Formulation and evaluation of antiviral drug sofosbuvir fast dissolving tablets using natural super disintegrants.

The main objective of this study to formulate of fast dissolving tablets of sofosbuvir, an antiviral drug used for hepatitis C virus. The direct compression method was employed for the formulation of sofosbuvir FDT and optimized for weight variation test, thickness, hardness, friability, wetting time, water absorption ratio, in-vitro disintegration test, and in-vitro dissolution studies, assay identification by using HPLC and stability studies. Master formulation of F4, Sofosbuvir showed promising results compared to others formulations and selected as the most suitable and best formulation among them. It also has better efficacy, disintegration and dissolution time. F4 was fabricated with both super disintegrants like croscarmellose sodium and sodium starch glycolate that lead to its required features. This formulation would be a good alternate for the management of viral diseases with better dissolution profile, stability and improved bioavailability for the patients.

Association of arsenic-related AS3MT gene and antioxidant SOD2 gene expression in industrial workers occupationally exposed to arsenic.

Increasing anthropogenic activities related to industrialization and exposure to different toxicants increases the health hazards of industrial workers. Arsenic (As) exposure induces DNA damage and generates reactive oxygen species, which may result in many disease phenotypes. Present study explores the expression variation of As 3 methyltransferase (AS3MT) and superoxide dismutase (SOD2) genes in blood samples of industrial workers of different industries (brick kiln, paint, welding, pesticide, and furniture) using quantitative real-time polymerase chain reaction. A total of 250 blood samples of industrial workers were collected along with age- and gender-matched controls. Relative expression of AS3MT (p < 0.05) and SOD2 (p < 0.01) genes was found significantly downregulated in exposed workers compared to controls. Significant low levels of AS3MT and SOD2 gene expression were observed in workers in the paint and pesticide industry compared to other industries. Similarly, reduced expression of AS3MT (p < 0.05) and SOD2 (p < 0.01) was observed in smokers of industrial workers compared to smokers of the control group. Workers with >10 years of exposure had less AS3MT expression compared to workers with <10 years of exposure. Additionally, a positive Spearman correlation was observed between AS3MT versus SOD2 (r = 0.742; p < 0.0001) in industrial workers. This study suggests that decreased AS3MT and SOD2 expression levels may lead to bioaccumulation of As in the body accompanied by increased oxidative stress ultimately inducing DNA damage.

Nano-sized Droplets of Self-Emulsifying System for Enhancing Oral Bioavailability of Chemotherapeutic Agent VP-16 in Rats: A Nano Lipid Carrier for BCS Class IV Drugs.

PURPOSE: The purpose of this study was to investigate the ability of a self-nano-emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of a BCS class IV drug, etoposide (VP-16). METHOD: A series of SNEDDS formulations with VP-16 were prepared consisting of medium chain triglycerides, polysorbate 80, diethylene glycol monoethyl ether and propylene glycol monolaurate type-1.  Based on an obtained ternary phase diagram, an optimum formulation was selected and characterized in terms of size, zeta potential, loading, morphology and in vitro drug release. The pharmacokinetic parameters and oral bioavailability of VP-16 suspension and VP-16 in SNEDDS was assessed using 30 Male Sprague-Dawley rats and compared with the commercial product (VePesid®). RESULTS: Pharmacokinetic data showed that the mean values for AUC0-t of VP-16 in SNEDDS was 6.4 fold higher compared to a drug suspension and 2.4-folds higher than VePesid®. Similarly, the mean value for Cmax of VP-16 in SNEDDS (1.13± 0.07 µg/ml µg.h/mL) was higher than VePesid® (0.62± 0.09 µg/mL) and drug suspension (0.13± 0.07 µg/mL). CONCLUSION: The SNEDDS formulation was able to enhance the oral bioavailability of the BCS Class IV chemotherapeutic agent VP-16 by increasing the dissolution and absorption of the drug. A good in vitro in vivo correlation was found between the in vitro dissolution and in vivo absorption data of VP-16 SNEDDS preparation. Therefore, SNEDDS formulations might be a very promising approach for BCS Class IV drugs.

A QUALITY BY DESIGN APPROACH: FABRICATION, CHARACTERIZATION AND EVALUATION OF OPTIMIZED TRANSDERMAL THERAPEUTIC SYSTEM FOR ANTIRHEUMATIC LORNOXICAM.

Microemulsion was prepared using several concentrations of selected oil (pine oil), surfactant (cre- mophor RH40), co-surfactant (isopropanol) and water to improve bioavailability by increasing solubility and permeability of lomoxicam, which was then incorporated to carbomer 940 gel base to fabricate microemulsion based gel (MEBG) to sustained permeability for transdermal delivery. Initially, the formulations were investi- gated for physicochemical characteristics, i.e., pH, conductivity, viscosity, refractive index, zeta size, poly-dis- persity index and Atomic Force Microscopy. Also, the significance of the components on in vitro permeability was observed to find out optimum microemulsion (ME,) using Box-Behnken-Design (BBD). MEBG was com- pared for in vitro permeation, stability, skin irritation and anti-inflammatory studies using control gel and in vivo bioavailability study with oral tablet. Microemulsions exhibited the physiological pH (5.35-5.99), oil in water nature (139-185 tsiemens/cm), isotropic (1.3390-1.4166), narrow size (62 nm), homogeneity, Newtonian flow (52-160 centipoise) and spherical shape. Predicted values (Q2, flux, lag time) of optimized microemulsions derived from BBD were in reasonable agreement with experimental values. The formulations were stable and non-irritating to the skin. Significant difference was investigated when comparing percent inhibition of edema of MEBG (80%) and control gel (40%) with respect to standard. The MEBG behavior differed significantly from oral tablet formulation in vivo bioavailability. Such BBD based estimation will reduce time and cost in drug designing, delivery and targeting.