Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration.

Midazolam is considered as one of the best first-line drugs in managing status epilepticus in children who require emergency drug treatment. Due to poor water solubility, oral bioavailability of midazolam is relatively low. To improve its dissolution and absorption, midazolam nano-suspensions were formulated with different stabilizers using the ultrasonic technique. A combination of Tween 80 and Poloxamer (TP) was considered as one stabilizer and 3-methyl chitosan (TMC) as another stabilizer. The ratio of the stabilizers was selected as an independent variable, and their effects on the particle size and the zeta potential were evaluated by the simplex lattice mixture method. The freeze-dried optimized midazolam nano-suspension powder was characterized by particle-size analysis, SEM, the stability test, and the dissolution test. The optimized midazolam nano-suspension (containing 76% TMC and 24% TP) had a mean particle size of 197 ± 7 nm and a zeta potential of 31 ± 4 (mV). The stability test showed that the midazolam nano-suspension is stable for 12 months. In the in vitro dissolution test, the midazolam nano-suspension showed a marked increase in the drug dissolution percentage versus coarse midazolam. In the in vivo evaluation, the midazolam nano-suspension exhibited a significant increase in the Cmax and the AUC0-5, and a major decrease in Tmax. The overall results indicate the nano-suspension of midazolam is a promising candidate for managing status epilepticus in children in emergency situation.

Preparation and in vitro evaluation of a new fentanyl patch based on functional and non-functional pressure sensitive adhesives.

In this study, some single-layer and double-layer transdermal drug delivery systems (TDDSs) with different functional and non-functional acrylic pressure-sensitive adhesives (PSAs) were prepared. For this purpose, fentanyl as a drug was used. The effects of PSAs type, single-layer and double-layer TDDSs on skin permeation and in vitro drug release from devices were evaluated using a hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices such as peel strength and tack values were obtained as well. It was found that TDDS with -COOH functional PSA showed the lowest steady-state flux. Double-layer TDDS displayed a constant flux up to 72 h. In double- and single-layer devices after 1 and 3 h, respectively, drug release followed Higuchi's kinetic model. Formulations with the highest percentage of -COOH functional PSA have displayed the lowest flux. The double-layer TDDSs with non-functional PSA demonstrated the suitable skin permeation rate close to Duragesic(R) TDDS and suitable adhesion properties.

Preparation and in vitro evaluation of a new fentanyl patch based on acrylic/silicone pressure-sensitive adhesive blends.

In this study, the influence of the ratio of silicone (Si) to acrylic pressure-sensitive adhesive (PSA), polyvinyl pyrrolidone (PVP), and lauryl alcohol (LA) % (wt/wt) on the properties of a drug in adhesive patch containing 4% (wt/wt) fentanyl as model drug was evaluated. The dependent variables selected were drug solubility, in vitro drug release in the platforms as well as adhesion properties including peel strength and tack value. By using the central composite design of Design Expert software, it was found that the effect of each factor was different, yet all had influenced dependent variables significantly (p < .05). Quadratic model generated for various response variables using backward regression analysis was found to be statistically significant (p < .05). It was deduced that the presence of PVP and Si displayed similar trends on drug solubility and release. Each role played by Si with LA and PVP in release rate was separately investigated, and it was found that the presence of PVP and LA in lowering the amount of drug released was more dominant compared with that of Si. The release patterns at the early and later stages follow the Higuchi and semiempirical models, respectively. Effect of PVP as well as Si and LA were similar on tack value. The influence of LA compared to peeling characteristics of Si system was more pronounced.