Mirtazapine loaded polymeric micelles for rapid release tablet: A novel formulation-In vitro and in vivo studies.

Major depression is a prevalent disorder characterized by sadness, lack of interest or pleasure, interrupted sleep or food, and impaired concentration. Mirtazapine (MTZ), a tetracyclic antidepressant drug, is commonly used to treat moderate to severe depression. MTZ is classified as a BCS class II drug that has shown bioavailability of 50% due to extensive first-pass metabolism. The aim of this research is to develop a delivery platform with enhanced solubility and oral bioavailability of MTZ through formulating polymeric micelles modeled in a rapid release tablet. Mirtazapine loaded polymeric micelles (MTZ-PMs) were formulated to enhance the solubility. Solutol® HS 15 and Brij 58 were used as combined surfactants in a ratio of (20:1) to MTZ in addition to Transcutol® P as a penetration enhancer. The following in vitro tests were performed: particle size, PDI, zeta potential, solubility factor, stability index, and transmission electron microscopes. Afterward, MTZ-PMs were converted to dry free flowable powder through loading on the adsorptive surface of Aerosil 200; then, the powder mixture was directly compressed (MTZ-PMs-RRT) into 13 mm tablets. MTZ-PMs-RRT was further investigated using in vitro evaluation tests of the tablets, namely, weight variation, thickness, diameter, hardness, friability, disintegration time, drug content, and in vitro dissolution test, which complied with the pharmacopeial limits. The pharmacokinetic parameters of MTZ-PMs-RRT compared to Remeron® tablet were further investigated in rabbits. The results showed enhanced solubility of MTZ with improved percentage relative bioavailability to 153%. The formulation of MTZ in the form of MTZ-PMs-RRT successfully improved the solubility, stability, and bioavailability of MTZ using a simple and scalable manufacturing process.

Chronological Delivery of Antihypertensive Drugs in Bilayered Core-in-Cup Buccoadhesive Tablets: In Vitro and In Vivo Evaluation.

Hypertension shows circadian blood pressure rhythms (day-night pattern) that urge the delivery of antihypertensive drugs at the right time in the desired levels. Thus, a bilayered core-in-cup buccoadhesive tablet was formulated that immediately releases olmesartan, to give a burst effect, and controls azelnidipine release, to prolong its therapeutic effect. The main challenge was the poor bioavailability of azelnidipine due to its poor aqueous solubility and first-pass effect. Hence, liquisolid compact buccoadhesive tablets were prepared to enhance solubility, dissolution profiles, and bypass the oral route. Two factorial designs were conducted to study the type and concentration effect of the mucoadhesive polymers on the dissolution and mucoadhesion of olmesartan and azelnidipine. Characterization studies were conducted regarding drug content, surface pH, water uptake, mucoadhesive strength, in vitro release, and ex vivo permeability. The core-in-cup olmesartan/azelnidipine buccoadhesive tablet showed similar release profile to the statistically optimized formulae of each drug. In vitro dissolution study showed enhanced release of azelnidipine than the directly compressed tablets, to comply with the regulatory standards of controlled release systems. In vivo pharmacokinetic study of olmesartan and azelnidipine conducted on human volunteers against Rezaltas® 10/8 mg tablet showed percentage relative bioavailability of 106.12 and 470.82%, respectively. Graphical Abstract.

Core-in-cup/liquisol dual tackling effect on azelnidipine buccoadhesive tablet micromeritics, in vitro release, and mucoadhesive strength.

Reduced bioavailability of azelnidipine is related to its poor aqueous solubility and extensive first-pass metabolism, which hinder its efficacy. These problems were addressed by implementing (1) a liquisol technique for promoting the dissolution rate in a controlled-release manner and (2) a core-in-cup bucco-adhesive drug delivery system as an alternative to the oral route. A 33 factorial design was used to study the effects of polymer type (sodium carboxymethyl cellulose (CMC Na), chitosan, or Carbomer P940) concentration (5, 10 or 15 %) and preparation technique (simple mix, liquisol or wet granulation) on the dissolution and mucoadhesion of core-in-cup azelnidipine buccoadhesive tablets. Tablet micromeritics, swelling index, mucoadhesive strength and in vitro release were characterized. Statistical analyses of these factors show ed significant effects on the studied responses, where F#16 prepared by the liquisol technique and containing 15 % CMC Na was chosen with an overall desirability of 0.953.