DEVELOPMENT AND EVALUATION OF MUCOADHESIVE FLUNARIZINE NANOEMULSION FOR NOSE-TO-BRAIN DRUG DELIVERY IN THE MANAGEMENT OF ALZHEIMER’S DISEASE

Mudrika K; Venkata Badarinath A

doi:10.37022/jiaps.v11i1.816

K. Mudrika Department of Pharmaceutics, Santhiram College of Pharmacy (Autonomous), NH 40, Nerawada, Nandyal District, Andhra Pradesh – 518112, India
A. Venkata Badarinath Department of Pharmaceutics, Santhiram College of Pharmacy (Autonomous), NH 40, Nerawada, Nandyal District, Andhra Pradesh – 518112, India

DOI https://doi.org/10.37022/jiaps.v11i1.816

Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder characterised by memory loss and cognitive impairment. The delivery of therapeutic agents to the brain is significantly restricted by the blood–brain barrier (BBB), limiting drug effectiveness. Flunarizine, a lipophilic calcium channel blocker, exhibits potential neuroprotective activity; however, its oral bioavailability is limited due to extensive first-pass metabolism. The present study aimed to develop and evaluate a mucoadhesive nanoemulsion of Flunarizine for intranasal (nose-to-brain) drug delivery to enhance brain targeting and therapeutic efficacy. Nanoemulsions were formulated using sesame oil as the oil phase, Tween 80 as the surfactant, PEG 400 as the co-surfactant, and distilled water as the aqueous phase, employing the vortexing–sonication method. A total of nine formulations (F1–F9) were developed using an L9 Taguchi orthogonal array design. The prepared formulations were evaluated for physicochemical parameters such as pH, drug content, entrapment efficiency, particle size, polydispersity index, zeta potential, and in-vitro drug diffusion.Among the formulations, F3 demonstrated optimal characteristics, including suitable particle size, high entrapment efficiency, stability, and enhanced drug release. Drug release kinetics indicated that the optimised formulation followed zero-order kinetics with a diffusion-controlled release mechanism. The findings suggest that the developed mucoadhesive Flunarizine nanoemulsion is a promising approach for intranasal drug delivery, offering improved brain targeting and therapeutic potential in the management of Alzheimer’s disease.

Keywords: Flunarizine, Nanoemulsion, Intranasal delivery, Alzheimer’s disease,, Nose-to-brain delivery, Mucoadhesive system

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References

1. Alzheimer’s Association. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598–1695.
2. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):32.
3. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37(1):13–25.
4. Pardridge WM. The blood–brain barrier: bottleneck in brain drug development. NeuroRx. 2005;2(1):3–14.
5. Todd PA, Benfield P. Flunarizine: a reappraisal of its pharmacological properties and therapeutic use. Drugs. 1989;38(4):481–499.
6. Goa KL, Ward A. Flunarizine: a review of its pharmacodynamic and pharmacokinetic properties. Drugs. 1987;33(6):541–573.
7. Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci. 2000;11(1):1–18.
8. Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective. Ther Deliv. 2013;4(1):99–117.
9. Shakeel F, Ramadan W, Ahmed MA. Investigation of true nanoemulsions for transdermal delivery of an anti-hypertensive drug. Int J Pharm. 2009;377(1–2):1–6.
10. Gupta A, Eral HB, Hatton TA, Doyle PS. Nanoemulsions: formation, properties, and applications. Soft Matter. 2016;12:2826–2841.
11. Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm. 2009;71(3):505–518.
12. Hanson LR, Frey WH. Intranasal delivery bypasses the blood–brain barrier to target therapeutic agents to the central nervous system. BMC Neurosci. 2008;9(Suppl 3):S5.
13. Lakhera P, Narwal S, Tuteja M. Preformulation studies and validation of UV spectrophotometric method of amoxicillin trihydrate. Indian Drugs. 2024;61(5):52–60.
14. Mohamed AI, et al. Investigation of drug–polymer compatibility using UV-spectrophotometric method. J Pharm Anal. 2017;7(3):164–170.
15. Segall AI. Preformulation studies: use of FTIR in drug–excipient compatibility. J Appl Pharm Sci. 2019;4(3):1–6.
16. Khedekar PB, Saudagar RB. Evaluation of compatibility of diltiazem hydrochloride with excipients by FTIR and DSC. World J Pharm Pharm Sci. 2018;7(10):664–675.
17. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. Biotech. 2015;5(2):123–127.
18. Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nanoemulsions. Adv Colloid Interface Sci. 2004;108–109:303–318.
19. Shakeel F, Ramadan W. Nanoemulsions as potential drug delivery systems. Saudi Pharm J. 2010;18(4):179–183.
20. Patel RP, Patel MM. Spectrophotometric methods for drug analysis: a review. Asian J Pharm Clin Res. 2012;5(4):8–14.
21. Verma RK, Garg S. Drug–excipient compatibility studies in formulation development. J Pharm Biomed Anal. 2005;38(3):633–644.
22. Araújo AAS, et al. Thermal and FTIR compatibility studies of drugs with excipients. Int J Pharm. 2003;260:303–314.
23. Gondaliya D, Pundarikakshudu K. Formulation and evaluation of drug delivery systems: compatibility approach. Pharm Technol. 2014;1(1):16–25.