Please provide a preparation for midazolam nasal administration.

Answer with the collaboration of Apoth. M. Dooms A useful composition is described In the January 2002 issue of the Pharmaceutical weekly magazine. Midazolam has in the group benzodiazepines a differentiated chemical structure. As the only benzodiazepine midazolam can form water-soluble salts and it has an increased stability in aqueous solutions. These properties were used in the formulation of the Midazolamneusspray. Midazolamhydrochloride is dissolved in a mixture of water and propylene glycol. The pH is 4.0. The final concentration of the nasal spray is determined at Midazolamhydrochloride 30.9 mg/ml. The used pump Atomizer provides an average volume of 90 μl determined at different filling degrees. As a base, 2.5 mg midazolam is delivered Per 90 μl of spray volume. The shelf life of two batches of nasal spray has been investigated using a stabilizing HPLC-UV method.

Compound of nasal spray with Midazolamhydrochloride 30.9 mg/ml

R/Midazolamhydrochloride 3.090 g Propylene glycol 25.90 g Benzyl alcohol 1.046 g Distilled water up to 100ml Preparation Add propylene glycol and benzyl alcohol to the largest portion of the distilled water and mix. Dissolve on midazolamhydrochloride. Fill to volume with distilled water.

Shelf Life The shelf life is six months at room temperature; provided protected from light. When stored at room temperature during the 6-month study period, no decomposition of midazolam in the nasal spray could be demonstrated. Longer preservation led to precipitation of presumably midazolam (?). Exposed to daylight, the solution colored yellow. By preserving the nasal spray in the dark, this could be prevented.

Directions Midazolamhydrochloride and benzyl alcohol are available from the Bassron Industries. Hopefully with an analysis protocol from an accredited laboratory. The amount of midazolamhydrochloride should be aligned with the spray volume of the pump atomizer. For this examination, a pump atomizer with a spray volume of 88.9 μl ± 3.4 μl is used. This is administered by spray 2.5 mg midazolam as a base. An important drawback of the solution is the complete and irreversible standstill of the vibration movement observed in the in vitro study. This indicates that the formulation is ciliotoxic. For use as an emergency medication, where the nasal spray is used only occasionally, ciliotoxicity may be a relative problem. The vibrhaarepial cells in the nasal mucosa are continuously replaced by new epithelial cells and thus the vibration function can be recovered after use of the nasal spray.