A Combined In-Vitro and GastroPlus® Modeling to Study the Effect of Intestinal Precipitation on Cinnarizine Plasma Profile in a Fasted State.
AAPS PharmSciTech
; 24(5): 121, 2023 May 12.
Article
em En
| MEDLINE
| ID: mdl-37173520
ABSTRACT
Poorly water-soluble weak base molecules such as cinnarizine often exhibit pH-dependent solubility within the gastrointestinal tract. This means that their solubility can be influenced by the pH of the surrounding environment, and this can affect their oral absorption. The differential pH solubility between the fasted-state stomach and intestine is an important consideration when studying the oral absorption of cinnarizine. Cinnarizine has moderate permeability and is known to exhibit supersaturation and precipitation in fasted-state simulated intestinal fluid (FaSSIF), which can significantly impact its oral absorption. The present work is aimed at studying the precipitation behavior of cinnarizine in FaSSIF using biorelevant in vitro tools and GastroPlus® modeling, to identify the factors contributing to the observed variability in clinical plasma profiles. The study found that cinnarizine demonstrated variable precipitation rates under different bile salt concentrations, which could impact the concentration of the drug available for absorption. The results also showed that a precipitation-integrated modeling approach accurately predicted the mean plasma profiles from the clinical studies. The study concluded that intestinal precipitation may be one of the factors contributing to the observed variability in Cmax but not the AUC of cinnarizine. The study further suggests that the integration of experimental precipitation results representing a wider range of FaSSIF conditions would increase the probability of predicting some of the observed variability in clinical results. This is important for biopharmaceutics scientists, as it can help them evaluate the risk of in vivo precipitation impacting drug and/or drug product performance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cinarizina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
AAPS PharmSciTech
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos