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Development and Evaluation of Thermoreversible Ethosomal Gel of Donepezil Hydrochloride for Intranasal Delivery

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Abstract

Purpose

The main aim of the present study was to formulate Donepezil Hydrochloride (DH)–loaded ethosomal intranasal gel to increase the transport of the drug through the blood–brain barrier (BBB), thus decreasing plasma fluctuation and also decreasing the oral side effects associated with the drug.

Methods

DH-loaded ethosomes were prepared by ethanol injection method. Nine ethosomal formulations were prepared containing three different concentrations of Phospholipon 90G and ethanol in combination and were evaluated for vesicle size, %entrapment efficiency, and drug content. The optimized ethosomal formulation was incorporated into the gelling base containing Poloxamer 407 (18%) and Poloxamer 188 (6%) as thermosensitive polymers and Carbopol 934 (0.1–0.5%) as mucoadhesive polymer. The prepared gels were further evaluated for gelation temperature, gelation time, drug content, mucoadhesive strength, viscosity, in vitro drug release, and ex vivo drug permeation study through the sheep nasal mucosa.

Results

The optimized ethosomal formulation F4 showed a vesicle size of 110.06 ± 1.910 and a % entrapment efficiency of 70.02 ± 0.353. The mucoadhesive strength and gelation temperature were found to be 3332 ± 4.314 and 31.7 ± 0.033 in the case of optimized gel formulation. The in vitro and ex vivo drug permeation from the optimized gel formulation was almost 100% after a period of 24 h.

Conclusion

Formulated DH-loaded ethosomal intranasal gel could serve as the better alternative for the brain targeting via the intranasal route.

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Abbreviations

DH:

Donepezil Hydrochloride

FDA:

Food and Drug Administration

AD:

Alzheimer’s Disease

CNS:

Central Nervous System

KBr:

Potassium Bromide

FTIR:

Fourier Transform Infrared Spectroscopy

UV:

Ultraviolet

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Acknowledgements

The authors would like to thank KLE College of Pharmacy, Belagavi, Karnataka, for providing facilities to conduct this research work. The authors are also thankful to Wockhardt Research Centre, Aurangabad (Maharashtra, India), and Lipoid (Germany) for providing gift sample of donepezil hydrochloride and Phospholipon 90G respectively.

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Authors and Affiliations

  1. Department of Pharmaceutics, KLE College of Pharmacy, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi, 560010, Karnataka, India

    Arka Gangopadhyay, Panchaxari M. Dandagi & Kishori P. Sutar

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  1. Arka Gangopadhyay
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  2. Panchaxari M. Dandagi
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  3. Kishori P. Sutar
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All authors have equal contribution to this research work. All authors read and approved the final manuscript.

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Correspondence to Kishori P. Sutar.

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Gangopadhyay, A., Dandagi, P.M. & Sutar, K.P. Development and Evaluation of Thermoreversible Ethosomal Gel of Donepezil Hydrochloride for Intranasal Delivery. J Pharm Innov 18, 238–246 (2023). https://doi.org/10.1007/s12247-022-09636-y

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