Open Access
Subscription Access
Open Access
Subscription Access
Development and Evaluation of Thermo Triggered in Situ Nasal Gel of Selegiline for Depressive Disorders: In Vitro, in Vivo and Ex Vivo Characterization
Subscribe/Renew Journal
In present scenario selective serotonin reuptake inhibitors are the first-choice drug for depression, but as per study of American Psychiatric Association monoamine oxidase inhibitor may be used as an antidepressant when other antidepressant trial on patient have been failed. Selegiline is both MAO-A and MOA-B inhibitor (dose dependent). Present delivery system is an in situ gelling system based on the chitosan and β-glycrophosphate. β-Glycerophosphate is used in form of di sodium salt which is a weakly basic compound which is naturally found in the body. In situ gelling system was prepared by addition of β- glycerophosphate to chitosan polymer causes conversion of pH sensitive chitosan to temperature sensitive. Developed formulations were evaluated for mucoadhesive strength, gel strength, drug content, in vitro release which was found 17.0±1.0 seconds, 6.4±0.1, 229.3±1.0 cp, 1433.3±1.2 cp, 99.45±0.4 %, 35.7±0.6 seconds, 3035.78±0.46 dyne/cm2 respectively. Histopathological studies of treated nasal mucosa of sheep revealed that selected formulation batch have no toxic effect on mucosal layer and no significant change was observed in mucosal structure. In vivo study of prepared optimized in situ gel was found more efficacious compare to marketed oral tablet of selegiline.
Keywords
In situ gel, Chitosan; Selegiline, β- glycerophosphate, Mucoadhesive strength, Gel strength.
Subscription
Login to verify subscription
User
Font Size
Information
- Bitter C, Zimmermann SK, Surber C. Nasal drug delivery in humans. Current Problems in Dermatology. 2011; 40:20–35.
- Fitzmaurice C., Global regional and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18(4):376–93
- American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). APA. Am J Psychiatry. 2000; 157(4):1–45.
- Chenite BM et al. Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions. Carbohydrate Polymers. 2001; 46(1):39-47.
- Chen X et al. Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: Preparation, characterization, and in vivo evaluation. J Biomater Appl. 2011; 27(4):391–402.
- Shastri DH, Prajapati ST. Thermoreversible mucoadhesive ophthalmic in-situ hydrogel: design and optimization using a combination of polymers. Acta Pharm.2010; 60(3):349–60.
- Athare AV et al. Formulation and evaluation of eletriptan hydrobromide thermoreversible nasal in situ gel. Int. J. Pharma. Res. Dev. 2012; 4:267-275.
- Rehman TU, Tavelin S, Gröbner G. Chitosan in situ gelation for improved drug loading and ret-ention in poloxamer 407 gels. Int J Pharm. 2011; 409(1–2):19–29.
- Marwah H et al. Development of transferosomal gel for trans-dermal deli-very of insulin using iodine complex. Drug Deliv. 2016; 23(5):1636–1644.
- Sonowal B et al. Studies on In-Situ Forming Thermo Sensitive Injectable Polymeric gel for Sustained Drug Delivery. Research J. Pharm. and Tech. 2017; 10(6): 1840-1847
- Zaki NM et al. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. European Journal of Pharmaceutical Sciences. 2007; 32: 296–307.
- Gupta SK, Singhvi IJ. Sustained Ophthalmic Delivery of Moxifloxacin Hydrochloride from a pH Triggered in Situ Gelling System. Research J. Pharm. and Tech. 5(12): Dec. 2012; Page 1538-1542.
- Liu Y et al. In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery. Aaps Pharm Sci Tech. 2010; 11(2):610-620.
- Darwhekar G et al. Development and Optimization of Dorzolamide Hydrochloride and Timolol Maleate in Situ Gel for Glaucoma Treatment. Asian J. Pharm. Ana. 2011; 1(4):93-97
- Keny RV, Lourenco CF. Formulation and evaluation of thermoreversible in situ gelling and mucoadhesive diltiazem hydrochloride liquid suppository. Int J Pharma Biol Sci. 2010; 1(1):1–17.
- Yellanki SK et al. Development of Moxifloxacin Hydrochloride in situ Opthalmic Gelling Systems Using Natural and Synthetic Polymers and In vitro Evaluation. Research J. Pharm. and Tech.2010; 3 (3):729-732.
- Yong CS et al. Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. Int J Pharm. 2001; 226(1–2):195–205.
- Mahajan N et al. Development and Evaluation of Ion Induced in Situ Gelling System of Opoid Analgesic for Nose to Brain Delivery. Research J. Pharm. and Tech. 2019; 12(10):4741-4746.
- Shelke S. et. al. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide. J Mater Sci Mater Med. 2016; 27(6):103.
- Hussain MM, Nappinai M. Development and Method Validation of an Unconventional In-Vitro Test To Measure Mucoadhesive Strength of Tablets. Research J. Pharm. and Tech.2 (2): April.-June.2009; Page 363-365.
- Ta HT et al. Chitosan-dibasic orthophosphate hydrogel: a potential drug delivery system. Int J Pharm 2009; 371:134–141.
- Bhagat BV et al. Development of Ophthalmic In Situ Gelling Formulation of Ciprofloxacin Hydrochloride Using Gellan Gum. Research J. Pharm. and Tech.2011; 4(11): 1742-1745.
- Sreelakshmi.C et al. In situ gel of Nifedipine: an approach for extended release with Zero order kinetics. Research J. Pharm. and Tech 2018; 11(4):1293-1297.
- Pisal S et al. Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride. AAPS Pharm Sci Tech. 2004; 5:1–9.
- Cheng Y et al. Development of a novel nasal nicotine formulation comprising an optimal pulsatile and sustained plasma nicotine profile for smoking cessation. J Control Release. 2002; 79:243–249.
- Majithiya RJ, Ghosh PK, Umrethia ML. Thermoreversible mucoadhesive gel for nasal delivery of sumatriptan. AAPS Pharm Sci Tech. 2006; 7:1–7.
- Dhir A, Kulkarni SK. Involvement of l arginine nitric oxide cyclic guanosine monophosphate pathway in the antidepressant-like effect of venlafaxine in mice. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007; 31:921–925.
- Mygind N, Dahl R. Anatomy, physiology and function of the nasal cavity in health and disease. Adv Drug Del Rev. 1998; 29:3–12.
- Khattab A, Marzok S, Ibrahim M. Development of optimized mucoadhesive thermosensitive pluronic based in situ gel for controlled delivery of Latanoprost: Antiglaucoma efficacy and stability approaches. J. of Drug Del. Sci. and Tech.2019; 53:101134.
- Hapse SA et al. Development of Ophthalmic In Situ Gelling Formulation of Ciprofloxacin Hydrochloride Using Gellan Gum. Research J. Pharm. and Tech.2011; 4(11):1742-1745.
- Sridhar V et al. Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson's disease. Journal of drug targeting. 2018; 26(2):150-161. 32. Kitaichi Y et al. Selegiline remarkably improved stage 5 treatment-resistant major depressive disorder: a case report. Neuropsychiatr Dis Treat. 2013; 9:1591–1594.
- Lee KC, Chen JJ. Transdermal selegiline for the treatment of major depressive disorder Neuropsychiatr Dis Treat. 2007; 3(5):527–537.
- Sharma S, Lohan S, Murthy RS. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug Dev. Ind. Pharm. 2014; 40(7):869–878.
- Lungare S, Bowen J, Badhan R. Development and evaluation of a novel intranasal spray for the delivery of amantadine. J. Pharm. Sci. 2016; 105(3):1209–1220.
- Tao T et al. Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration. Yao Xue Xue Bao. 2006; 41(11):1104–1110.
- Chen X et al. Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel. J. Pharm. Pharmacol. 2013, 65(6):807–816.
- Haque S et al. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression. J. Psychiatr. Res. 2014, 48(1):1–12.
- Dhalkar PV et al. Formulation and Evaluation of in situ Gel Model Naproxen. Research J. Pharm. and Tech. 2019; 9(3): 204-207.
Abstract Views: 347
PDF Views: 0