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In Vivo Evaluation of Almotriptan malate Formulation through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment

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Abstract 

Migraine headaches are usually intolerable, and a quick-relief treatment remains an unmet medical need. Almotriptan malate is a serotonin (5-HT1B/1D) receptor agonist approved for the treatment of acute migraine in adults. It is currently available in an oral tablet dosage form and has a Tmax of 1–3 h, and therefore, there is a medical need to develop a non-invasive rapidly acting formulation. We have developed an intranasal formulation of almotriptan malate using the quality-by-design (QbD) approach. A 2-factor 3-level full factorial design was selected to build up the experimental setting. The developed formulation was characterized for pH, viscosity, in vitro permeation, ex vivo permeation, and histopathological tolerance. To assess the potential of the developed formulation to produce a rapid onset of action following intranasal delivery, a pharmacokinetic study was performed in the Sprague–Dawley rat model and compared to the currently available marketed oral tablet formulation. For this, the LC–MS/MS bioanalytical method was developed and used for the determination of plasma almotriptan malate concentrations. Results of a pharmacokinetic study revealed that intranasal administration of optimized almotriptan malate formulation enabled an almost five-fold reduction in Tmax and about seven-fold increase in bioavailability in comparison to the currently available oral tablet formulation, suggesting the potential of developed almotriptan malate intranasal formulation in producing a rapid onset of action as well as enhanced bioavailability.

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All data underlying the results are available as part of the article and no additional source data are required.

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Author information

Author notes

  1. Shubham Gupta and Akhil Perla contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research – Ahmedabad (NIPER–A), Gandhinagar, 382355, India

    Shubham Gupta, Akhil Perla, Jyotsna G. Vitore, Bharathi K, Sagar Salave, Dhwani Rana, Amit Sharma & Derajram Benival

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research – Ahmedabad (NIPER–A), Gandhinagar, 382355, India

    Abhishek Roy & Hemant Kumar

  3. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research – Ahmedabad (NIPER–A), Gandhinagar, 382355, India

    Rajeshwari Rathod

  4. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), Gandhinagar, 382355, Gujarat, India

    Derajram Benival

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  1. Shubham Gupta
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Contributions

Shubham Gupta: investigation, methodology, visualization, writing original draft.

Akhil Perla: investigation, methodology, visualization, writing original draft.

Abhishek Roy: investigation, methodology.

Jyotsna G. Vitore: writing, reviewing, and editing.

Bharathi K: reviewing, and editing.

Sagar Salave: writing, data curation, reviewing, and editing.

Dhwani Rana: reviewing, and editing.

Amit Sharma: reviewing, and editing.

Rajeshwari Rathod: investigation, reviewing.

Hemant Kumar: investigation, reviewing, visualization.

Derajram Benival: conceptualization, methodology, visualization, supervision, and editing.

Corresponding author

Correspondence to Derajram Benival.

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Ethics Approval and Consent to Participate

The study employed Sprague–Dawley rats which were treated according to standard laboratory guidelines according to a protocol approved by the Institutional Animal Ethics Committee of NIPER-A (NIPERA/IAEC/2020/031).

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The authors declare no competing interests.

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Gupta, S., Perla, A., Roy, A. et al. In Vivo Evaluation of Almotriptan malate Formulation through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment. AAPS PharmSciTech 24, 32 (2023). https://doi.org/10.1208/s12249-022-02496-2

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