Ultrasound temporally increases skin permeability by altering stratum corneum SC function (sonophoresis). The objective of this study was to evaluate the effect of variable ultrasound conditions on the permeation of diclofenac sodium DS with range of physicochemical properties through EpiDerm™. Permeation studies were carried out in vitro using Franz diffusion cell. HPLC method was used for the determination of the concentration of diclofenac sodium in receiving compartment. Parameters like ultrasound frequency, application time, amplitude, and mode of sonication and distance of ultrasound horn from skin were investigated, and the conditions where the maximum enhancement rate obtained were determined. Application of ultrasound enhanced permeation of diclofenac sodium across EpiDerm™ by fivefolds. The most effective enhancing parameters were power sonication of 20kHz frequency, 20% amplitude at continuous mode for 5min.

Background: Transdermal drug delivery has many advantages compared to other routes. However, the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum and it was found that applying different ultrasound waves could enhance the skin's permeability.Objective: The aim of this work is to study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation.Method: The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method.Results: The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was also found upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane.Conclusion: Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions.

In this study analogues of compounds based on pyrano[2,3-d]pyrimidine were synthesized. 1,3-dimethyl-5- (thiomethyl)-2,4,7-trioxo-1,3,4,7-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carboxylic acid 3 and 1,3-dimethyl-5- (thiomethyl)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-trione 4 were obtained by the treatment of Triethylammonium 5- [(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(thiomethyl)methyl]-1,3-dimethylpyrimidine-2,4,6-trionate 1 with methyl sulfonic acid and pyridine, respectively. 5,5-dianilino-1,3-dimethyl-5,6-dihydro-2H-pyrano[2,3-d]pyrimidine- 2,4,7(1H,3H)-trione 6 was obtained after oxidizing compound 4 to produce 1,3-dimethyl-5-(methylsulfinyl)-2Hpyrano[ 2,3-d]pyrimidine-2,4,7(1H,3H)-trione 5 , then the sulfoxide group on compound 5 was replaced by aniline group.

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr^-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.