Compatibility of Oral Morphine Sulfate Solution with Enteral Feeding Products

Abstract

OBJECTIVE: Patients with terminal cancer often receive continuous enteral nutrition and oral medications concomitantly through nasogastric or gastrostomy feeding tubes. This study evaluated in vitro the compatibility of morphine sulfate (MS) solution 2 mg/mL (Roxane Laboratories) with three enteral nutrition products (Jevity [J], Osmolite-HN [O], and Pulmocare [P]) at 22 and 37 °C for 48 hours and J alone at 50 °C for 48 hours. METHODS: Mixtures containing 1 mg/mL MS were prepared with each enteral product: J, O, and P (Ross Laboratories). Serial samples (1 mL) were collected from each mixture and analyzed for morphine by reverse-phase HPLC. An analog pH meter was used to measure the pH of each mixture at scheduled intervals. RESULTS: The addition of MS 2 mg/mL (MS2) to J caused an immediate decrease in pH from 6.24 ± 0.01 to 4.96 ± 0.05 and a noticeable precipitate/phase separation. No phase separation was observed with a 1 mg/mL mixture of MS and J, O, and P when they were prepared with a more concentrated MS solution (20 mg/mL, MS20) (Roxanol Intensol). The pH declined linearly for all three enteral feeding products as the MS20 concentration was increased from 0 to 1 mg/mL. The precipitate observed in the mixture of MS2 with J was probably caused by the decrease in pH, which was caused by the greater volume fraction of MS solution. The concentration of morphine in the supernatant of a MS2/J solution was 0.83 mg/mL, and the concentration of MS in a homogeneous MS20/J solution was 0.86 mg/mL. At 48 hours, there was negligible (<2 percent) morphine decomposition in all MS admixtures at all temperatures. No microbial growth was observed in any admixture at 24 hours. Electrophoretic analysis demonstrated equal protein migration and molecular weight distribution for J and MS/J solutions. CONCLUSIONS: MS is stable in enteral feeding solutions at temperatures from 22 to 50 °C. MS2 is associated with a pH-dependent protein precipitation (but not destruction of the proteins), resulting in disproportionate concentrations of morphine in the supernatant and precipitate. This incompatibility may adversely affect enteral feeding analgesic delivery. We, therefore, recommend MS 20 mg/mL for this method of oral MS delivery, because of its superior compatibility and stability with enteral feeding products.