Effect of combined stabilizers on midazolam nanosuspension properties

Poorly soluble drugs are often a challenging problem in drug formulation. Midazolam is considered one of the best first-line drugs in managing status epilepticus in children who require emergency drug treatment. Owing to poor water solubility, however, oral bioavailability of midazolam is relatively low and insufficient. To improve its dissolution and absorption, nanosuspensions of midazolam hydrochloride were formulated with different stabilizers, such as Tween 80, Poloxamer 188, sodium carboxy methyl cellulose (NaCMC) and three-methyl chitosan (TMC) using the ultrasonic technique. The effects of combined stabilizers on nanosuspension physical properties such as particle size, zeta potential, viscosity and drug solubility were evaluated. The optimum midazolam nanosuspension containing 0.3% Poloxamer 188 and 0.3% TMC W/W had a mean particle size of 269 +/- 4 nm, zeta potential of 28.3 +/- 4 mV, viscosity of 23 MPa s and solubility of 398 mu g/mL. The freeze-dried powder of desirable midazolam nanosuspension was characterized by particle-size analyzer, SEM, stability test and dissolution test. Drug dissolution of the optimum midazolam nanosuspension was 1.8 times higher than that of the midazolam coarse suspension. The stability test showed that the midazolam nanosuspension was stable for 3 months. All results indicated that the nanosuspension of midazolam has proper properties for a new drug dosage form of midazolam with high oral bioavailability.

Automated summary

In this study, nanosuspensions of midazolam hydrochloride were formulated with different stabilizers to improve its dissolution and oral bioavailability. The optimum midazolam nanosuspension demonstrated proper physical properties and stability, showing potential for a new drug dosage form with high oral bioavailability.