Vehicles for Drug Administration to Children: Results and Learnings from an In-Depth Screening of FDA-Recommended Liquids and Soft Foods for Product Quality Assessment

Abstract

Purpose Mixing with liquids or soft foods is a common procedure to improve acceptability of oral medicines in children but may affect drug stability and the in vivo performance of the administered drug product. The aim of the present study was to obtain an overview of the variability of critical attributes of commonly used vehicles and to identify which vehicle characteristics need to be considered when developing in vitro methods for evaluating product quality. Methods One product of each vehicle listed in the FDA draft guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration” was analyzed with regard to composition, calorific content and physicochemical properties. Results The studied vehicles show wide variability, both in composition and physicochemical properties. No correlation was observed between vehicle composition and physicochemical properties. Comparison of results of the present study with previously published data also provided variability in physicochemical properties within individual vehicle types. Conclusions To identify acceptable (qualified) vehicles for global drug product labeling, it is important that the vehicles selected for in vitro compatibility screening reflect the variability in composition and essential physicochemical properties of the vehicles recommended on the product label, rather than relying on results obtained with a single vehicle of each type. Future activities will focus on the development of standardized dosing vehicles that can represent key vehicle characteristics in all their variability to ensure reliable risk assessment.

Yoghurt as a deglutition aid for oral medication: effects on famotidine powder dissolution rate and pharmacokinetics

“…Famotidine is relatively susceptible to acid-catalysed hydrolysis and is degraded in HCl solutions 24 . Freeks et al 25 reported that famotidine inclusion using carboxyl-β-cyclodextrin improves the stability of famotidine under acidic conditions and the bioavailability of famotidine when orally administered to rats. It seems that deglutition foods might inhibit the degradation of famotidine mediated by gastric acid in vivo because of their effect on delaying famotidine dissolution.…”

Dispensing Oral Temozolomide in Children: Precision and Stability of a Novel and Ready to Use Liquid Formulation in Comparison with Capsule Derived Mixtures

“…The impact of mixing capsules, crushed tablets, and other oral compounded formulations with foods and beverages has been evaluated in some studies [ 25 , 26 , 27 , 28 ]. It was highlighted that the physicochemical properties of food vehicles are an important consideration for drug exposure [ 29 ].…”

“…This practice poses multiple risks, including exposure of the caregiver to a cytotoxic drug, imprecise delivery and dosing, partial drug intake if the food or beverage is not totally ingested or consumed, and uncontrolled stability of the active compound [ 8 , 15 , 20 ]. Here, we investigated the dosing accuracy and drug stability of TMZ in various food vehicles commonly used to aid administration to pediatric patients [ 18 , 29 ] and whether an investigational oral suspension of TMZ could offer improved dosage accuracy and stability.…”