Midazolam structure is characterized by pH dependent ring opening phenomenon in which the ring remains open at pH values of less than 4, thus maintaining its water solubility.
The pK of midazolam is 6.15, which permits the preparations of salts to be water soluble. The parenteral solution of midazolam used clinically is buffered to an acidic pH of 3.5.
The solution of the midazolam structure contains 1 or 5 mg/mL midazolam plus 0.8% sodium chloride and 0.01% di-sodium-edetate, with 1% benzyl alcohol used as a preservative. It can be mixed with acidic salts of other drugs.
Midazolam injection is compatible and stable for 24 hours with 5% dextrose in water, and normal saline. The potency of midazolam decreases when mixed with lactated Ringer’s solution (or Hartmann’s solution) and should be used within 4 hours.
The ring closes at pH values of more than 4, as when the drug is exposed to the physiological pH, thus converting midazolam structure into a highly lipid soluble drug.