Critical dissolution tests of oral systems based on statistically designed experiments. II. In vitro optimization of screened variables on ER-coated spheres for the establishment of an in vitro/in vivo correlation.
Drug Dev Ind Pharm
; 24(3): 203-12, 1998 Mar.
Article
en En
| MEDLINE
| ID: mdl-9876576
ABSTRACT
The study was designed to optimize the effects of the screened in vitro dissolution variables agitation, temperature, osmolality, and polarity on the release of the neuroleptic compound remoxipride from extended release coated spheres. The variables were varied independently by means of a fractional factorial design. The in vitro tests were performed with the Basket method (USP). The polarity and the osmolality of the medium had significant effects on the dissolution rate of remoxipride. A statistical model was calculated based on the obtained dissolution in vitro. The model was then used to predict the in vitro conditions that most closely correlated with the dissolution rate of remoxipride in vivo, after administration of the formulation to 16 volunteers. The predicted in vitro conditions were experimentally verified, and an excellent association with the in vivo behavior of the formulation was found. Validation of the optimal in vitro conditions was performed on another batch of the formulation. The dissolution profile obtained showed a significant association with the corresponding dissolution profile in vivo. The use of statistically designed experiments in the development of critical dissolution tests for the establishment of in vitro/in vivo correlations seems to be a useful working approach, and supports further application to other oral solid systems.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preparaciones de Acción Retardada
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Drug Dev Ind Pharm
Año:
1998
Tipo del documento:
Article
País de afiliación:
Suecia