Optimization, in-vitro Release and in-vivo Evaluation of Gliquidone Nanoparticles.

The present work embarks upon increasing the dissolution rate and the bioavailability of model anti-diabetic drug, gliquidone, a sulfonylurea class drug used for treating diabetes mellitus type 2. The gliquidone nanoparticles were prepared by using anti-solvent precipitation technique in which, gliquidone solution in acetone was added at a controlled rate to an aqueous solution containing polyvinylpyrrolidone K25 (PVP K25) as stabilizer. The effect of drug concentration (X1), polymer concentration (X2) and solvent to anti-solvent ratio (X3) on particle size and dissolution was studied using Box-Behnken design. The results revealed that by decreasing the drug concentration and by increasing the stabilizer concentration and solvent/anti-solvent ratio, reduction in the size of the particles was observed. The mentioned parameters were optimised and particle of size about 175 nm was achieved. The relative dissolution rate of prepared gliquidone nanoparticles in phosphate buffer pH 7.4 was ~ 4.7 times faster than original drug at t = 45 min. Further, the gliquidone nanoparticles were characterized by scanning electron microscope (SEM), Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). The particles revealed to be oval in shape with stabilizer molecules on surface and exhibited decreased crystalline nature when compared to free gliquidone. Finally, the in vivo studies using gliquidone nanoparticles revealed ~ 2.5-fold increase in Cmax when taken orally in the form of hard gelatin capsules in comparison to free gliquidone. Thus, overall investigation suggests that the developed strategy of gliquidone nanoparticles possess a keen potential for exhibiting anti-diabetic effect.

Formulation and Characterization of Nanosized Ethosomal Formulations of Antigout Model Drug (Febuxostat) Prepared by Cold Method: In Vitro/Ex Vivo and In Vivo Assessment.

Febuxostat (FXT) is a xanthine oxidase (XO) drug which indicated for the treatment of gout. FXT loaded nanosized ethosomes were prepared using cold method with varied concentrations of ethyl alcohol and soya lecithin (SL). The prepared ethosomes were characterized by size, entrapment efficiency (DEE), FT-IR, in vitro release, kinetic studies of in vitro release profile, in vitro skin permeation and deposition, and stability study. The selected ethosomal formulation was incorporated in HPMC gel and characterized for drug content, ex vivo diffusion study through rat skin, and in vivo study and determination of pharmacokinetic parameters using HPLC technique. The results of size analysis showed that minimum size was 124.2 ± 16.77 nm with PDI values between 0.2 and 0.6. The zeta potential was from - 43.5 ± 3.0 to - 20.6 ± 1.42 mV. DEE ranged from 48 to 86%. The results of in vitro skin permeation showed that the amount FXT permeated ranged from 43.33 ± 5.3 to 82.14 ± 5.8%, flux ranged from 14.85 to 28.02. The results of ex vivo study showed that the amount of FXT permeated from unprocessed FXT gel was 49.42 ± 3.29% which was lesser than from FXT ethosomal gel. The results of in vivo study showed that Cmax and tmax were significantly different and higher for transdermal administration of FXT than oral administration. The developed FXT nanosized selected ethosome-based transdermal drug delivery gel system would provide a promising method for better management of gout.

In vitro and in vivo characterization of fast dissolving tablets containing gliquidone-pluronic solid dispersion.

The main objective of this study is to increase the dissolution rate of gliquidone using its solid dispersions with pluronic F-68 by solvent evaporation method. The solid dispersion of the drug with pluronic at ratio 1:3 showed the highest dissolution efficiency (50.7%) after 10 min, so it was incorporated in fast dissolving tablets. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to study the interaction between gliquidone and pluronic in the solid state. The FTIR spectroscopic studies revealed no chemical interaction between the drug and pluronic, while the DSC results indicated the amorphous state of gliquidone in the solid dispersion. A 32 full factorial design was used to study the effect of varying concentrations of croscarmellose and sodium starch glycolate as superdisintegrants on the disintegration time and the percentage released after 10 min. The optimized formula showed a disintegration time of 39.1 ± 1.2 s and 85.43% ± 5.16% released after 10 min and was selected for the in-vivo studies in rabbits. The selected formula showed significant enhancement of gliquidone bioavailability, about 1.8 times compared with the commercial Glurenor tablets.

Utilizing mixer torque rheometer in the prediction of optimal wet massing parameters for pellet formulation by extrusion/spheronization.

In this study, we aimed to optimize theophylline pellet formulations using a two-factor three-level full-factorial design (32) by monitoring the concentration of two pellet excipients, polyvinyl pyrrolidone K30 (PVP) binder solution (X1) and the hydrophilic excipient mannitol (X2). Their impact on pellet characteristics (responses) were evaluated. Increasing PVP concentration in the binder solution resulted in an increase in the wet mass torque value. The effect of mannitol, however, was antagonistic. Moreover, the pellet particle size was significantly influenced by the level of mannitol, PVP solution, and quadratic effect of mannitol. Mannitol significantly antagonized the pellet particle size. Furthermore, increased mannitol concentrations significantly enhanced drug dissolution rate from the pellets, whereas PVP concentration in the binder solution significantly reduced the drug dissolution rate. In conclusion, wet granulations can be controlled by monitoring the composition of the binder solution and pellet composition.

Effect of Chemical Binding of Doxorubicin Hydrochloride to Gold Nanoparticles, Versus Electrostatic Adsorption, on the In Vitro Drug Release and Cytotoxicity to Breast Cancer Cells.

PURPOSE: The selective delivery of chemotherapeutic agent to the affected area is mainly dependent on the mode of drug loading within the delivery system. This study aims to compare the physical method to the chemical method on the efficiency of loading DOX.HCl to GNPs and the specific release of the loaded drug at certain tissue. METHOD: Bifunctional polyethylene glycol with two different functionalities, the alkanethiol and the carboxyl group terminals, was synthesized. Then, DOX·HCl was covalently linked via hydrazone bond, a pH sensitive bond, to the carboxyl functional group and the produced polymer was used to prepare drug functionalized nanoparticles. Another group of GNPs was coated with carboxyl containing polymer; loading the drug into this system by the means of electrostatic adsorption. Finally, the prepared system were characterized with respect to size, shape and drug release in acetate buffer pH 5 and PBS pH 7.4 Also, the effect of DOX.HCl loaded systems on cell viability was assessed using MCF-7 breast cancer cell line. RESULTS: The prepared nanoparticles were spherical in shape, small in size and monodisperse. The release rate of the chemically bound drug in the acidic pH was higher than the electrostatically adsorbed one. Moreover, both systems show little release at pH 7.4. Finally, cytotoxicity profiles against human breast adenocarcinoma cell line (MCF-7) exhibited greater cytotoxicity of the chemically bound drug over the electrostatically adsorbed one. CONCLUSION: Chemical binding of DOX·HCl to the carboxyl group of PEG coating GNPs selectively delivers high amount of drug to tumour-affected tissue which leads to reducing the unwanted effects of the drug in the non-affected ones.