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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Author(s): Shweta Agarwal*, Rayasa S. Ramachandra Murthy, Sasidharan Leelakumari Harikumar and Rajeev Garg

Volume 16 , Issue 1 , 2020

Page: [73 - 91] Pages: 19

DOI: 10.2174/1573409915666190722122827

Price: $65


Background: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first-pass metabolism resulting in enhanced bioavailability.

Objective: The present work aimed at developing, and characterising potentially lymphatic absorbable Solid Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach.

Methods: Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively. A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months.

Results: The optimised formula derived for SLN had 270mg Precirol ATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetics (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for storage and preserving important characteristics within acceptable limits.

Conclusion: Development and optimisation by Quality by Design were justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

Keywords: Quetiapine fumarate, solid lipid nanoparticles, percent entrapment efficiency, precirol ATO5, phospholipon 90G, quality by design.

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Aboti, P.; Shah, P.; Patel, D.; Dalwadi, S. Quetiapine fumarate loaded solid lipid nanoparticles for improved oral bioavailability. Drug Deliv. Lett., 2014, 2, 170-184.
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]
Lohan, S.; Sharma, S.; Murthy, R.S.R. Formulation and evaluation of solid lipid nanaoparticles of quetiapine fumarate and quetiapine hemifumarate for brain delivery in rat model. Pharm. Nanotechnol., 2013, 3, 239-247.
Mauri, M.C.; Paletta, S.; Pace, C.D.; Reggiori, A.; Cernigliaro, G.; Valli, I.; Altamura, A.C. Clinical pharmacokinetics of atypical antipsychotics: An Update. Clin. Pharmacokinetics; , 2018, 6, p. 36 pages.
Burns, M.J. The pharmacology and toxicology of atypical antipsychotic agents. J. Toxicol. Clin. Toxicol., 2001, 39(1), 1-14.
[] [PMID: 11327216]
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]
Pacher, P.; Kecskemeti, V. Cardiovascular side effects of new antidepressants and antipsychotics: New drugs, old concerns? Curr. Pharm. Des., 2004, 10(20), 2463-2475.
[] [PMID: 15320756]
Trevaskis, N.L.; Charman, W.N.; Porter, C.J.H. Lipid-based delivery systems and intestinal lymphatic drug transport: A mechanistic update. Adv. Drug Deliv. Rev., 2008, 60(6), 702-716.
[] [PMID: 18155316]
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]
Nanjwade, B.K.; Patel, D.J.; Udhani, R.A.; Manvi, F.V. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci. Pharm., 2011, 79(4), 705-727.
[] [PMID: 22145101]
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]
Muller, R.H. Lipid nanoparticles: Recent advances. Adv. Drug Deliv. Rev., 2007, 59, 375-376.
Singhal, G.B.; Patel, R.P.; Prajapati, B.G.; Patel, N.A. Solid lipid nanaoparticles and nano lipid carriers: As novel solid based drug carrier. Int. Res. J Pharm., 2011, 2, 40-52.
Lin, C.H.; Chen, C.H.; Lin, Z.C.; Fang, J.Y. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. Yao Wu Shi Pin Fen Xi, 2017, 25(2), 219-234.
[] [PMID: 28911663]
O’Driscoll, C.M. Lipid-based formulations for intestinal lymphatic delivery. Eur. J. Pharm. Sci., 2002, 15(5), 405-415.
[] [PMID: 12036717]
Mishra, A.; Vuddanda, P.R.; Singh, S. Intestinal lymphatic delivery of Praziquantel by solid lipid nanoparticles: Formulation design, in vitro and in vivo studies. J. Nanotech., 2014, 2, 12.
Paliwal, R.; Rai, S.; Vaidya, B.; Khatri, K.; Goyal, A.K.; Mishra, N.; Mehta, A.; Vyas, S.P. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine (Lond.), 2009, 5(2), 184-191.
[] [PMID: 19095502]
Alex, M.R.A.; Chacko, A.J.; Jose, S.; Souto, E.B. Lpoinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur. J. Pharm. Sci., 2011, 1-2, 11-18.
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]
Padhye, S.G.; Nagarsenker, M.S. Simvastatin solid lipid nanoparticles for oral delivery: Formulation development and in vivo evaluation. Indian J. Pharm. Sci., 2013, 75(5), 591-598.
[PMID: 24403661]
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]
Costa, P.; Sousa, Lobo. J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13(2), 123-133.
[] [PMID: 11297896]
Manjunath, K.; Reddy, J.S.; Venkateswarlu, V. Solid lipid nanoparticles as drug delivery systems. Methods Find. Exp. Clin. Pharmacol., 2005, 27(2), 127-144.
[] [PMID: 15834465]
Cai, S.; Yang, Q.; Bagby, T.R.; Forrest, M.L. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles. Adv. Drug Deliv. Rev., 2011, 63(10-11), 901-908.
[] [PMID: 21712055]
Mercuri, A.M. Quality by design appied to ocular solid lipid nanoparticles containing a hydrophilic peptide prepared via hot high pressure homogeniser. Curr. Drug Deliv., 2016, 13(8), 1247-1260.
[] [PMID: 27012669]
Deshkar, S.S.; Quazi, N.A.; Patil, A.T.; Poddar, S.S. Effect of gelucire 44/14 on fluconazole solid lipid nanoparticles: Formulation, optimization and in vitro chatacterization. Drug Deliv. Lett., 2015, 5, 173-187.
Singh, I.; Swami, R.; Khan, W.; Sistla, R. Lymphatic system: A prospective area for advanced targeting of particulate drug carriers. Expert Opin. Drug Deliv., 2014, 11(2), 211-229.
[] [PMID: 24350774]
Saraf, S.; Ghosh, A.; Kaur, C.D.; Saraf, S. Novel modified nanosystem based lymphatic targeting. Res. J. Nanosci. Nanotechnol., 2011, 1-14.
Shah, R.; Eldridge, D.; Palombo, E.; Harding, I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. J. Phy. Sci., 2014, 1, 59-75.
Schwarz, C.; Mehnert, W.; Lucks, J.S.; Muller, R.H. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J. Control. Release, 1994, 1, 83-96.
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]
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]
Yusuf, M.; Sharma, V.; Pathak, K. Nanovesicles for transdermal delivery of felodipine: Development, characterization, and pharmacokinetics. Int. J. Pharm. Investig., 2014, 4(3), 119-130.
[] [PMID: 25126525]
S.M.. Noronha, C.M.; Floriani, C.L.; Lino, R.C.; Rocha, G.; Bellettini, I.C; Ogliari, P.J.; Barreto, P.L.M. Optimisation of α-tocopherol loaded solid lipid nanoparticles by central composite design. Ind. Crops Prod., 2013, 49, 278-285.
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 Pharm Sci Tech, 2007, 8(4)E83
[] [PMID: 18181544]

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