Effect of common excipients on Caco-2 transport of low-permeability drugs

✍ Scribed by Bhagwant D. Rege; Lawrence X. Yu; Ajaz S. Hussain; James E. Polli

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 142 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1127

✦ Synopsis

The Biopharmaceutics Classi®cation System (BCS) allows waivers of in vivo bioequivalence for rapidly dissolving immediate-release (IR) formulations of drugs with high solubility and high permeability. One potential issue in possibly extending BCS biowaivers to low-permeability drugs is the potential for excipients to modulate the intestinal permeability of the drug. The objective of this work was to evaluate the effect of nine individual excipients on the Caco-2 permeability of seven lowpermeable compounds that differ in their physiochemical properties. Generally, most excipients had no in¯uence on drug permeability. With the exception of sodium lauryl sulfate, no excipient affected Caco-2 monolayer integrity. Sodium lauryl sulfate moderately increased the permeability of almost all the drugs. Tween 80 signi®cantly increased the apical-to-basolateral direction permeability of furosemide, cimetidine, and hydrochlorothiazide, presumably by inhibiting their active ef¯ux, without affecting mannitol permeability. Additionally, docusate sodium moderately increased cimetidine permeability. Other excipients did not have signi®cant effect on the permeability of these three drugs. Further work is needed to interpret the in vivo consequences of these observations from cell culture.