Physicochemical characterization of the metamorphosis of film-forming formulations of betamethasone-17-valerate.
Int J Pharm
; 664: 124595, 2024 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-39154921
ABSTRACT
Following topical application of a dermatological product, the loss (by evaporation and/or absorption through the skin) of volatile excipients will alter the composition of the formulation remaining on the tissue. This so-called metamorphosis impacts the concentration of the drug in the residual vehicle, (potentially) its physical form therein and, as a result, its uptake into and subsequent permeation through the skin. This research aimed to characterise - using primarily confocal Raman microspectroscopy - the metamorphosis of film-forming formulations of betamethasone-17-valerate (at different loadings) comprised of hydroxypropyl cellulose (film-forming agent), triethyl citrate (plasticizer) and ethanol (solvent). Dissolved and crystalline drug in the films were identified separately by their different characteristic Raman frequencies (1666 cm-1 and 1659 cm-1, respectively). These Raman measurements, as well as optical imaging, confirmed corticosteroid crystallisation in the residual films left after ethanol evaporation when drug concentration exceeded the saturation limit. In vitro release tests of either sprayed or pipette-deposited films into either aqueous or ethanolic receptor solutions revealed drug release kinetics dominated by the residual film post-metamorphosis. In particular, the rate and extent of drug release depends on the concentration of dissolved drug in the residual film, which is limited by drug saturation unless supersaturation occurs. For the simple films examined here, supersaturation was not detected and the solubility limit of drug in the films was sufficient to sustain drug release at a constant flux from the saturated films through a thin silicone elastomer membrane into an aqueous receptor solution for 30 h. Flux values were â¼ 1 µg cm-2h-1 from saturated residual films independent of the amount of crystallized drug present. Flux from subsaturated films was reduced by an amount that was consistent with the lower degree of saturation.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Espectrometría Raman
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Valerato de Betametasona
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Celulosa
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Etanol
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Liberación de Fármacos
Idioma:
En
Revista:
Int J Pharm
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos