A Modern View of Excipient Effects on Bioequivalence: Case Study of Sorbitol

Abstract

As exemplified by sorbitol, some common excipients have unexpected effect on bioavailability/bioequivalence, depending on the pharmacokinetic characteristics of the drug, as well as the type and amount of the excipient present in the formulation. More research is warranted to examine other 'common' excipients that may have unintended influence on bioavailability/bioequivalence.

Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open‐Label, Randomized Study

“…Sorbitol had the greatest impact on lamivudine C max and AUC 0‐24 , and delayed t max , which suggests that sorbitol's effect was primarily on the absorption and bioavailability of lamivudine. These findings are consistent with the observed dose‐dependent effects of sugar alcohols on GI transit time and the PK parameters of low permeable drugs such as ranitidine and cimetidine 10, 14. For example, ranitidine t max was delayed, and a linear relationship was noted between the dose of sorbitol and ranitidine bioavailability, with 7.2%, 25%, and 45.5% reduction in ranitidine AUC, respectively, as the amount of sorbitol was increased from 1.25 to 2.5 to 5 g 10.…”

“…These findings are consistent with the observed dose‐dependent effects of sugar alcohols on GI transit time and the PK parameters of low permeable drugs such as ranitidine and cimetidine 10, 14. For example, ranitidine t max was delayed, and a linear relationship was noted between the dose of sorbitol and ranitidine bioavailability, with 7.2%, 25%, and 45.5% reduction in ranitidine AUC, respectively, as the amount of sorbitol was increased from 1.25 to 2.5 to 5 g 10. Sorbitol (5 g) had less effect on the higher permeability drugs metoprolol (17% reduction in bioavailability) and theophylline (no effect).…”

“…Interactions between sorbitol and active ingredients in medications have been reported in the literature 10. Like other nonabsorbed sugar alcohols, sorbitol increases osmotic pressure in the intestine, pulling water into the lumen and accelerating small intestine transit time.…”

“…Like other nonabsorbed sugar alcohols, sorbitol increases osmotic pressure in the intestine, pulling water into the lumen and accelerating small intestine transit time. This results in decreased absorption and bioavailability of low permeability drugs that are sensitive to changes in gastrointestinal (GI) motility and transit time 10, 11. Lamivudine is a highly soluble and well‐absorbed drug with an absolute bioavailability of 86% in adults5; however, there are conflicting reports as to whether lamivudine is a low or high permeability drug,12 with the results of an in vitro Caco‐2 study characterizing its permeability as moderate 13.…”

A Report from the Pediatric Formulations Task Force: Perspectives on the State of Child-Friendly Oral Dosage Forms

“…Clinical considerations may weigh against the use of nutritive sweeteners due to their cariogenic potential and comorbidity issues (e.g., diabetes). In addition, some nonabsorbable sweeteners (e.g., sugar alcohols) may increase intestinal motility and thus may adversely affect the absorption of some medications or cause diarrhea (29).…”