Statistical Design of Experiment (DoE) based development and optimization of DB213 in situ thermosensitive gel for intranasal delivery.
Int J Pharm
; 539(1-2): 50-57, 2018 Mar 25.
Article
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| MEDLINE
| ID: mdl-29366939
ABSTRACT
DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for the treatment of HIV-associated neurocognitive disorders. Current study aims to develop an in situ thermosensitive gelling system for intranasal delivery of DB213 facilitated by Statistical Design of Experiment (DoE) to conduct a more efficient experimentation by extracting the maximum amount of information from limited experiments. In our current study, information was extracted from twenty-five experimental designs from MODDE® Software and a mathematical model was successfully developed to predict formulations to achieve desired performance as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, Chitosan, DB213 and the performances of in situ thermosensitive gels. Based on DoE, in situ thermosensitive gels of 1% DB213 (F1) and 5% DB213 (F2) were developed for further in vivo bioavailability and brain uptake evaluations in Sprague-Dawley rats and C57BL/6 mice, respectively. In comparison to DB213 water solution, intranasal administrations of F1 at 1â¯mg/kg in rats and F2 at 25â¯mg/kg in mice demonstrated relative bioavailabilities of 145% and 165% with significant increase in brain uptake.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proyectos de Investigación
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Benzamidinas
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Modelos Estadísticos
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Composición de Medicamentos
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Geles
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Pharm
Año:
2018
Tipo del documento:
Article
País de afiliación:
Hong Kong