshirsagar, S.J.; Dube, A.; Bartakke, U.S. In-vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates of darunavir. Drug Deliv., 2016, 23(7), 2581-2586.
[PMID: 25996834]
Agarwal, S.; Harikumar, S.L.; Garg, R. Investigative study on the impact of solid:liquid lipid ratio and stabilizer amount on some important characteristics of nanaostructure lipid carriers of quetiapine fumarate. Int. J. Pharm. Investig., 2019, 9, 47-52.
Hamed, R.; AlJanabi, R.; Sunoqrot, S.; Abbas, A. The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends. Drug Dev. Ind. Pharm., 2017, 43(8), 1330-1342.
[] [PMID: 28402145]
Tran, T.H.; Ramasamy, T.; Truong, D.H.; Choi, H.G.; Yong, C.S.; Kim, J.O. Preparation and characterization of fenofibrate-loaded nanostructured lipid carriers for oral bioavailability enhancement. AAPS PharmSciTech, 2014, 15(6), 1509-1515.
[] [PMID: 25035071]
Nishimukai, M.; Hara, H.; Aoyama, Y. Enteral administration of soybean lecithin enhanced lymphatic absorption of triacylglycerol in rats. Br. J. Nutr., 2003, 90(3), 565-571.
[] [PMID: 13129462]
Tan, M.E.; He, C.H.; Jiang, W.; Zeng, C.; Yu, N.; Huang, W.; Gao, Z.G.; Xing, J.G. Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia-reperfusion injury in rats. Int. J. Nanomedicine, 2017, 12, 3253-3265.
[] [PMID: 28458544]
Kelidari, H.R.; Saeedi, M.; Akbari, J.; Morteza-semnani, K.; Valizadeh, H. Development and optimisation of Spironolactone nanoparticles for enhanced dissolution rates and stability. AAPS PharmSciTech, 2016, 18(5), 1469-1474.
[] [PMID: 27834054]
Khalil, R.M.; Abd-Elbary, A.; Kassem, M.A.; Ghorab, M.M.; Basha, M. Nanostructured Lipid Carriers (NLCs) versus Solid Lipid Nanoparticles (SLNs) for topical delivery of meloxicam. Pharm. Dev. Technol., 2014, 19(3), 304-314.
[] [PMID: 23528038]
Shah, R.; Eldridge, D.; Palombo, E.; Harding, I. Lipid nanoparticles: production, characterization and stability; Springer Int. Publish: New York, 2015.
Emami, J.; Mohiti, H.; Hamishehkar, H.; Varshosaz, J. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design. Res. Pharm. Sci., 2015, 10(1), 17-33.
[PMID: 26430454]
Akhoond Zardini, A.; Mohebbi, M.; Farhoosh, R.; Bolurian, S. Production and characterization of nanostructured lipid carriers and solid lipid nanoparticles containing lycopene for food fortification. J. Food Sci. Technol., 2018, 55(1), 287-298.
[] [PMID: 29358821]
Schubert, M.A.; Müller-Goymann, C.C. Characterisation of surface-modified Solid Lipid Nanoparticles (SLN): Influence of lecithin and nonionic emulsifier. Eur. J. Pharm. Biopharm., 2005, 61(1-2), 77-86.
[] [PMID: 16011893]
Akanda, M.H.; Rai, R.; Slipper, I.J.; Chowdhry, B.Z.; Lamprou, D.; Getti, G.; Douroumis, D. Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid nanoparticles. Int. J. Pharm., 2015, 493(1-2), 161-171.
[] [PMID: 26200751]
Sharma, S.; Shukla, P.; Misra, A.; Mishra, P.R. Interfacial and colloidal properties of emulsified systems: Pharmaceutical and biological perspective. Colloid Interface Sci. Pharmaceut. Res. Develop., Ohshima, H; Makino, K., Ed.; Elsevier: Amsterdam, 2014, pp. 149-172.
Tamjidi, F.; Shahedi, M.; Varshosaz, J.; Nasirpour, A. Design and characterization of astaxanthin-loaded nanostructured lipid carriers. Innov. Food Sci. Emerg. Technol., 2014, 26, 366-374.
Pardeike, J.; Weber, S.; Zarfl, H.P.; Pagitz, M.; Zimmer, A. Itraconazole-loaded Nanostructured Lipid Carriers (NLC) for pulmonary treatment of aspergillosis in falcons. Eur. J. Pharm. Biopharm., 2016, 108, 269-276.
[] [PMID: 27449629]
Costa, P.; Sousa, Lobo J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13(2), 123-133.
[] [PMID: 11297896]
Hashem, F.M.; Nasr, M.; Fathy, G.; Ismail, A. Formulation and in vitro and in vivo evaluation of lipid-based Tertbuline Sulphate bi-layer tablets for once-daily administration. AAPS PharmSciTech, 2016, 17(3), 727-734.
[] [PMID: 26335420]
Vivek, K.; Reddy, H.; Murthy, R.S.R. Investigations of the effect of the lipid matrix on drug entrapment, in vitro release, and physical stability of olanzapine-loaded solid lipid nanoparticles. AAPS PharmSciTech, 2007, 8(4)E83
[] [PMID: 18181544]
Das, S.; Chaudhury, A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech, 2011, 12(1), 62-76.
[] [PMID: 21174180]
Aljaeid, B.M.; Hosny, K.M. Fabrication and evaluation of phytomenadione as a nanostructure lipid carrier for enhancement of bioavailability. Pharm. Dev. Technol., 2018, 23(4), 382-386.
[] [PMID: 28346840]
Mandpe, L.; Pokharkar, V. Quality by design approach to understand the process of optimization of iloperidone nanostructured lipid carriers for oral bioavailability enhancement. Pharm. Dev. Technol., 2015, 20(3), 320-329.
[] [PMID: 24328553]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy