Reply to “On the Effect of Common Excipients on the Oral Absorption of Class 3 Drugs”

The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir

“…The observed results on bioaccessibility and intestinal permeability could also be important in the context of biowaiving. Based on human studies with acyclovir and cimetidine, Vaithianathan et al recently proposed widened biowaiver possibilities for changes in the content of 12 common excipients combined with BCS class III substances [37]. In the current case of potential excipient chitosan, the contrary can be concluded.…”

An Assessment of Occasional Bio-Inequivalence for BCS1 and BCS3 Drugs: What are the Underlying Reasons?

“…(1) targeted human studies on the effect of common excipients on BCS3 drugs 63,64 , ( 2) examples where absorption enhancing excipients have failed to improve human PK 65,66 (3) preclinical perfusion studies performed at relevant excipient and drug concentrations 67 (4) assessment of BE risks that have been performed with the theoretically high-risk BCS3 drug metformin 10 In addition they argue, the use of cell line data and even perfusion studies have many caveats regarding their use as predictive methods for excipient effects in humans 68,69 .…”

“…The modelling work by Yamane et al 35 highlights that the impact of sugar alcohol induced transit time may be increased for this category of drug. Even so, the robustness of the data for the failed BE study, which failed by a significant margin as reported by Garcia-Arieta et al 30 has been questioned by others, as the test product manufacturer subsequently managed to market a bioequivalent product containing the key excipient proposed to be altering permeation, sodium lauryl sulphate 64 .…”

Workshop Report: Implementation of Biowaivers based on the Biopharmaceutics Classification System

“…The results are described in the literature, including a reply to a letter to the editor from scientists from Spain, Canada, and Germany. (5,6) The studies presented measured the impact of 14 commonly used excipients on BCS class 3 drug absorption in humans. Cimetidine and acyclovir were used as model class 3 drugs across three separate BE studies in healthy human volunteers, denoted as study 1A, 1B, and 2.…”