Effect of common excipients on intestinal drug absorption in Wistar rats

The aim of the present paper is to study the effect of common excipients on the permeability of atenolol (as drug absorbed mainly by passive diffusion) and rhodamine (as P-Glycoprotein substrate). Apparent permeability was measured by in situ perfusion method in Wistar rats using the Closed loop Doluisio’s Method. Permeability values were characterized in the absence and presence of 18 commonly used excipients. Excipient concentrations were selected based on the amounts in oral immediate release dosage forms, which failed the test during the human bioequivalence studies. Atenolol was studied with and without excipients in the whole small intestine, whereas, rhodamine was tested in three different intestinal segments to account for the differential expression of P-Glycoprotein and it was further on tested in the ileum, in the presence of excipients. Atenolol presented higher permeability values when it was administered with colloidal silica, croscarmellose, HPMC, magnesium stearate, MgCO3, PEG400, PVP, sorbitol, starch and TiO2 Rhodamine showed higher permeability values when it was administered with croscarmellose and HPMC. The mechanisms of action were not discernible with the proposed experiments. On the other hand, commercial formulations do not present a single excipient, but several which can counter-act their effects. The in situ perfusion technique can be useful for a preliminary screening and risk-analysis, while the in vivo pharmacokinetic results would be needed to define conclusive effects.

More on drug absorption and excipients

Alejandro Ruiz-PicazoAlejandro Ruiz-Picazo, Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche, Spain, More by Alejandro Ruiz-Picazo, Marta Gonzalez-Alvarez, Isabel Gonzalez-Alvarez, and Marival Bermejo, May 29, 2020, https://doi.org/10.1021/acs.molpharmaceut.0c00023