Physicochemical stability of nefopam and nefopam/droperidol solutions in polypropylene syringes for intensive care units.

Introduction: Nefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow. Objectives: The first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours. Materials and methods: Three syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis. Results: Solutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20-25°C. No modification in visual or subvisual evaluation and pH values were observed. Conclusion: Nefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice.

Maltodextrin-modified graphene oxide for improved enantiomeric separation of six basic chiral drugs by open-tubular capillary electrochromatography.

An electrochromatographic capillary was modified with graphene oxide (GO), and the coating was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, and Fourier transform infrared spectra. By utilizing maltodextrin (MD) as the chiral selector, the basic chiral drugs nefopam (NEF), amlodipine (AML), citalopram hydrobromide (CIT), econazole (ECO), ketoconazole (KET) and cetirizine hydrochloride (CET) can be enantiomerically separated on this CEC. Compared with an uncoated silica capillary, the resolutions are markedly improved (AML: 0.32 → 1.45; ECO: 0.55 → 1.89; KET: 0.88 → 4.77; CET: 0.81 → 2.46; NEF: 1.46 → 2.83; CIT: 1.77 → 4.38). Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results. Graphical abstractSchematic representation of the preparation of graphene oxide-modified capillary (GO@capillary) for enantioseparation of drug enantiomers. The monolayered GO was used as the coating of the GO@capillary. Then the capillary was applied to construct capillary electrochromatography system with maltodextrin for separation of basic chiral drugs.

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

BACKGROUND: The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.