Question

Can the two drugs furosemide and midazolam be mixed in the same IV bag? explain the reasoning for your answer using chemical compatibility from molecular structure and an acid-base assessment.

Also, consider the bulkiness of both drugs and the fact that low molecular weight salts have better solubility.

Answer 1

Literature review revealed that furosemide-midazolam incompatibility is due to an acid–base reaction. In an equivolume (1:1) mixture, the formation of a visible milky-white precipitate is instantaneous. Because furosemide-midazolam incompatibility is pH-reliant, the impact of furosemide concentration is expected. Furosemide in 10 mg/mL of saline is an alkaline solution (pH = 8.77). Mixing a furosemide solution with an acidic solution (i.e., 5 mg/mL midazolam, pH = 3.47) decreases the pH of the mixture adequately to cause furosemide precipitation. Furosemide and midazolam concentrations were concurrently determined in the solution by UV spectrophotometry coupled with partial least square (PLS) regression to confirm this incompatibility. Even in the absence of visible particles, precipitation of furosemide led to a drug loss estimated at between 10% and 15%. Furosemide is more impacted by interaction because the pH of the mixture is acid and this form is poorly soluble in an aqueous solution. Physical incompatibility between furosemide and midazolam leads to a significant reduction in drug delivered to the patient and may result in treatment failure.

Furosemide has moleculer mass of 330 g/mol while midazolam has moleculer weight of 325 g/mol. Furosemide inhibits the metabolism of midazolam and enhance its excretion rate.

The larger the molecules of the solute are, the larger is their molecular weight and their size. It is more difficult it is for solvent molecules to surround bigger molecules. Therefore, smaller particles is usually more soluble. Both of these drugs are bulky, hence midazolam and furosemide have less solubility.