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Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients

Dexamethasone, hydrochlorothiazide, spironolactone, and phenytoin are commonly used in neonates, but no age-appropriate formulation containing these active pharmaceutical ingredients (APIs) is commercially available. Thus, pharmaceutical compounding of the liquid oral dosage form is required to enab...

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Autores principales: Binson, Guillaume, Beuzit, Karine, Migeot, Virginie, Marco, Léa, Troussier, Barbara, Venisse, Nicolas, Dupuis, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523203/
https://www.ncbi.nlm.nih.gov/pubmed/31003500
http://dx.doi.org/10.3390/pharmaceutics11040190
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author Binson, Guillaume
Beuzit, Karine
Migeot, Virginie
Marco, Léa
Troussier, Barbara
Venisse, Nicolas
Dupuis, Antoine
author_facet Binson, Guillaume
Beuzit, Karine
Migeot, Virginie
Marco, Léa
Troussier, Barbara
Venisse, Nicolas
Dupuis, Antoine
author_sort Binson, Guillaume
collection PubMed
description Dexamethasone, hydrochlorothiazide, spironolactone, and phenytoin are commonly used in neonates, but no age-appropriate formulation containing these active pharmaceutical ingredients (APIs) is commercially available. Thus, pharmaceutical compounding of the liquid oral dosage form is required to enable newborn administration. A problem common to the compounded preparations described in the literature is that they include potentially harmful excipients (PHEs). Therefore, the aim of this study was to evaluate the feasibility of compounding oral liquid dosage forms free of PHE, containing dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone and to assess their physicochemical stability. Due to the poor water solubility of the targeted APIs, oral suspensions were compounded using Syrspend® SF-PH4 Dry, a suspending vehicle free of PHE. Four HPLC coupled to UV spectrometry (HPLC-UV) stability-indicating methods were developed and validated according to international guidelines to assay the strength of the targeted APIs. Whatever storage condition was used (5 ± 3 °C or 22 ± 4 °C), no significant degradation of API occurred in compounded oral suspensions. Overall, the results attest to the physical and chemical stability of the four oral liquid dosage forms over 60 days under regular storage temperatures. Finally, the use of the proposed oral suspensions provides a reliable solution to reduce the exposure of children to potentially harmful excipients.
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spelling pubmed-65232032019-06-04 Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients Binson, Guillaume Beuzit, Karine Migeot, Virginie Marco, Léa Troussier, Barbara Venisse, Nicolas Dupuis, Antoine Pharmaceutics Article Dexamethasone, hydrochlorothiazide, spironolactone, and phenytoin are commonly used in neonates, but no age-appropriate formulation containing these active pharmaceutical ingredients (APIs) is commercially available. Thus, pharmaceutical compounding of the liquid oral dosage form is required to enable newborn administration. A problem common to the compounded preparations described in the literature is that they include potentially harmful excipients (PHEs). Therefore, the aim of this study was to evaluate the feasibility of compounding oral liquid dosage forms free of PHE, containing dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone and to assess their physicochemical stability. Due to the poor water solubility of the targeted APIs, oral suspensions were compounded using Syrspend® SF-PH4 Dry, a suspending vehicle free of PHE. Four HPLC coupled to UV spectrometry (HPLC-UV) stability-indicating methods were developed and validated according to international guidelines to assay the strength of the targeted APIs. Whatever storage condition was used (5 ± 3 °C or 22 ± 4 °C), no significant degradation of API occurred in compounded oral suspensions. Overall, the results attest to the physical and chemical stability of the four oral liquid dosage forms over 60 days under regular storage temperatures. Finally, the use of the proposed oral suspensions provides a reliable solution to reduce the exposure of children to potentially harmful excipients. MDPI 2019-04-18 /pmc/articles/PMC6523203/ /pubmed/31003500 http://dx.doi.org/10.3390/pharmaceutics11040190 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Binson, Guillaume
Beuzit, Karine
Migeot, Virginie
Marco, Léa
Troussier, Barbara
Venisse, Nicolas
Dupuis, Antoine
Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title_full Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title_fullStr Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title_full_unstemmed Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title_short Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients
title_sort preparation and physicochemical stability of liquid oral dosage forms free of potentially harmful excipient designed for pediatric patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523203/
https://www.ncbi.nlm.nih.gov/pubmed/31003500
http://dx.doi.org/10.3390/pharmaceutics11040190
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