Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

DOI:

https://doi.org/10.37285/ijpsn.2020.13.6.10

Authors

  • Ashwin Kumar Tulasi
  • Anil Goud Kandhula
  • Ravi Krishna Velupula

Abstract

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was   88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Topiramate, nanoparticles, intranasal administration, mucoadhesion, epilepsy

Downloads

Published

2020-11-16

How to Cite

1.
Tulasi AK, Kandhula AG, Velupula RK. Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery. Scopus Indexed [Internet]. 2020 Nov. 16 [cited 2024 Dec. 11];13(6):5250-5. Available from: https://www.ijpsnonline.com/index.php/ijpsn/article/view/1165

Issue

Section

Research Articles

References

AI-Nemrawi NK, Alsharif SS and Dave RH (2018). Preparation of chitosan-TPP nanoparticles: the influence of chitosan polymeric properties and formulation variables. Int J App Pharm 10(5): 60-5.

Arun B, Narendar D, and Kishan V (2017). Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation. Artif cells Nanomed Biotechnol 46: 126-137.

Ashwin KT and Anil Goud K (2018) Formulation and characterization of paliperidone loaded mucoadhesive microemulsion for intranasal delivery. Int J Pharm and Bio Sci 8(2): 844-849

Bagul U, Gujar K, Dhat S, Aphale S and Bhavsar M (2009). In vitro study of mucoadhesive strength of polymers for mucoadhesive drug delivery systems. Int J Curr Pharm Res 1: 42-6.

Belgamwar VS, Patel HS, Joshi AS, Agrawal A, Surana SJ and Tekade AR (2011). Design and development of nasal mucoadhesive microspheres containing tramadol HCl for CNS targeting. Drug Deliv 18(5): 353-360.

Bhuva F, Patel LD and Patel K (2018). Factorial Design Methodology for Development of Pediatric Nasal Spray: Study on Xylometazoline Nasal Solution Used for Treatment of Nasal Congestion. Indian J Pharm Edu Res 52(2): 218-229.

Chinna Reddy P, Ramesh G, Narender D, Vamshi Vishnu Y, and Madhusudan Rao Y (2011). Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: in vitro, ex vivo and in vivo characterization. Arch Pharm Res 34(10): 1701-1710, 2011.

Dhanda DS, Frey WH, Leopold D and Kompella UB (2005). Approaches for drug deposition in the human olfactory epithelium. Drug Deliv Technol 5(4): 64-72.

Dudhipala N (2019). A comprehensive review on solid lipid nanoparticles as delivery vehicle for enhanced pharmacokinetic and pharmacodynamic activity of poorly soluble drugs. Int J Pharm Sci Nanotech 12(2): 4421-4440.

Dudhipala N and Janga KY (2017). Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: Optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm 43(7): 1205-1214.

El-din EY and Omar AR (2017). Effect of Prenatal Administration of Therapeutic Dose of Topiramate On Placentae Albino Rats’ Fetuses. Int J Pharm Pharma Sci 9(3): 54-59.

Fisher RS and Ho J (2002). Potential new methods for antiepileptic drug delivery. CNS Drugs 16(9): 579-593.

Gautam S, Nikalaje Y, Bhadre D, Trivedi R, Umekar M and Taksande J (2019) Development and evaluation of lamotrigine soya lecithin solid dispersion: in vitro and pharmacodynamic investigation. Int J App Pharm 12(1): 115-122.

Gavini E, Rassu G, Sanna V, Cossu M and Giunchedi P (2005). Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies. J Pharma Pharmacol 57(3):287-94.

Hagesaether E (2011). Permeation modulating properties of natural polymers–effect of molecular weight and mucus. Int J pharm 409(1-2):150-5.

Janapareddi K and Kandhula A (2019). Development and Ex vivo evaluation of Rasagiline Mesylate mucoadhesive microemulsion for intranasal delivery using Box-Behnken design. Int J Bio Pharm Res 8(3): 2514-22.

Kandhula A and Nippani AD (2019). Development and evaluation of Zotepine loaded mucoadhesive microemulsion for intranasal delivery. J drug deliv Ther 9(4S): 54-8.

Kulkarni A, Bambole VA and Mahanwar PA (2010). Electrospinning of polymers, their modeling and applications. Polymer-Plastics Tech Eng 49(5): 427-441.

López T, Cuevas JL, Jardón G, Gómez E and Ramirez P (2017). Preparation and Characterization of Antiepileptic Drugs Encapsulated in Sol-Gel Titania Nanoparticles as Controlled Release System. Med chem 2: 003.

Ma L and Liu C (2010). Preparation of chitosan microspheres by ionotropic gelation under a high voltage electrostatic field for protein delivery. Colloids and Surfaces B: Biointer 75: 448-53.

Mantry S and Balaji A (2017). Formulation Design and Characterization of Ropinirole Hydrochoride Microsphere for Intranasal Delivery. Asian J Pharm Clin Res 10(7):195-203.

Musumeci T, Bonaccorso A and Puglisi G (2019). Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview. Pharmaceutics 11(3): 118.

Nagaraj K, Narendar D, and Kishan V (2017). Development of olmesartan medoxomil optimized nanosuspension using Box-Behnken design to improve oral bioavailability. Drug Dev Ind Pharm 43(7): 1186-1196.

Narendar D, and Kishan V (2014). Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Deliv 23: 395-404.

Narendar D, and Kishan V (2017). Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. Eur J Pharm Biopharm 110: 47-57.

Narendar D, and Thirupathi G (2020). Neuroprotective effect of ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics 12(5): 448.

Pardeshi CV and Belgamwar VS (2016). Controlled synthesis of N, N, N-trimethyl chitosan for modulated bio adhesion and nasal membrane permeability. Int J Bio Macromol 82: 933-944.

Pitta SK, Dudhipala N, Narala A, and Veerabrahma K (2018). Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm 44(3): 484-492.

Raj BS, Punitha IS, and Bodiwala J (2012). Formulation and evaluation of chitosan prazosin beads by ionotropic gelation method. Int J Res Pharm Chem 2: 974-83.

Santos-Magalhaes NS, Pontes A, Pereira VM, and Caetano MN (2000). Colloidal carriers for benzathine penicillin G: nanoemulsions and nanocapsules. Int J pharm 208(1-2): 71-80.

Sommer BR, Mitchell EL, and Wroolie TE (2013). Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity. Ther Adv Neu Dis 6(4): 211-227.

Soni M, Majumdar A, and Malviya N (2018). Mucoadhesive Chitosan Microspheres of Gefitinib. Int J Current Pharm Res 10: 9-19.

Taksande JB, and Umekar MJ (2018). Preparation of intranasal pregabalin microspheres: In vitro, ex vivo and in vivo pharmacodynamic evaluation. J Pharm Res 12(1): 112-121.

Taksande JB, Sonwane PP, Trivedi RV, Wadher KJ, and Umekar MJ (2017). Formulation and Pharmacodynamic Investigations of Lamotrigine Microspheres in Pentylenetetrazole-Induced Seizures in Mice. Asian J Pharm 11(1): S216-224.

Taksande JB, Wadher KJ, Trivedi RV, and Umekar MJ (2017). Development and Evaluation of Lamotrigine loaded N-Trimethyl Chitosan Microspheres for Intranasal Administration. Int J Chem Tech Research 10(2): 01-13.

Tas C, Ozkan CK, Savaser A, Ozkan Y, Tasdemir U, and Altunay H (2009). Nasal administration of metoclopramide from different dosage forms: in vitro, ex vivo, and in vivo evaluation. Drug deliv 16(3):167-75.

Tatke A, Dudhipala N, Janga KY, and et al (2019). In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: tear kinetics and ocular disposition studies. Nanomaterials 27: 9(1).

Thirupathi G, Swetha E and Narendar D (2017). Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats. Drug res 67(03): 163-169.

Tiyaboonchai, W (2013). Chitosan nanoparticles: A promising system for drug delivery. Naresuan University J 11: 51-66.