Development of a Carvedilol Oral Liquid Formulation for Paediatric Use.
DoE
cardiovascular disease
carvedilol
liquid formulation
paediatrics
solubility
stability
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
05 Sep 2023
05 Sep 2023
Historique:
received:
20
07
2023
revised:
16
08
2023
accepted:
25
08
2023
medline:
28
9
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
Carvedilol (CARV) is an 'off-label' β-blocker drug to treat cardiovascular diseases in children. Since CARV is nearly insoluble in water, only CARV solid forms are commercialized. Usually, CARV tablets are manipulated to prepare an extemporaneous liquid formulation for children in hospitals. We studied CARV to improve its aqueous solubility and develop an oral solution. In this study, we assessed the solubility and preliminary stability of CARV in different pH media. Using malic acid as a solubility enhancer had satisfactory results. We studied the chemical, physical, and microbiological stability of 1 mg/mL CARV-malic acid solution. A design of experiment (DoE) was used to optimize the CARV solution's preparation parameters. A 1 mg/mL CARV solution containing malic acid was stable for up to 12 months at 25 °C and 30 °C and 6 months at 40 °C. An equation associating malic acid with CARV concentrations was obtained using DoE. Microbiological data showed that the use of methylparaben was not necessary for this period of time. We successfully developed an aqueous CARV solution suitable for paediatrics and proven to be stable over a 12-month period.
Identifiants
pubmed: 37765252
pii: pharmaceutics15092283
doi: 10.3390/pharmaceutics15092283
pmc: PMC10537783
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Generalitat de Catalunya
ID : CVE-DOGC-A-19269057-2019
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