P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids.

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations' potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

Enhanced bioavailability and pharmacokinetics parameters of Enalapril solid self nanoemulsifying oral dispersible tablet: formulation, in vitro and in vivo evaluation.

Enalapril (EN) is an antihypertensive drug that is sparingly soluble in water with limited oral bioavailability. Successfully prepared self-nanoemulsifying systems (SNES) loaded with EN were developed. The solubility of EN in different oils, surfactants, and cosurfactants was tested. Pseudoternary phase diagrams were developed, and various SNES formulations were prepared and evaluated regarding content uniformity, emulsification time, droplet size (DS), and zeta potential (ZP). The selected system was examined using transmission electron microscopy. Solid Self-Nanoemulsifying Systems (SSNES) were formulated using Avicel® PH101 carrier and Aerosil® 200 adsorbent to form a free-flowing powder. The powder was formulated as an oral disintegrating tablet (ODT) using superdisintegrants and tested for physicochemical properties and stability. Finally, an in vivo pharmacokinetic study in healthy human volunteers was carried out. The composition of the selected SNES was 10% Labrafil®, 60% Tween 80, and 30% Transcutol® HP. It developed with an emulsification time of 21 sec, DP range of 60.16 nm, ZP of 1.17 mV, and spherical-shaped globules. The accelerated stability testing proved that there was no significant difference in physical properties after storage for 3 months. The percentage of relative bioavailability for formula F2 was 112.04%. The results of this study proved that the prepared EN-SSNES ODT represents a novel formulation alternative to the currently marketed tablet.

Silymarin loaded floating polymer(s) microspheres: characterization, in-vitro/in-vivo evaluation.

Silymarin has a short half-life (4-6 hours) which leads to necessity of frequent administration. Besides, it suffers from intestinal degradation. Thus, our study aims to formulate encapsulated floating microspheres using different polymers as HPMC, EC and a blend of them. Emulsion solvent evaporation technique was applied for preparation of microspheres. Parameters considered during preparation are drug: polymer ratio and emulsifier concentration. Selected formulations were characterized by SEM and subjected for assessment by drug entrapment efficiency, buoyancy for 12 hr, in- vitro drug release, kinetics of release and stability. In-vivo bio-equivalence study was performed using albino rabbits. Formula F24 (treatment II) exhibited high % buoyancy (73.4), higher t90 (190.7 day), high Cmax (1021.3 ng/ml) and Tmax (6 h) with a significant difference between it and treatment I (Silymarin plus) after carrying out ANOVA study. Also formula F24 exhibited MRT (hr) equal 9.44 ± 0.03 and high relative bioavailability RB% (227%), which indicates promising microspheres that could be used for effective management of liver disease.

Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium.

The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a non-steroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64-7.75) and gel strength (15.5-65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72-92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.

Pharmaceutical and pharmacokinetic evaluation of a novel fast dissolving film formulation of flupentixol dihydrochloride.

The objective of the present study was to develop fast dissolving oral film of the antipsychotic drug, flupentixol dihydrochloride, to enhance its bioavailability, optimize its therapeutic effect when used to treat depression with anxiety, and increase the convenience and compliance by the mentally ill, developmentally disable, elderly, and pediatric patients. Six formulae were prepared with different concentrations of water-soluble polymers vis. hydroxypropyl methylcellulose (HPMC E5) and carboxymethyl cellulose (CMC) by solvent casting technique. The prepared films were subjected to characterization for folding endurance, weight variations, thickness, disintegration time, drug release pattern, and drug content. Physical compatibility between the drug and excipients was guaranteed in the selected formulation (2% HPMC) by means of differential scanning calorimetry analysis and Fourier-transform infrared spectroscopy. This formulation revealed high stability after testing according to the International Conference on Harmonisation guidelines. In vivo studies based on single phase parallel design were carried out for the optimized formulation in healthy human volunteers. The concentration of flupentixol dihydrochloride in plasma samples was analyzed by a developed validated LC-MS/MS assay method and the pharmacokinetic parameters of the established formulation were compared with the commercially available oral tablets. Faster rate of absorption of flupentixol could be obtained from the oral film formulation and the relative bioavailability was found to be 151.06% compared to the marketed product.