Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions.

Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions. Eur J Pharm Biopharm. 2019 Jul 12;: Authors: Roos C, Dahlgren D, Sjögren E, Sjöblom M, Hedeland M, Lennernäs H Abstract Oral administration of drug products is the preferred administration route. In recent decades there has been an increase in drug candidates with low solubility and/or low permeability. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed. These types of AMEs may also affect the regulatory assessment of a novel drug delivery system if they affect the absorption of a drug from any of the four BCS classes. The effects of AMEs have previously been investigated in various animal models, including the single-pass intestinal perfusion (SPIP) in rats. To further improve the biorelevance and the in vivo predictiveness of the SPIP model, four compounds (atenolol, enalaprilat, ketoprofen, metoprolol) were perfused in fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) together with the AMEs N-acetyl-cysteine, caprate, or sodium dodecyl sulfate. For the highly soluble and poorly permeating compounds enalaprilat and atenolol (BCS class III), the flux was increased the most by the addition of SDS in both FaSSIF and FeSSIF. For ketoprofen (BCS class II), the flux decreased in the presence of all AMEs ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research