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Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs

Intranasal administration is a promising route for brain drug delivery. However, it can be difficult to formulate drugs that have low water solubility into high strength intranasal solutions. Hence, the purpose of this work was to review the strategies that have been used to increase drug strength i...

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Autores principales: Pires, Patrícia C., Rodrigues, Márcio, Alves, Gilberto, Santos, Adriana O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955176/
https://www.ncbi.nlm.nih.gov/pubmed/35335964
http://dx.doi.org/10.3390/pharmaceutics14030588
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author Pires, Patrícia C.
Rodrigues, Márcio
Alves, Gilberto
Santos, Adriana O.
author_facet Pires, Patrícia C.
Rodrigues, Márcio
Alves, Gilberto
Santos, Adriana O.
author_sort Pires, Patrícia C.
collection PubMed
description Intranasal administration is a promising route for brain drug delivery. However, it can be difficult to formulate drugs that have low water solubility into high strength intranasal solutions. Hence, the purpose of this work was to review the strategies that have been used to increase drug strength in intranasal liquid formulations. Three main groups of strategies are: the use of solubilizers (change in pH, complexation and the use cosolvents/surfactants); incorporation of the drugs into a carrier nanosystem; modifications of the molecules themselves (use of salts or hydrophilic prodrugs). The use of high amounts of cosolvents and/or surfactants and pH decrease below 4 usually lead to local adverse effects, such as nasal and upper respiratory tract irritation. Cyclodextrins and (many) different carrier nanosystems, on the other hand, could be safer for intranasal administration at reasonably high concentrations, depending on selected excipients and their dose. While added attributes such as enhanced permeation, sustained delivery, or increased direct brain transport could be achieved, a great effort of optimization will be required. On the other hand, hydrophilic prodrugs, whether co-administered with a converting enzyme or not, can be used at very high concentrations, and have resulted in a fast prodrug to parent drug conversion and led to high brain drug levels. Nevertheless, the choice of which strategy to use will always depend on the characteristics of the drug and must be a case-by-case approach.
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spelling pubmed-89551762022-03-26 Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs Pires, Patrícia C. Rodrigues, Márcio Alves, Gilberto Santos, Adriana O. Pharmaceutics Review Intranasal administration is a promising route for brain drug delivery. However, it can be difficult to formulate drugs that have low water solubility into high strength intranasal solutions. Hence, the purpose of this work was to review the strategies that have been used to increase drug strength in intranasal liquid formulations. Three main groups of strategies are: the use of solubilizers (change in pH, complexation and the use cosolvents/surfactants); incorporation of the drugs into a carrier nanosystem; modifications of the molecules themselves (use of salts or hydrophilic prodrugs). The use of high amounts of cosolvents and/or surfactants and pH decrease below 4 usually lead to local adverse effects, such as nasal and upper respiratory tract irritation. Cyclodextrins and (many) different carrier nanosystems, on the other hand, could be safer for intranasal administration at reasonably high concentrations, depending on selected excipients and their dose. While added attributes such as enhanced permeation, sustained delivery, or increased direct brain transport could be achieved, a great effort of optimization will be required. On the other hand, hydrophilic prodrugs, whether co-administered with a converting enzyme or not, can be used at very high concentrations, and have resulted in a fast prodrug to parent drug conversion and led to high brain drug levels. Nevertheless, the choice of which strategy to use will always depend on the characteristics of the drug and must be a case-by-case approach. MDPI 2022-03-08 /pmc/articles/PMC8955176/ /pubmed/35335964 http://dx.doi.org/10.3390/pharmaceutics14030588 Text en © 2022 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 Review
Pires, Patrícia C.
Rodrigues, Márcio
Alves, Gilberto
Santos, Adriana O.
Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title_full Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title_fullStr Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title_full_unstemmed Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title_short Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs
title_sort strategies to improve drug strength in nasal preparations for brain delivery of low aqueous solubility drugs
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955176/
https://www.ncbi.nlm.nih.gov/pubmed/35335964
http://dx.doi.org/10.3390/pharmaceutics14030588
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