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Pharm Dev Technol ; 29(8): 841-854, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39264666

RESUMO

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.


Assuntos
Administração Intranasal , Portadores de Fármacos , Lipídeos , Nanoestruturas , Sulpirida , Animais , Sulpirida/administração & dosagem , Sulpirida/farmacocinética , Sulpirida/farmacologia , Lipídeos/química , Portadores de Fármacos/química , Masculino , Nanoestruturas/química , Ratos , Tamanho da Partícula , Disponibilidade Biológica , Liberação Controlada de Fármacos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacocinética , Excipientes/química , Ratos Sprague-Dawley , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/efeitos dos fármacos
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