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This paper presents the development and validation of a new HPLC-UV method for simultaneous quantitative determination of clopidogrel and its hydrolysis product clopidogrel carboxylic acid (CCA) from bulk material and dosage formulations. Development of the chromatographic method is based on a design of experiments (DOE) approach. A Box-Behnken experimental design was used to build the mathematical models and to choose the significant parameters for the optimization by simultaneously taking resolution, capacity factor and peak symmetry as responses. Derringer's desirability function was used for the selection of the optimum experimental conditions in terms of mobile phase composition, column temperature and flow rate. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, robustness and system suitability. The method was further employed for the study of clopidogrel bisulfate hydrolysis kinetics under different pH conditions, with special emphasis on the acidic hydrolysis studies, since different clopidogrel salts are suffering pre-systemic metabolism trough hydrolysis under the acidic pH of the stomach. This effect is generally difficult to quantify, since CCA is also the main circulating metabolite, and no differentiation between the pre-systemic and systemic CCA can be made. In the acidic environment created by a 0.1N HCl solution CLO degradation was slow at room or body temperature (25 and 37°C respectively), less than 5% of the initial CLO amount being hydrolyzed after 48h. Under forced conditions (85ºC) however, 17.8% of CLO was transformed into CCA within 48 hours.

The present study was designed to evaluate the pharmacokinetic (PK) properties of di-μ-hydroxo-bis(quercetinatooxovanadium(IV) (HOBQOV) complex, with hypoglycemic and hypolipidemic properties, in rats after a single i.p. dose of 100 mg/kg b.w. The HOBQOV complex pharmacokinetics is described by a bicompartmental model and the plasma concentration decrease is described by two phases that might be correlated to the distribution and elimination processes. The obtained results suggest a PK profile of the complex suitable for a profound distribution in the animal organism with possibility of interaction with the cytosolic enzymes.

Nimesulide is a weakly acidic non-steroidal anti-inflammatory drug (NSAIDs). Like many non-steroidal anti-inflammatory drugs, Nimesulide is very sparingly soluble in water (≈ 0.01 mg/mL).The poor aqueous solubility and wettability of Nimesulide gives rise to difficulties in pharmaceutical formulations for oral or parenteral delivery, which may lead to variable bioavailability. Based on the Biopharmaceutical Classification System (BCS), Nimesulide is considered a BCS 2 drug (poorly soluble and highly permeable). Solubilization in surfactant solutions above critical micelle concentration (CMC) offers one approach to the formulation of poorly soluble drugs. Weakly acidic and basic drugs may be brought into solution by the solubilizing action of surfactants. In this study, different concentrations of Tween 80 was used in combination with buffer (pH 7.4) to increase the solubility of Nimesulide. The results show that the dependence of the released amount on the Tween concentration is not linear, very low Tween concentration showing a decrease of "solubility", probably connected to a critical micelle concentration at the interface Nimesulide solution. An "analytical" artefact connected to a decreasing ultraviolet absorption of Nimesulide because of Nimesulide precipitation, the formation of a colloidal solution is possible, and the phenomenon remains to be searched further. It is hard to explain that for an almost complete solubilization a significant Tween quantity is necessary and this should be more than that of other slightly soluble drugs.

This paper presents results of a pharmacokinetics study concerning pentoxifylline and its main metabolites after administration of extended release formulation of Trental 400 mg and correlation of this pharmacokinetics with in vitro dissolution test results of parent drug. In order to establish most relevant in vitro test, dissolution was performed in different experimental conditions (stirring rate and dissolution medium). Correlation was linear and very good. Generalization of correlation to rate of appearance of metabolites in plasma proved that this process could be well correlated with dissolution. Most relevant test was finally found to be the release in water medium, in conditions of a high stirring rate - 100 rpm.