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Inclusion complex of cyclodextrin with ergotamine and evaluation of cyclodextrin-based nanosponges

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Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Purpose

The anti-migraine drugs show first-pass metabolism, short half-life, and low bioavailability resulting in repeated dose or overdose effect. Polymeric, biodegradable and highly porous nanosponges emerge as a promising carrier for migraine treatment to improve aqueous solubility, stability and bioavailability.

Method

Ergotamine nanosponges prepared by interfacial polymerization method wherein hydroxypropyl beta-cyclodextrin inclusion complex was crosslinked using toluene diisocyanate. Caffeine used as a permeation enhancer for ergotamine by forming soluble molecular complex with cyclodextrin moiety of nanosponges. Further, nanosponges were characterized for particle size, zeta potential, entrapment efficiency, percentage drug release profile, antioxidant activity, photostability and instrumental analytical studies.

Results

Caffeine significantly improved the permeation of ergotamine nanosponges. The particle size for optimized nanosponges was 693.5 ± 11.7 nm, zeta potential of − 19.4 ± 5.69 mV with high colloidal stability and maximum entrapment efficiency of 98.88 ± 2.8%. In-vitro and ex-vivo studies exhibited controlled release profiles of ergotamine 81.6% ± 3.4% and 79% ± 4.2% for 24 h, respectively. Nanosponges demonstrated higher antioxidant activity 85.68% ± 1.23% whereas photostability data showed no significant decrease in drug content indicating good stability. Fourier transform infrared spectroscopy confirmed significant interaction of ergotamine with cyclodextrin-based nanosponges.

Conclusion

Nanosponges showed improvement in bioavailability of ergotamine and long-term stability offering inexpensive, productive and safe alternative for migraine.

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Abbreviations

ET:

Ergotamine tartrate

CD:

Cyclodextrin

HCD:

Hydroxypropyl B-cyclodextrin

NSP:

Nanosponges

CNS:

Central nervous system

5-HT:

5-Hydroxy tryptamine

CGRP:

Calcitonin gene-related peptide

TIN:

Toluene diisocvanate

TEA:

Trimethyl amine

KOH:

Potassium hydroxide

DCM:

Dichloromethane

ET-CD:

Ergotamine-cyclodextrin inclusion

NLC:

Nanostrucrured lipid carriers

SLN:

Solid-lipid nanoparticles

p MDI:

Pressurized metered-dose inhaler

FTIR:

Fourier transform infrared

DSC:

Differential scanning colorimetry

NMR:

Nuclear Magnetic Resonance

SEM:

Scanning electron microscopy

DPPH:

2,2-Dipheny1-1-picrylhydrazyl

PVDF:

Polyvinyl difluoride

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, Mumbai, India

    Preeti Dali & Pravin Shende

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  1. Preeti Dali
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  2. Pravin Shende
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Dali, P., Shende, P. Inclusion complex of cyclodextrin with ergotamine and evaluation of cyclodextrin-based nanosponges. J Incl Phenom Macrocycl Chem 102, 669–682 (2022). https://doi.org/10.1007/s10847-022-01149-y

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  • DOI: https://doi.org/10.1007/s10847-022-01149-y

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