Nefopam hydrochloride compatibility and stability with selected proton pump inhibitors in bionolyte G5 injection for intravenous infusion

Abstract

The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. To assess the physical compatibility and the chemical stability of nefopam hydrochloride, a centrally acting non-opioid analgesic, when admixed with selected proton pump inhibitors (omeprazole, esomeprazole or pantoprazole), in bionolyte G5 injection for intravenous infusion. Admixtures were assessed for periods of up to 72 h after storage at ambient temperature without protection from light and at +4 degrees C protected from light. A preparation was considered stable if the compounds of the mixture retained at least 90% of their original potency during the storage. Triplicate samples of nefopam and the selected proton pump inhibitors as well as the following mixtures (nefopam/omeprazole, nefopam/esomeprazole and nefopam/pantoprazole) were prepared in the concentrations required, in polypropylene bottles of bionolyte G5 injection. The physical compatibility was assessed by visual observation at each sampling interval. The chemical stability of the drugs was evaluated by high-performance liquid chromatography and by measurement of pH values. During refrigerated storage, nefopam as well as the selected proton pump inhibitors, when prepared separately in bionolyte G5 injection maintained chemical stability for up to 7 days. At ambient storage conditions, the protons pump inhibitors maintained chemical stability for 24 h, but thereafter their concentrations decreased significantly at day 1. Nefopam maintained chemical stability for up to 72 h at +25 degrees C. Nefopam/omeprazole and nefopam/esomeprazole mixtures in bionolyte were physically incompatible with the mixtures exhibiting a black colour. They underwent rapid and extensive loss, making the combination unacceptable within minutes of mixing. However, the nefopam/pantoprazole mixture was compatible over the study period, but with a reduced duration of the stability. Within the limits defined above, nefopam and the selected proton pump inhibitors may be prepared separately in advance in bionolyte G5 injection. The nefopam/pantoprazole mixture was stable for a short period, while the nefopam/omeprazole and the nefopam/esomeprazole mixtures were incompatible and unusable, immediately upon admixture.