Cargando…
Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug
The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been do...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297899/ https://www.ncbi.nlm.nih.gov/pubmed/37367128 http://dx.doi.org/10.3390/gels9060457 |
_version_ | 1785063983127986176 |
---|---|
author | Ghazwani, Mohammed Vasudevan, Rajalakshimi Kandasamy, Geetha Manusri, Naredla. Devanandan, Praveen Puvvada, Ranadheer Chowdary Veeramani, Vinoth Prabhu Paulsamy, Premalatha Venkatesan, Krishnaraju Chidmabaram, Kumarappan Dhurke, Rajeshri |
author_facet | Ghazwani, Mohammed Vasudevan, Rajalakshimi Kandasamy, Geetha Manusri, Naredla. Devanandan, Praveen Puvvada, Ranadheer Chowdary Veeramani, Vinoth Prabhu Paulsamy, Premalatha Venkatesan, Krishnaraju Chidmabaram, Kumarappan Dhurke, Rajeshri |
author_sort | Ghazwani, Mohammed |
collection | PubMed |
description | The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be −6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery. |
format | Online Article Text |
id | pubmed-10297899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102978992023-06-28 Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug Ghazwani, Mohammed Vasudevan, Rajalakshimi Kandasamy, Geetha Manusri, Naredla. Devanandan, Praveen Puvvada, Ranadheer Chowdary Veeramani, Vinoth Prabhu Paulsamy, Premalatha Venkatesan, Krishnaraju Chidmabaram, Kumarappan Dhurke, Rajeshri Gels Article The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be −6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery. MDPI 2023-06-02 /pmc/articles/PMC10297899/ /pubmed/37367128 http://dx.doi.org/10.3390/gels9060457 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ghazwani, Mohammed Vasudevan, Rajalakshimi Kandasamy, Geetha Manusri, Naredla. Devanandan, Praveen Puvvada, Ranadheer Chowdary Veeramani, Vinoth Prabhu Paulsamy, Premalatha Venkatesan, Krishnaraju Chidmabaram, Kumarappan Dhurke, Rajeshri Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title | Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title_full | Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title_fullStr | Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title_full_unstemmed | Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title_short | Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug |
title_sort | formulation of intranasal mucoadhesive thermotriggered in situ gel containing mirtazapine as an antidepressant drug |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297899/ https://www.ncbi.nlm.nih.gov/pubmed/37367128 http://dx.doi.org/10.3390/gels9060457 |
work_keys_str_mv | AT ghazwanimohammed formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT vasudevanrajalakshimi formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT kandasamygeetha formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT manusrinaredla formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT devanandanpraveen formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT puvvadaranadheerchowdary formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT veeramanivinothprabhu formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT paulsamypremalatha formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT venkatesankrishnaraju formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT chidmabaramkumarappan formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug AT dhurkerajeshri formulationofintranasalmucoadhesivethermotriggeredinsitugelcontainingmirtazapineasanantidepressantdrug |