Intranasal mucoadhesive microemulsion of mirtazapine: Pharmacokinetic and pharmacodynamic studies

Hetal P Thakkar, Arpita A Patel, Nirav P Chauhan

Abstract


The aim of this investigation was to prepare and characterize mirtazapine microemulsion for intranasal delivery, to determine its brain drug delivery using pharmacokinetic studies, and assess its performance pharmacodynamically for
the antidepressant activity. Mirtazapine microemulsion of different compositions were prepared by water titration method and characterized for globule size and zeta potential. Microemulsion with maximum drug solubilization, lowest globule
size and lowest zeta potential was considered optimal and taken for further studies with or without addition of chitosan,a mucoadhesive agent. Pharmacokinetics of optimized mirtazapine microemulsion, mucoadhesive microemulsion and mirtazapine solution were studied in brain and blood of male Wistar rats post intranasal and oral administration. Despair Swim test, locomotor activity and plus maze test were carried out in rats in order to compare therapeutic activity of the drug formulation for oral and intranasal route. Brain/blood uptake ratios were found to be highest for mirtazapine mucoadhesive
microemulsion (MMME) followed by mirtazapine microemulsion (MME) post‐intranasal administration compared to oral delivery of microemulsion. Significant (P < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of MMME against control group. This investigation demonstrates a more rapid and larger extent of transport of mirtazapine into the brain with intranasal MMME, which may prove useful in treating depression.


Full Text:

PDF

References


Available from: http://en.wikipedia.org/wiki/Anxiety. [Last accessed on

Jan 2].

Loscher W, Potschka H. Role of drug efflux transporters in the brain

for drug disposition and treatment of brain diseases. Prog Neurobiol

;76:22‐76.

Misra A, Ganesh S, Shahiwala A, Shah SP. Drug delivery to the central

nervous system: A review. J Pharm Pharm Sci 2003;6:252‐73.

Vyas TK, Shahiwala A, Misra A, Marathe S. Intranasal drug delivery of

brain targeting. Curr Drug Deliv 2005;2:165‐75.

Illum L. Transport of drugs from the nasal cavity to the central nervous

system. Eur J Pharm Sci 2000;11:1‐18.

Ugwoke MI, Kinget R. The biopharmaceutical aspects of nasal

mucoadhesive drug delivery. J PharmPharmacol 2001;53:3‐21.

Anaisa P, Fortuna A, Gilberto A, Falcao A. Intranasal drug delivery: How,

why and what for? J Pharm Pharm Sci 2009;12:288‐311.

Wermeling DP, Miller JL, Rudy AC. Systematic intranasal drug delivery:

Concepts and applications. Drug Deliv Tech 2002;2:56‐61.

Joshi HM, Bhumkar DR, Joshi K, Pokharkar V, Sastry M. Gold

nanoparticles as carriers for efficient transmucosal insulin delivery.

Langmuir 2006;22:300‐5.

Mehta SK, Kaur G, Bhasin KK. Incorporation of Antitubercular Drug

Isoniazid in Pharmaceutically Accepted Microemulsion: Effect on

microstructure and physical parameters. Pharm Res 2008;25:227‐36.

Vyas TK, Babbar AK, Sharma RK, Singh S, Misra AN. Preliminary brain

targeting studies on intranasal mucoadhesive microemulsions of

sumatriptan. AAPS PharmSciTech 2006;7:E1‐9.

Vyas TK, Babbar AK, Sharma RK, Misra AN. Intranasal

mucoadhesivemicroemulsions of zolmitriptan: Preliminary studies on

brain‐targeting. J Drug Target 2005;13:317‐24.

Sharma G, Mishra AK, Mishra P, Mishra AN. Intranasal Cabergoline:

Pharmacokinetic and Pharmacodynamic studies. AAPS PharmSciTech

;10:1321‐30.

Vyas TK, Babbar AK, Sharma RK, Singh S, Misra AN. Intranasal

mucoadhesive microemulsions of clonazepam: Preliminary studies on

brain targeting. J Pharm Sci 2006;95:570‐80.

Zhang Q, Jiang X, Xiang W, Lu W, Su L, Shi Z. Preparation of

Nimodipine‐loaded microemulsion for intranasal delivery and evaluation

of the targeting efficiency to brain. Int J Pharm 2004;275:85‐96.

Jogani V, Shah P, Mishra P, Misra AN. Intranasal mucoadhesive

microemulsion of tacrine to improve brain targeting. Alzheimer Dis

Assoc Disord 2008;22:116‐24.

Lianli, Nandi I, Kim KH. Development of an ethyl laurate‐based

microemulsion for rapid‐onset intranasal delivery of diazepam. Int J

Pharm 2002;237:77‐85.

Illum L. Nasal drug delivery−possibilities, problems and solutions.

J Control Release 2003;87:187‐98.

Available from: http://en.wikipedia.org/wiki/Mirtazapine. [Last accessed

on 2011 Mar 2].

Rolan I, Piel G, Delattre L, Evrard B. Systemic characterization

of oil‐in‐water emulsions for formulation design. Int J Pharm

;263:85‐94.

Songkro S, Junyaprasert VB, Boonme P, Krauel K, Rades T. Transdermal

delivery of hydrophobic and hydrophilic local anesthetics from

o/w and w/o Brij 97‐based microemulsions. J Pharm Pharm Sci

;10:288‐98.

Vogel HG. Drug discovery and evaluation: Pharmacological assays.

rd ed. New York: Springer Publications; 2008. p. 622‐789.

Keck PE, Elray LM. Clinical pharmacodynamics and pharmacokinetics

of antimanic and mood stabilizing medications. J Clin Psychiatry

;63:1‐11.

Leong KW, Bowman K. Chitosan nanoparticles for oral drug and gene

delivery. Int J Nanomedicine 2006;1:117‐28.

Patel Z, Patel K, Shah A, Surti I. Preparation and optimization of

microemulsion of Rosuvastatin Calcium. J Pharm Bioallied Sci

;4:118‐9.

Kothari S, Minda M, Tonpay S. Anxiolytic and antidepressant activities

of methanol extract of AegleMarmelos leaves in mice. Indian J Physiol

Pharmacol 2010;54:318‐28.

Bali V, Bhavna, Ali M, Baboota S, Ali J. Potential of microemulsion in

drug delivery and therapeutics: A patent review. Recent Pat Drug Deliv

Formul 2008;2:136‐44.

Peltola S, Saarinen‐Savolainen P, Kiesvaara J, Suhonen TM, Urtti A.

Microemulsions for topical delivery of estradiol. Int J Pharm

;254:99‐107.




DOI: http://dx.doi.org/10.22377/ajp.v7i1.38

Refbacks

  • There are currently no refbacks.