Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling.
AAPS J
; 24(1): 17, 2022 01 04.
Article
em En
| MEDLINE
| ID: mdl-34982285
ABSTRACT
The present work aimed to differentiate between in vitro dissolution profiles of ibuprofen as input for GastroPlus™ and to see the impact on systemic exposure. In vitro dissolution profiles of ibuprofen obtained under low- and high-buffered dissolution media were used as input using the z-factor approach. In a second step, a customized surface pH calculator was applied to predict the surface pH of ibuprofen under these low- and high-buffered dissolution conditions. These surface pH values were adopted in GastroPlus™ and simulations were performed to predict the systemic outcome. Simulated data were compared with systemic data of ibuprofen obtained under fasted state conditions in healthy subjects. The slower dissolution rate observed when working under low-buffered conditions nicely matched with the slower dissolution rate as observed during the clinical aspiration study and was in line with the systemic exposure of the drug. Finally, a population simulation was performed to explore the impact of z-factor towards bioequivalence (BE) criteria (so-called safe space). Concerning future perspectives, the customized calculator should be developed in such a way to make it possible to predict the dissolution rate (being informed by the particle size distribution) which, in its turn, can be used as a surrogate to predict the USP2 dissolution curve. Subsequently, validation can be done by using this profile as input for PBPK platforms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
/
Ibuprofeno
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
AAPS J
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido