Assessment of Sorbitol as a Pharmaceutical Excipient in Oral Liquid Pediatric Formulations Submitted to the U.S. FDA.

Abstract

Sorbitol is a commonly used excipient in pediatric oral liquid formulations. Previous research revealed that sorbitol as an excipient can diminish the bioavailability of concomitant drugs. The reported cases and amount of sorbitol in pediatric formulations has not been explored, thus the aims of this study were to (1) examine the number of reports of sorbitol as an excipient in orally administered drugs with liquid formulations used in pediatrics, and (2) estimate the maximum amount of sorbitol that may be consumed per day for each drug. A compilation of drug products containing sorbitol as an excipient was retrieved from the Interagency Agreement between the National Institute of Child Health and Human Development (NICHD) and the Food and Drug Administration (FDA), and products with oral liquid formulations were selected. Maximum daily sorbitol amount was categorized into level 0 (< 3,200 mg), level 1 (3,200 mg to < 10,200 mg), level 2 (10,200 mg to < 13,400 mg), and level 3 (≥ 13,400 mg). Results indicated that sorbitol amount ranged between 0.06% and 45.7% weight to volume (w/v) across several therapeutic areas with the most prevalent being drugs intended for nervous system disorders. Corticosteroid drug products had the highest daily exposures to sorbitol, with amounts surpassing 45 grams. Percentages of products at levels 3, 2, 1 and 0 were 11.5%, 7.1%, 39.3%, and 42%, respectively. The potential impact of sorbitol content in pediatric formulations and the best practices for its use in pediatric polypharmacy needs to be further investigated.