Yousry M. El-Sayed

Disposition of the Flavonoid Quercetin in Rats After Single Intravenous and Oral Doses

Abstract The pharmacokinetic and mean time tissue distribution parameters, after a single 50-mg/kg dose of quercetin administered as intravenous bolus, oral solution, and oral suspension, were determined using rat as an animal model. Following intravenous administration, the elimination rate constant and the elimination half-life were found to be 0.0062 min−1 and 111 min, respectively. Examining the mean time tissue distribution parameters reflected a strong binding affinity of the drug molecules to both plasma and tissue proteins. In addition, the low permeability rate of drug molecules in the peripheral system was demonstrated. Following the oral administration of the drug, the extent of absorption was greater from solution than from suspension. Moreover, the solution showed a shorter Tmax and a higher Cmax than suspension. The absolute bioavailability for the solution was 0.275 and that for suspension was 0.162. The mean residence time (MRT) and the mean absorption time (MAT) were higher for suspension, reflecting the need for dissolving the drug in order to be absorbed. The mean (in-vivo) dissolution time (MDTin-vivo) was 34.5 min. Thus, an oral quercetin formulation that can readily form a drug solution in the gastrointestinal tract may enhance the absorption of the drug.

In vivo evaluation of hydrochlorothiazide liquisolid tablets in beagle dogs

This study was carried out to evaluate the absorption characteristics of experimentally developed hydrochlorothiazide liquisolid tablets using six male beagle dogs. Comparison with reference commercial tablets was made. As no bibliographic data were found for the pharmacokinetic parameters of the drug in dogs, an intravenous drug administration was included in the study. The drug was administered orally as a single 25 mg dose of commercial and liquisolid tablets on two occasions in a randomized two-way crossover design. The pharmacokinetic parameters of the drug post intravenous dosing were reported for the first time. The results of the oral administration revealed statistically significant differences between the liquisolid and the commercial tablets in the area under the plasma concentration-time curve, the peak plasma concentration, and the absolute bioavailability. On the other hand, no significant differences were observed between the two formulations with regard to the mean residence time, the mean absorption time, and the rate of absorption. The absolute bioavailability of the drug from the liquisolid tablets was 15% higher than that from the commercial one. The parametric 90% confidence intervals for the different parameters were higher than the commonly expected intervals for bioequivalency, indicating greater bioavailability of the liquisolid tablets.

In vivo evaluation of sustained-release microspheres of metoclopramide hydrochloride in beagle dogs

The in vivo absorption characteristics of metoclopramide hydrochloride microspheres prepared from cellulose propionate polymer by an emulsion-solvent evaporation method were evaluated using six male beagle dogs. Metoclopramide was administered intravenously at a dose of 4 mg and orally as a single dose (10 mg) of microspheres and conventional tablets (Plasil®) on three separate occasions. Statistically significant differences were found between the two oral treatments in both the time and magnitude of the peak generated (p < 0.05). The absorption rate (Cmax/AUC) was significantly slower following the administration of microspheres. No significant difference was found between the two treatments in the area under the plasma concentration-time curve (AUC), indicating a comparable extent of absorption. The mean residence time (MRT) and mean absorption time (MAT) were dramatically increased following microsphere administration compared to the conventional tablets. The absolute bioavailability of metoclopramide from the microspheres and the conventional tablets was 72 and 65%, respectively. The in vivo results were found to be consistent with the in vitro availability of the drug.

Formulation and pharmacodynamic evaluation of captopril sustained release microparticles.

Cellulose propionate (CP) microparticles containing captopril (CAP) were prepared by solvent evaporation technique. The effects of polymer molecular weight, polymer composition and drug : polymer ratios on the particle size, flow properties, morphology, surface properties and release characteristics of the prepared captopril microparticles were examined. The anti-hypertensive effect of the selected CAP formulation in comparison with aqueous drug solution was also evaluated in vivo using hypertensive rats. The formulation containing drug : polymer blend ratio 1 : 1.5 (1 : 1 low : high molecular weight CP), namely F7, was chosen as the selected formulation with regard to the encapsulation efficiency (75.1%), flow properties (θ = 24°, Carr index = 5%, Hausner ratio = 1.1, packing rate = 0.535) and release characteristics. Initial burst effect was observed in the release profile of all examined formulations. DSC and SEM results indicated that the initial burst effect could be attributed to dissolution of CAP crystals present on the surface or embedded in the superficial layer of the matrix. The release kinetics of CAP from most microparticle formulations followed diffusion mechanism. After oral administration of the selected microparticle formulation (F7) to hypertensive rats, systolic blood pressure decreased gradually over 24 h compared to reference drug solution. These results may suggest the potential application of cellulose propionate microparticles as a suitable sustained release drug delivery system for captopril

Analysis of Prazosin in Plasma by High-Performance Liquid Chromatography Using Fluorescence Detection

Abstract A high-performance liquid chromatographic procedure using fluorescence detection has been developed for the determination of prazosin in plasma. Propyl-hydroxybenzoate was used as the internal standard. The chromatography was performed using adsorbsphere phenyl column; the mobile phase consisted of 30:70% acetonitrile to 0.05 M phosphate buffer and was adjusted to pH 3.3–3.4 using phosphoric acid; a flow rate of 1.5 ml/min; and the effluent was monitored at excitation and emission wavelengths of 247 and 394 nm, respectively. The retention times for prazosin and the internal standard were 4.0 and 6.0 min., respectively. The intraday coefficients of variation (CV) ranged from 1.15 to 4.96% at three different concentrations and the interday CVs varied from 0.05 to 8.99%. The mean (± SD) absolute and relative recovery of prazosin were found to be 97.4±3.14 and 100.68±2.19, respectively. Stability tests showed that prazosin is stable for at least 2 weeks in plasma after freezing. The minimum detectabl...

A Rapid and Sensitive High-Performance Liquid Chromatographic Method for the Determination of Metoclopramide in Plasma and Its Use In Pharmacokinetic Studies

Abstract A rapid and sensitive high-performance liquid chromatographic (HPLC) assay has been developed for the determination of metoclopramide in plasma. The assay is performed after single extraction of metoclopramide and diazepam (internal standard) from alkalinized plasma into ether and eluted from a Nova Pak C18-column with a mobile phase composed of acetonitrile:water (55:45%, v/v) adjusted to pH 3. The column eluent was monitored at 273 nm. Measurement was achieved by taking the peak-height ratios of the drug to the internal standard. The detection limit for metoclopramide in plasma is 5 ng/ml. Within-day coefficients of variation (CVs) ranged from 3.05 to 4.43% and between-day (CVs) from 4.1 to 5.7% at three different concentrations. Preliminary stability tests showed that metoclopramide is stable for at least 3 weeks in plasma after freezing. The method is applied for the determination of the pharmacokinetic parameters of metoclopramide after administration of two tablet formulations, to 4 healthy...

A Simple High-performance Liquid Chromatographic Assay for Sparfloxacin in Human Plasma

Abstract A simple, rapid and selective high-performance liquid chromatographic (HPLC) method for the determination of sparfloxacin in human plasma has been developed and evaluated. Plasma protein was precipitated with acetonitrile. The drug and the internal standard (furosemide) were eluted from a Nova Pak C18 cartridge column at 50°C with a mobile phase consisting of 5% acetic acid:acetonitrile:methanol (70:15:15% v/v). The column eluent was monitored at 364 nm. Each analysis required no longer than 5 min. Quantification was achieved by the measurement of the peak-area ratio of the analyte to the internal standard and the limit of quantification for sparfloxacin in plasma is 25 ng/ml. The intraday coefficient of variation (CV) ranged from 1.71% to 6.1%, and interday CV from 2.60% to 4.28% at four different concentrations. The absolute recoveries ranged from 98.6% to 104%, and the relative recoveries from 93.6% to 116.4% at four different concentrations. Preliminary stability tests showed that sparfloxaci...

High-performance liquid chromatographic analysis of indomethacin in serum.

A rapid high‐performance liquid chromatographic (HPLC) method for quantitative determination of indomethacin in serum is described. The assay was performed after single extraction of indomethacin and itraconazole (internal standard) from serum using diethyl ether and eluted from a 4 urn C‐18 reversed‐phase column at ambient temperature. The mobile phase consisted of ethanol:water:glacial acetic acid (65:34:1, v/v) pumped isocrati‐cally at a flow rate of l‐3ml/min. The effluent was monitored at 254 nm. Quantification was achieved by the measurement of the peak area ratio, and the absolute recoveries ranged from 94 to 97%. Within‐day coefficients of variation (CV) ranged from 2–72 to 5–70% and between‐day CV varied from 3–61 to 61%. Stability testing indicated that indomethacin is stable for at least 30 days in serum at – 20°C. The method was used to study indomethacin pharmacokinetics in rabbits.

High performance liquid chromatographic determination of ranitidine in human plasma

Abstract A rapid reversed phase HPLC method for determination of ranitidine in human plasma has been developed. The procedure involved extraction of the drug from alkalinized plasma spiked with the internal standard (procainamide) using 4% v/v isopropanol in ethylacetate. The extract was evaporated under nitrogen and the residue was reconstituted with methanol and injected onto U-Bondapak C18 column. The mobile phase is 8% v/v acetonitrile in 10 mM potassium phosphate buffer (pH 5.1); at a flow rate of 2.5 ml/min and UV detection at 330 nm. The efficiency of extraction was 90% with a detection limit of 20 ng/ml. The within-day coefficient of variations ranged from 4.09% to 5.81%, whereas those of between-day were from 7.5% to 9.51%.

Effect of food on bioavailability of bioadhesive-containing indomethacin tablets in dogs

Abstract The effect of food on the bioavailability of bioadhesive containing indomethacin tablets was evaluated on five male beagle dogs. Indomethacin was administered intravenously at a dose of 15 mg and orally in the fasting state and after food intake as a bioadhesive tablet at a dose of 25 mg. After dosing, serial blood samples were collected for a period of 6 h. Indomethacin plasma concentration was determined by a sensitive high-performance liquid Chromatographie assay. Food consumption dramatically reduced the area under the plasma concentration-time curve (AUC) and the maximum concentration (Cmax) by 86 and 76%, respectively. No significant differences were observed in the time to peak concentration (Tmax), mean residence time of the drug in the body (MRT), mean absorption time (MAT), elimination rate constant (Kel) and elimination half-life ( t 1 2 ) between the fasting and postprandial states. The mean gastrointestinal time (MGT) was found to be 0.81 h. The absolute bioavailability of the indomethacin bioadhesive tablets in the fasting state and after meal was 85.4 and 11.8%, respectively. Complexation of the bioadhesive material with the food contents is the most plausible explanation for the decrease in the extent of absorption of indomethacin.