Using Tiny-TIM Dissolution and In Silico Simulation to Accelerate Oral Product Development of a BCS Class II Compound.
AAPS PharmSciTech
; 23(6): 185, 2022 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-35778639
ABSTRACT
Though oral drug delivery is the most preferred route of administration, there is high drug pharmacokinetic variability associated with the oral route. Change in drug substance particle size distribution, formulation composition, or manufacturing process may impact the dissolution and, hence, the systemic drug absorption in biopharmaceutics classification system class II compounds. In the present research, using a Boehringer Ingelheim investigational drug substance as the model compound, the tiny-TIM in vitro data and in silico pharmacokinetic model were used to establish in vitro-in vivo correlation and to predict the oral bioavailability. The level C in vitro-in vivo correlation between in vivo AUC and in vitro amount dissolved in both fasted and fed states could be established. Furthermore, level A in vitro-in vivo correlation was established between in vivo fraction absorbed and bioaccessibility from tiny-TIM dissolution in both fasted and fed states. Prediction of positive food effect from tiny-TIM dissolution was consistent with conclusion from clinical studies. Such predictive models developed using the minimum clinical data and the in vitro tiny-TIM data have the potential to reduce the animal and human experiments and to expedite the overall drug development process.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biofarmácia
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
AAPS PharmSciTech
Ano de publicação:
2022
Tipo de documento:
Article