Cargando…
Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use
Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CE...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620304/ https://www.ncbi.nlm.nih.gov/pubmed/34834338 http://dx.doi.org/10.3390/pharmaceutics13111923 |
_version_ | 1784605188448845824 |
---|---|
author | Cirri, Marzia Mennini, Natascia Nerli, Giulia Rubia, Jessica Casalone, Enrico Melani, Fabrizio Maestrelli, Francesca Mura, Paola |
author_facet | Cirri, Marzia Mennini, Natascia Nerli, Giulia Rubia, Jessica Casalone, Enrico Melani, Fabrizio Maestrelli, Francesca Mura, Paola |
author_sort | Cirri, Marzia |
collection | PubMed |
description | Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and (1)H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test. |
format | Online Article Text |
id | pubmed-8620304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86203042021-11-27 Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use Cirri, Marzia Mennini, Natascia Nerli, Giulia Rubia, Jessica Casalone, Enrico Melani, Fabrizio Maestrelli, Francesca Mura, Paola Pharmaceutics Article Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage. The aim of this work was to develop an oral pediatric CEF solution endowed with good palatability, exploiting the solubilizing and taste-masking properties of cyclodextrins (CDs), joined to the use of amino acids as an auxiliary third component. Solubility studies indicated sulfobutylether-β-cyclodextrin (SBEβCD) and Histidine (His) as the most effective CD and amino acid, respectively, even though no synergistic effect on drug solubility improvement by their combined use was found. Molecular Dynamic and (1)H-NMR studies provided insight into the interactions of binary CEF:His and ternary CEF:His:SBEβCD systems used to prepare CEF solutions, which resulted stable and maintained unchanged antimicrobial activity during the two-weeks-use in therapy. The ternary solution was superior in terms of more tolerable pH (5.6 vs. 4.7) and better palatability, being resulted completely odorless by a panel test. MDPI 2021-11-13 /pmc/articles/PMC8620304/ /pubmed/34834338 http://dx.doi.org/10.3390/pharmaceutics13111923 Text en © 2021 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 Cirri, Marzia Mennini, Natascia Nerli, Giulia Rubia, Jessica Casalone, Enrico Melani, Fabrizio Maestrelli, Francesca Mura, Paola Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title | Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title_full | Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title_fullStr | Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title_full_unstemmed | Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title_short | Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use |
title_sort | combined use of cyclodextrins and amino acids for the development of cefixime oral solutions for pediatric use |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620304/ https://www.ncbi.nlm.nih.gov/pubmed/34834338 http://dx.doi.org/10.3390/pharmaceutics13111923 |
work_keys_str_mv | AT cirrimarzia combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT mennininatascia combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT nerligiulia combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT rubiajessica combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT casaloneenrico combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT melanifabrizio combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT maestrellifrancesca combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse AT murapaola combineduseofcyclodextrinsandaminoacidsforthedevelopmentofcefiximeoralsolutionsforpediatricuse |