Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.
Pharm Dev Technol
; 29(6): 639-647, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38980085
ABSTRACT
Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Administración Intranasal
/
Portadores de Fármacos
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Disponibilidad Biológica
/
Nanoestructuras
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Doxepina
/
Lípidos
Límite:
Animals
Idioma:
En
Revista:
Pharm Dev Technol
Asunto de la revista:
FARMACIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido