The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.
Int J Pharm
; 547(1-2): 158-168, 2018 Aug 25.
Article
in En
| MEDLINE
| ID: mdl-29758344
ABSTRACT
Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients, or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations.
Key words
Full text:
1
Collection:
01-internacional
Topics:
Acesso_medicamentos_insumos_estrategicos
Health context:
1_ASSA2030
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Excipients
/
Intestinal Absorption
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Pharm
Year:
2018
Document type:
Article