INVESTIGATING THE POTENTIAL OF AN ANTIDEPRESSANT INTRANASAL MUCOADHESIVE MICROEMULSION
DOI:
https://doi.org/10.22159/ijpps.2018v10i6.25710Keywords:
Blood-brain barrier, Nasal mucosa, Intranasal delivery, Microemulsion, Mucoadhesive, Duloxetine hydrochlorideAbstract
Objective: The main aim of this study was to formulate, develop and optimized a duloxetine hydrochloride (dlx-hcl) loaded mucoadhesive microemulsion intended for intranasal administration.
Methods: Established on solubility studies capmul mcm, transcutol-p, labrasol were used as oil, co-surfactant and surfactant respectively. The optimized mucoadhesive microemulsion prepared using water titration method was further characterized for particle size, polydispersity index, zeta potential and conductivity measurements followed by drug content, nasal cilio toxicity and biochemical estimation of the selected formulation.
Results: All physicochemical parameters conducted, proved that dlx-hcl microemulsion was appropriate for nasal delivery. Chitosan, used as mucoadhesive polymer demonstrated enhanced retention time of the microemulsion in nasal mucosa with no signs of toxicity and epithelial damage. The particle size and zeta potential were found to be of 200 nm and-15 mV respectively considering the formulation safe for nasal delivery.
Conclusion: This formulation strategy can be used as an effective targeting technique for the drugs having low bioavailability and poor brain penetration along with an effective method for the treatment long-term disease like depression.
Downloads
References
Bisht R. Brain drug delivery system: a comprehensive review on recent experimental and clinical findings. Int J Pharm Sci Res 2011;2:*792-806.
Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, et al. Strategy for effective brain drug delivery. Eur J Pharm Sci 2010;40:385-403.
Thorne R, Pronk G, Padmanabhan V, Frey Wn. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neurosci 2004;127:481-96.
Elshafeey AH, Bendas ER, Mohamed OH. The intranasal microemulsion of sildenafil citrate: in vitro evaluation and in vivo pharmacokinetic study in rabbits. AAPS PharmSciTech 2009;10:361-7.
Vyas TK, Babbar A, Sharma R, Misra A. Intranasal mucoadhesive microemulsions of zolmitriptan: preliminary studies on brain-targeting. J Drug Target 2005;13:317-24.
Shital Butani TS, Kunal Parmar, Amarjitsing Rajput. Development of rizatriptan benzoate microspheres for the nose to brain targeting. Int J Appl Pharm 2016;8:69-74.
Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies. J Controlled Release 2018;270:89-100.
Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA, Khan ZI. Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Delivery Formulation 2008;2:238-57.
Lin Y, Shen Q, Katsumi H, Okada N, Fujita T, Jiang X, et al. Effects of Labrasol and other pharmaceutical excipients on the intestinal transport and absorption of rhodamine123, a P-glycoprotein substrate, in rats. Biol Pharm Bull 2007;30:1301-7.
Tenjarla S. Microemulsions: an overview and pharmaceutical applications. Crit Rev Ther Drug Carr Sys 1999;16:461-521.
Lieberman HA, Rieger MM, Banker GS. Disperse systems. Pharm Dosage Forms; 1998.
Dixit GR, MATHUR VB. Microemulsions: a platform for improvement of solubility and dissolution of poorly soluble drugs. Asian J Pharm Clin Res 2015;8:7-17.
Jain DS, Bajaj AN, Tiwari N. In vitro-in vivo assessment and comparison of intranasally administered microemulsion formulations of essential oils for a migraine. Int J Curr Pharm Res 2011;3:47-51.
Jogani VV, Shah PJ, Mishra P, Mishra AK, Misra AR. Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting. Alzh Dis Assoc Disorders 2008;22:116-24.
Kumar M, Misra A, Mishra A, Mishra P, Pathak K. Mucoadhesive nanoemulsion-based intranasal drug delivery system of olanzapine for brain targeting. J Drug Target 2008;16:806-14.
Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psych Res 2002;36:383-90.
Paulzen M, Hiemke C, Gründer G. Plasma levels and cerebrospinal fluid penetration by duloxetine in a patient with a non-fatal overdose during a suicide attempt. Int J Neuropsych 2009;12:1431-2.
Lantz R, Gillespie T, Rash T, Kuo F, Skinner M, Kuan H, et al. Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Met Disp 2003;31:1142-50.
Kilts CD. Potential new drug delivery systems for antidepressants: an overview. J Clin Psych 2003;64:31-3.
Shinde RL, Bharkad GP, Devarajan PV. Intranasal microemulsion for the targeted nose to brain delivery in neurocysticercosis: the role of docosahexaenoic acid. Eur J Pharm Biopharm 2015;96:363-79.
Moghimipour E, Salimi A, Eftekhari S. Design and characterization of microemulsion systems for naproxen. Adv Pharm Bull 2013;3:63.
Karavana SY, Rencber S. A new in-situ gel formulation of itraconazole for vaginal administration. Pharmacol Pharm 2012;3:417-26.
Pathak R, Prasad Dash R, Misra M, Nivsarkar M. Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to the brain via the intranasal route. Acta Pharm Sin B 2014;4:151-60.
Mahajan HS, Mahajan MS, Nerkar PP, Agrawal A. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting. Drug Delivery 2014;21:148-54.
Jindal A, Mahesh R, Bhatt S. Etazolate, a phosphodiesterase 4 inhibitor reverses chronic unpredictable mild stress-induced depression-like behaviour and brain oxidative damage. Pharmacol Biochem Behavior 2013;105:63-70.
Valecha R, Dhingra D. Behavioral and biochemical evidence for the antidepressant-like activity of Celastrus paniculatus seed oil in mice. Basic Clin Neurosci 2016;7:*49-56.
Serchov T, Calker D, Biber K. Sucrose preference test to measure anhedonic behaviour in mice. Bio-protocol 2016;6. Doi:10.21769/BioProtoc.1958.
Brenes Sáenz JC, Villagra OR, Fornaguera TrÃas J. Factor analysis of forced swimming test, sucrose preference test and open field test on enriched, social and isolated reared rats. Behav Brain Res 2006;169:57-65.
Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem 1949;177:751-66.
Ellman GL. A colourimetric method for determining low concentrations of mercaptans. Arch Biochem Biophys 1958;74:443-50.
Wills E. Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966;99:667-76.
Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RSR. Thermoreversible-mucoadhesive Gel for nasal delivery of sumatriptan. AAPS PharmSciTech 2006;7:E80-E6.
Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharm 1978;47:379-91.
Published
How to Cite
Issue
Section
