Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the Management of Schizophrenia

Author(s): Sarbjot Kaur, Ujjwal Nautiyal, Pooja A. Chawla, Viney Chawla*

Journal Name: Current Molecular Pharmacology

Volume 14 , Issue 3 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain.

Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia.

Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out.

Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460, respectively. The encapsulation efficiency of formulation S6 was found to be 87.25%. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96%, respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%.

Conclusion: These results reveal the potential application of novel olanzapine-NLC in intranasal drug delivery system for the treatment of Schizophrenia.

Keywords: Olanzapine, schizophrenia, nanostructured lipid carriers, taguchi experimental design, X-ray diffraction, ciliotoxicity.

Zhu, Y.; Liang, X.; Lu, C.; Kong, Y.; Tang, X.; Zhang, Y.; Yin, T.; Gou, J.; Wang, Y.; He, H. Nanostructured lipid carriers as oral delivery systems for improving oral bioavailability of nintedanib by promoting intestinal absorption. Int. J. Pharm., 2020, 586, 119569.
[] [PMID: 32592899]
Houacine, C.; Adams, D.; Singh, K.K. Impact of liquid lipid on development and stability of trimyristin nanostructured lipid carriers for oral delivery of resveratrol. J. Mol. Liq., 2020, 113734.
Eid, R.K.; Ashour, D.S.; Essa, E.A.; El Maghraby, G.M.; Arafa, M.F. Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis. Carbohydr. Polym., 2020, 232, 115826.
[] [PMID: 31952620]
Salvi, V.R.; Pawar, P. Nanostructured lipid carriers (NLC) system: A novel drug targeting carrier. J. Drug Deliv. Sci. Technol., 2019, 51, 255-267.
Puglia, C.; Blasi, P.; Rizza, L.; Schoubben, A.; Bonina, F.; Rossi, C.; Ricci, M. Lipid nanoparticles for prolonged topical delivery: An in vitro and in vivo investigation. Int. J. Pharm., 2008, 357(1-2), 295-304.
[] [PMID: 18343059]
Mukherjee, S.; Ray, S.; Thakur, R.S. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J. Pharm. Sci., 2009, 71(4), 349-358.
[] [PMID: 20502539]
Hirlekar, R.; Garse, H.; Kadam, V. Solid lipid nanoparticles and nanostructured lipid carriers: a review. Curr. Drug Ther., 2011, 6(4), 240-250.
Souto, E.B.; Müller, R.H. Investigation of the factors influencing the incorporation of clotrimazole in SLN and NLC prepared by hot high-pressure homogenization. J. Microencapsul., 2006, 23(4), 377-388.
[] [PMID: 16854814]
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]
Bhana, N.; Perry, C.M. Olanzapine: a review of its use in the treatment of bipolar I disorder. CNS Drugs, 2001, 15(11), 871-904.
[] [PMID: 11700151]
Kilickap, E. Optimization of cutting parameters on delamination based on Taguchi method during drilling of GFRP composite. Expert Syst. Appl., 2010, 37(8), 6116-6122.
Pandey, S.S.; Patel, M.A.; Desai, D.T.; Patel, H.P.; Gupta, A.R.; Joshi, S.V.; Shah, D.O.; Maulvi, F.A. Bioavailability enhancement of repaglinide from transdermally applied nanostructured lipid carrier gel: Optimization, in vitro and in vivo studies. J. Drug Deliv. Sci. Technol., 2020, 101731.
Espinosa-Olivares, M.A.; Delgado-Buenrostro, N.L.; Chirino, Y.I.; Trejo-Márquez, M.A.; Pascual-Bustamante, S.; Ganem-Rondero, A. Nanostructured lipid carriers loaded with curcuminoids: Physicochemical characterization, in vitro release, ex vivo skin penetration, stability and antioxidant activity. Eur. J. Pharm. Sci., 2020, 155, 105533.
[] [PMID: 32871214]
Otarola, J.J.; Solis, A.K.; Farias, M.E.; Garrido, M.; Correa, N.M.; Molina, P.G. Piroxicam-loaded nanostructured lipid carriers gel: Design and characterization by square wave voltammetry. Colloids Surf. A Physicochem. Eng. Asp., 2020, 606, 125396.
Nasal Drug Delivery: A Review. Indian Drugs., 2001, 38(6), 283-287.
Vyas, T.K.; Shahiwala, A.; Marathe, S.; Misra, A. Intranasal drug delivery for brain targeting. Curr. Drug Deliv., 2005, 2(2), 165-175.
[] [PMID: 16305417]
Intakhab Alam, M.; Baboota, S.; Ahuja, A.; Ali, M.; Ali, J.; Kaur Sahni, J. Nanostructured lipid carrier containing CNS acting drug: Formulation, optimization and evaluation. Curr. Nanosci., 2011, 7(6), 1014-1027.
Anuradha, K.; Kumar, M.S. Development of Lacidipine loaded nanostructured lipid carriers (NLCs) for bioavailability enhancement. Int. J. Pharm. Med. Res., 2014, 2(2), 50-57.
Devkar, T.B.; Tekade, A.R.; Khandelwal, K.R. Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer. Colloids Surf. B Biointerfaces, 2014, 122, 143-150.
[] [PMID: 25033434]
Singhvi, G.; Singh, M. In-vitro drug release characterization models. Int. J. Pharm. Stud. Res., 2011, 2(1), 77-84.
Dash, S.; Murthy, P.N.; Nath, L.; Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm., 2010, 67(3), 217-223.
[PMID: 20524422]
Jawahar, N.; Meyyanathan, S.N.; Senthil, V.; Gowthamarajan, K.; Baruah, U.K.; Elango, K. Improved Oral Bioavailability of PLGA-Nanoparticles Containing a Typical Antipsychotic Agent. Int. J. Biol. Pharm. Res., 2013, 4(12), 938-945.
Patel, R.B.; Patel, M.R.; Bhatt, K.K.; Patel, B.G. Formulation and evaluation of Microemulsion based Drug Delivery system for intra nasal administration of Olanzapine. Int. J. Biomed. Pharm. Sci., 2013, 7(1), 20-27.
Jain, K.; Sood, S.; Gowthamarajan, K. Optimization of artemether-loaded NLC for intranasal delivery using central composite design. Drug Deliv., 2015, 22(7), 940-954.
[] [PMID: 24512368]
Vyas, T.K.; Babbar, A.K.; Sharma, R.K.; Singh, S.; Misra, A. Intranasal mucoadhesive microemulsions of clonazepam: Preliminary studies on brain targeting. J. Pharm. Sci., 2006, 95(3), 570-580.
[] [PMID: 16419051]
Silverstein, R.M.; Webster, F.X. Spectrometric identification of organic compounds, 6th ed; John Wiley and Sons, 2005.
Zhang, L.; He, R.; Gu, H.C. Oleic acid coating on the monodisperse magnetite nanoparticles. Appl. Surf. Sci., 2006, 253(5), 2611-2617.
Newa, M.; Bhandari, K.H.; Oh, D.H.; Kim, Y.R.; Sung, J.H.; Kim, J.O.; Woo, J.S.; Choi, H.G.; Yong, C.S. Enhanced dissolution of ibuprofen using solid dispersion with poloxamer 407. Arch. Pharm. Res., 2008, 31(11), 1497-1507.
[] [PMID: 19023548]
Banerjee, T.; Mitra, S.; Kumar Singh, A.; Kumar Sharma, R.; Maitra, A. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int. J. Pharm., 2002, 243(1-2), 93-105.
[] [PMID: 12176298]
Tetyczka, C.; Hodzic, A.; Kriechbaum, M.; Juraić, K.; Spirk, C.; Hartl, S.; Pritz, E.; Leitinger, G.; Roblegg, E. Comprehensive characterization of nanostructured lipid carriers using laboratory and synchrotron X-ray scattering and diffraction. Eur. J. Pharm. Biopharm., 2019, 139, 153-160.
[] [PMID: 30905779]
Jäntschi, L. Structure-property relationships for solubility of monosaccharides. Appl. Water Sci., 2019, 9(2), 38.
Prajapati, S.T.; Pathak, S.P.; Thakkar, J.H.; Patel, C.N. Nanoemulsion based intranasal delivery of risperidone for nose to brain targeting. Bull. Pharm. Res., 2015, 5(1), 6-13.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 20 January, 2021
Page: [439 - 447]
Pages: 9
DOI: 10.2174/1874467214666210120160016
Price: $65

Article Metrics

PDF: 150