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Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole

The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such d...

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Autores principales: Khare, Purva, Chogale, Manasi M., Kakade, Pratik, Patravale, Vandana B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089292/
https://www.ncbi.nlm.nih.gov/pubmed/35538191
http://dx.doi.org/10.1007/s13346-022-01155-0
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author Khare, Purva
Chogale, Manasi M.
Kakade, Pratik
Patravale, Vandana B.
author_facet Khare, Purva
Chogale, Manasi M.
Kakade, Pratik
Patravale, Vandana B.
author_sort Khare, Purva
collection PubMed
description The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such drugs by increasing the contact time of the formulation. Herein, we propose a transmucosal ocular delivery system of Posaconazole by developing a gellan gum–based in situ gelling nanosuspension. The HPLC method for Posaconazole was developed and validated as per ICH guidelines. The nanosuspension was prepared by microfluidization and optimized by Quality by Design. The gellan gum concentration selected was 0.4% w/v based on the viscosity and mucoadhesion measurements. A greater zone of inhibition of ~ 15 mm was observed for the prepared nanosuspension as compared to ~ 11 mm for the marketed itraconazole nanosuspension. A potential irritancy score of 0.85, considered to be non-irritant, was observed for the developed nanosuspension. Higher drug release of ~ 35% was noted for the nanosuspension compared to about ~ 10% for the coarse suspension. Ex vivo corneal retention studies on excised goat cornea demonstrated ~ 70% drug retention in the tissue. GRAPHICAL ABSTRACT: Graphical abstract depicting the central hypothesis of the work. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-022-01155-0.
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spelling pubmed-90892922022-05-10 Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole Khare, Purva Chogale, Manasi M. Kakade, Pratik Patravale, Vandana B. Drug Deliv Transl Res Original Article The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such drugs by increasing the contact time of the formulation. Herein, we propose a transmucosal ocular delivery system of Posaconazole by developing a gellan gum–based in situ gelling nanosuspension. The HPLC method for Posaconazole was developed and validated as per ICH guidelines. The nanosuspension was prepared by microfluidization and optimized by Quality by Design. The gellan gum concentration selected was 0.4% w/v based on the viscosity and mucoadhesion measurements. A greater zone of inhibition of ~ 15 mm was observed for the prepared nanosuspension as compared to ~ 11 mm for the marketed itraconazole nanosuspension. A potential irritancy score of 0.85, considered to be non-irritant, was observed for the developed nanosuspension. Higher drug release of ~ 35% was noted for the nanosuspension compared to about ~ 10% for the coarse suspension. Ex vivo corneal retention studies on excised goat cornea demonstrated ~ 70% drug retention in the tissue. GRAPHICAL ABSTRACT: Graphical abstract depicting the central hypothesis of the work. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-022-01155-0. Springer US 2022-05-10 2022 /pmc/articles/PMC9089292/ /pubmed/35538191 http://dx.doi.org/10.1007/s13346-022-01155-0 Text en © Controlled Release Society 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Khare, Purva
Chogale, Manasi M.
Kakade, Pratik
Patravale, Vandana B.
Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title_full Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title_fullStr Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title_full_unstemmed Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title_short Gellan gum–based in situ gelling ophthalmic nanosuspension of Posaconazole
title_sort gellan gum–based in situ gelling ophthalmic nanosuspension of posaconazole
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089292/
https://www.ncbi.nlm.nih.gov/pubmed/35538191
http://dx.doi.org/10.1007/s13346-022-01155-0
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