Investigation on the effect of deep eutectic formation on drug-polymer miscibility and skin permeability of rotigotine drug-in-adhesive patch.
Int J Pharm
; 574: 118852, 2020 Jan 25.
Article
en En
| MEDLINE
| ID: mdl-31759103
ABSTRACT
The aim of present study was to develop a rotigotine (ROT) transdermal patch by converting ROT to a form of deep eutectic 'liquid co-crystal'. Formulation factors including the type of ROT-organic acid deep eutectics, pressure sensitive adhesives (PSAs), drug-loading and patch thickness were investigated by in vitro skin permeation study and the optimized patch was evaluated by pharmacokinetics study. It was particularly concerned about the drug-polymer miscibility and skin permeability of ROT-lactic acid deep eutectics (ROT-LA). FTIR study, thermal analysis and molecular modeling were conducted to investigate the drug-PSA interaction. Multiple linear regression was performed to investigate the mechanism of the promoted skin permeability. The results showed that strong interaction was observed between ROT-LA and hydroxyl PSA, which inhibited the formation of ROT crystals. Skin permeability of ROT-organic acids deep eutectics were improved by the variations of apparent partition coefficient and glass transition temperature. AUC0-t and Cmax of optimized patch were 1290.6 ± 102.7 h ng/mL and 60.7 ± 12.0 ng/mL, respectively, which had no significant difference with commercial product. In conclusion, a reduced administration area (75%) and low risk of crystallization were introduced by the ROT deep eutectics, which demonstrated the feasibility of improving drug-polymer miscibility and skin permeability of transdermal drug.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polímeros
/
Piel
/
Tetrahidronaftalenos
/
Tiofenos
/
Adhesivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Pharm
Año:
2020
Tipo del documento:
Article
País de afiliación:
China