Development, Evaluation, and Molecular Docking of Oral Dissolving Film of Atenolol.

The development of oral dissolving film (ODF) of atenolol is an attempt to enhance convenience and compliance for geriatric patients suffering from hypertension. Film former is the most essential component in ODF that determines the physical characteristic and drug release. In this study, three different types of film former including HPMC E5 4% (w/v), 5% (w/v), CMC-Na 3% (w/v), 4% (w/v), and Na-alginate 2.5% (w/v), 3% (w/v) were optimized in Formula 1 (F1) to Formula 6 (F6), respectively. A solvent casting method was employed to develop ODF of atenolol. The films formed by HPMC E5 produced a smooth and flexible surface, whereas CMC-Na and Na-alginate produced gritty textured films. Satisfactory results were obtained from several physical parameters such as film thickness, folding endurance, swelling index, and disintegration time. The homogeneity, drug content, and dissolution properties of ODF with HPMC exhibited better characteristics than the other formulas. Formula 1 exhibited the highest drug release compared to the other ODFs. The molecular docking results showed that there was a hydrogen bonding between atenolol and film formers which was also supported by the FTIR spectrum. The findings of this study suggest that HPMC E5 is the most favorable film former for ODF of atenolol.

Multiple Functions of D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti-Ulcerative Colitis Analysis in Animal Model.

This study was conducted to evaluate the potential benefit of particle reduction down to nanoscale on curcumin, a unique natural active compound facing therapeutic problems due to low solubility and permeability. In addition, the presence of TPGS as a surfactant for multiple functions on curcumin nanoparticle was addressed. Observation was focused on bioavailability enhancement after oral administration and local anti-inflammatory improvement after rectal dosing. Nanonization of curcumin was performed using an up-scalable top down method. Specific animal models were used to study the in vivo kinetic profile and the biological activity of curcumin nanoparticle, compared with curcumin powder. d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticle was prepared through homogenization with high pressure of the 1500 bar. An in vivo study was performed after oral administration of the preparations to male healthy Wistar rats, to monitor the plasma kinetic profile of curcumin. The biological activity study was conducted after rectal administration of the preparations in Wistar rats induced by 2,4,6-trinitrobenzene sulfonic acid to develop ulcerative colitis. The curcumin nanoparticle with a size of approximately 200 nm was successfully produced and revealed a better in vivo kinetic profile over the larger size of curcumin mixed with TPGS, with bioavailability (AUC0-∞) that was accounted for seven-fold. In addition, the TPGS-stabilized curcumin nanoparticle demonstrated a superior local anti-inflammatory effect in ulcerative colitis, indicated by the shifting of observed parameters close to the healthy status. The tremendously improved anti-inflammatory effect of the TPGS-stabilized curcumin nanoparticle was found with a very low dose. Reducing the particle size of curcumin down to ~200 nm with the presence of TPGS seems to be a promising approach to improving the therapeutic value of curcumin.

TPGS-Stabilized Curcumin Nanoparticles Exhibit Superior Effect on Carrageenan-Induced Inflammation in Wistar Rat.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.