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Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameter...

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Autores principales: Afify, Enas A. M. R., Elsayed, Ibrahim, Gad, Mary K., Mohamed, Magdy I., Afify, Abd El-Moneim M. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798776/
https://www.ncbi.nlm.nih.gov/pubmed/29401498
http://dx.doi.org/10.1371/journal.pone.0191415
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author Afify, Enas A. M. R.
Elsayed, Ibrahim
Gad, Mary K.
Mohamed, Magdy I.
Afify, Abd El-Moneim M. R.
author_facet Afify, Enas A. M. R.
Elsayed, Ibrahim
Gad, Mary K.
Mohamed, Magdy I.
Afify, Abd El-Moneim M. R.
author_sort Afify, Enas A. M. R.
collection PubMed
description Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher C(max), [Image: see text] and [Image: see text] at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt(®). The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action.
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spelling pubmed-57987762018-02-23 Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures Afify, Enas A. M. R. Elsayed, Ibrahim Gad, Mary K. Mohamed, Magdy I. Afify, Abd El-Moneim M. R. PLoS One Research Article Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher C(max), [Image: see text] and [Image: see text] at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt(®). The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action. Public Library of Science 2018-02-05 /pmc/articles/PMC5798776/ /pubmed/29401498 http://dx.doi.org/10.1371/journal.pone.0191415 Text en © 2018 Afify et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Afify, Enas A. M. R.
Elsayed, Ibrahim
Gad, Mary K.
Mohamed, Magdy I.
Afify, Abd El-Moneim M. R.
Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title_full Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title_fullStr Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title_full_unstemmed Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title_short Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
title_sort enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798776/
https://www.ncbi.nlm.nih.gov/pubmed/29401498
http://dx.doi.org/10.1371/journal.pone.0191415
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