Stability of Drugs with Enteral Nutrient Formulas

Abstract

Experiments were performed to determine the chemical stability and compatibility of cephalexin, cimetidine, diazepam, or propranolol with full-strength and half-strength Isocal, Sustacal, and Sustacal HC (Mead Johnson). The enteral nutrient formulas (ENFs) containing the solid or liquid dosage forms were stored at 24°C and samples were taken at times 0, 1.5, 3, 6, 8, 10, and 24 hours. At each sampling time, the mixtures were visually examined for signs of incompatibilities such as precipitation, viscosity changes, and phase separation. Samples from each time period were analyzed by a stability-indicating high-performance liquid chromatography (HPLC) method. The drugs mixed with half-strength ENFs were also passed through ultrafiltration membranes to separate complexed from uncomplexed drug. Neither visual changes nor variations in pH were observed in any formula. With the exception of cephalexin suspension in half-strength ENFs, none of the drug concentrations changed appreciably throughout the study period. The assays performed for undecomposed drug at each sampling time for the various full- or half-strength ENF-solid drug mixtures stored at 24°C for 24 hours ranged from 92.3 to 103.4 percent for cephalexin, 96.2 to 103.0 percent for cimetidine, 93.9 to 106.2 percent for diazepam, and 95.5 to 102.2 percent for propranolol. For the liquid drugs, the concentration ranged from 86.5 to 102.1 percent for cephalexin, 97.0 to 101.1 percent for cimetidine, 98.2 to 103.0 percent for diazepam, and 97.4 to 104.8 percent for propranolol. Ultrafiltration studies showed varying percent binding dependent on the drug studied.