The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
Absorption modifiers
Bioequivalence
Intraintestinal administration
Permeation enhancers
Pharmaceutical development
Biofarmaci
Biopharmaceutics

Roos, CarlUppsala universitet,Institutionen för farmaci(Swepub:uu)carro115 (author)
Johansson, P (author)
Tannergren, C (author)
Lundqvist, A (author)
Langguth, P (author)
Sjöblom, Markus,1973-Uppsala universitet,Fysiologi(Swepub:uu)msj20812 (author)
Sjögren, Erik,1977-Uppsala universitet,Institutionen för farmaci(Swepub:uu)ersjo473 (author)
Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn (author)
Uppsala universitetInstitutionen för farmaci (creator_code:org_t)

In:International Journal of Pharmaceutics: Elsevier BV547:1-2, s. 158-1680378-51731873-3476

By the author/editor: Dahlgren, David; Roos, Carl; Johansson, P; Tannergren, C; Lundqvist, A; Langguth, P; show more...; Sjöblom, Markus, ...; Sjögren, Erik, 1 ...; Lennernäs, Hans; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

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