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.

Experimental design, formulation, and in-vivo evaluation of novel anticoagulant Rivaroxaban loaded cubosomes in rats model.

The aim of this study was to develop novel cubosomes as an oral delivery system to improve the permeation and anti-clotting activity of Rivaroxaban (RX). The experimental design (23 full factorial design) was employed to study individual and combined impacts of the assigned formulation variables. The variables RX amount (X1), Poloxamer (PX): GMO (GMO) ratio (X2) and PX/GMO: water ratio (X3) were taken as independent factors, and their effect was examined on entrapment efficiency (Y1), particle size (Y2), and zeta potential. (Y3). The cubosomal vesicle RX-C 3 composed of RX (20 mg), PX: GMO (1:0.5 % w/w), and PX/GMO: water (1:5% w/w) is the optimised formula achieving the required prerequisites. RX-C 3 had shown a vesicle size of 91.2 ± 1.3 nm, entrapment efficiency of 96.27 ± 0.12 %, and zeta potential of -24.1 ± 0.2 mV. The in-vivo studies showed revealed good inhibition of blood clotting, where RX-C 3 significantly increased clotting time by 35% and prothrombin time by 29% compared to Rivarospire®. In conclusion, the present study suggested that oral cubosomes formulations provide prolonged delivery of Rivaroxaban.

Intralesional vitamin D3 in treatment of alopecia areata: A randomized controlled clinical trial.

BACKGROUND: Alopecia areata (AA) is a common non-scarring, inflammatory type of hair loss that affects people of all ages and genders. AIMS: To evaluate the safety and efficacy of intralesional vitamin D3 injection in the treatment of alopecia areata. PATIENTS AND METHODS: A randomized controlled clinical trial included a total of 60 adult patients with localized alopecia areata were randomly assigned into two groups. Group I consisted of thirty patients who received 1ml of intralesional injection of vitamin D3 every 4 weeks for a maximum of 3 sessions. Group II consisted of thirty patients who received intralesional injection of normal saline 0.9% every 4 weeks for 3 sessions as a control group. All patients had their serum levels of 25-hydroxy vitamin D, TSH, antithyroglobulin, and thyroid peroxidase antibodies estimated before starting treatment. The 5-point semiquantitative regrowth score (RGS) and dermoscopy were used to evaluate the therapeutic response. RESULTS: There was statistically significant difference with p-value <0.001 between two study groups regarding degree of improvement. Dermoscopic findings that explain signs of activity were decreased, and signs of improvement were appeared after the third months of treatment being better in intralesional vitamin D group. The adverse effects were negligible and transient, and there was no recurrence of lesions. CONCLUSION: Intralesional vitamin D3 is an effective treatment option for localized patchy (not more than 40% of scalp distribution) alopecia areata. There is no relation between serum vitamin D3 and efficacy of treatment, so measuring vitamin D3 before starting treatment is not advised.

An overview on liquisolid technique: its development and applications.

With its simplicity and cost-effectiveness, the liquisolid technique offers solutions for numerous formulation problems. Among these are dissolution enhancement and sustaining drug release, and the liquisolid technique dealt with both approaches. This review focuses on the latest advances in the technique. It discusses modified additives for use as carrier materials, which secure the required large surface area for enclosing liquids. The review also covers the modern liquipellet technique derived from the extrusion/palletization technique. Also, the liquiground term is introduced, combining the advantages of co-grinding with the liquisolid concept. Furthermore, several grades of Eudragits, and hydrophilic retarding polymers are mentioned to explain modes of sustaining drug release. This review sums up the liquisolid technique development and its applications recently achieved.

What is this review about? This review is about a formulation technique known as 'liquisolid'. The article discusses the application of this technique in enhancing dissolution of water insoluble drugs and sustaining release of other drugs. It also complies the advances in this technique. How is the review structured? This review gives a highlight on the preparation of liquisolid compacts, the additives used formulation for both enhancing drug dissolution and drug release retardation. The review also includes sections for drug-release enhancement and the advances in this method as liquipellets and liquiground. There is also a section for utilizing this technique to sustain and control drug release. What can we conclude? In its simplicity of formulation, liquisolid techniques fits preparing solid dosage forms for a variety of release patterns.

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.