The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

Two new, simple, selective, and highly sensitive spectrofluorimetric methods were developed and validated for the determination of the antiepileptic drug; retigabine (RTG). The first method (Method-I) depends on enhancement of the weak native fluorescence of RTG via the use of an organized medium; sodium dodecyl sulphate (SDS) in acetate buffer (pH 3.74). The second method (Method-II) depends on the enhancement of RTG weak native fluorescence through complexation with a macromolecule; beta cyclodextrin (β-CD) in phosphate buffer (pH 3.20). A full study of different experimental parameters influencing the fluorescence intensity was carried out. In addition, a thorough investigation of the fluorescence quantum yield, fluorophore brightness and mechanism of fluorescence enhancement was performed. A seven-fold improvement in the fluorescence intensity was brought by the first method, whereas a six and half-fold enhancement of the fluorescence intensity was obtained by the second one. Linearity was achieved over wide ranges (0.05–12.5 μg mL−1) and (0.05–15 μg mL−1) with low limits of detection (LOD) of 10.6 and 14.3 ng mL−1, and limits of quantification (LOQ) of 32.0 and 43.2 ng mL−1 for (Method-I) and (Method-II), respectively. The proposed methods were validated according to ICH and US-FDA guidelines. The applicability of the proposed methods was tested for determination of RTG in its pharmaceutical dosage forms, and to study the stability of RTG under different stress conditions according to ICH guidelines including alkaline, acidic, oxidative, thermal, and photolytic stress conditions. Moreover, the high sensitivity achieved by the proposed methods permitted the determination and detection of RTG in both spiked and real rabbit plasma samples utilizing a simple protein precipitation step followed by liquid-liquid extraction method. Percentage recoveries from rabbit plasma samples were within the acceptable limits; (93.47–104.74%) and (91.33–105.70%) for (Method-I) and (Method-II), respectively.

Two new, simple, selective, and highly sensitive spectrofluorimetric methods were developed and validated for the determination of the antiepileptic drug; retigabine (RTG). The first method (Method-I) depends on enhancement of the weak native fluorescence of RTG via the use of an organized medium; sodium dodecyl sulphate (SDS) in acetate buffer (pH 3.74). The second method (Method-II) depends on the enhancement of RTG weak native fluorescence through complexation with a macromolecule; beta cyclodextrin (β-CD) in phosphate buffer (pH 3.20). A full study of different experimental parameters influencing the fluorescence intensity was carried out. In addition, a thorough investigation of the fluorescence quantum yield, fluorophore brightness and mechanism of fluorescence enhancement was performed. A seven-fold improvement in the fluorescence intensity was brought by the first method, whereas a six and half-fold enhancement of the fluorescence intensity was obtained by the second one. Linearity was achieved over wide ranges (0.05–12.5 μg mL−1) and (0.05–15 μg mL−1) with low limits of detection (LOD) of 10.6 and 14.3 ng mL−1, and limits of quantification (LOQ) of 32.0 and 43.2 ng mL−1 for (Method-I) and (Method-II), respectively. The proposed methods were validated according to ICH and US-FDA guidelines. The applicability of the proposed methods was tested for determination of RTG in its pharmaceutical dosage forms, and to study the stability of RTG under different stress conditions according to ICH guidelines including alkaline, acidic, oxidative, thermal, and photolytic stress conditions. Moreover, the high sensitivity achieved by the proposed methods permitted the determination and detection of RTG in both spiked and real rabbit plasma samples utilizing a simple protein precipitation step followed by liquid-liquid extraction method. Percentage recoveries from rabbit plasma samples were within the acceptable limits; (93.47–104.74%) and (91.33–105.70%) for (Method-I) and (Method-II), respectively.

Two new, simple, selective, and highly sensitive spectrofluorimetric methods were developed and validated for the determination of the antiepileptic drug; retigabine (RTG). The first method (Method-I) depends on enhancement of the weak native fluorescence of RTG via the use of an organized medium; sodium dodecyl sulphate (SDS) in acetate buffer (pH 3.74). The second method (Method-II) depends on the enhancement of RTG weak native fluorescence through complexation with a macromolecule; beta cyclodextrin (β-CD) in phosphate buffer (pH 3.20). A full study of different experimental parameters influencing the fluorescence intensity was carried out. In addition, a thorough investigation of the fluorescence quantum yield, fluorophore brightness and mechanism of fluorescence enhancement was performed. A seven-fold improvement in the fluorescence intensity was brought by the first method, whereas a six and half-fold enhancement of the fluorescence intensity was obtained by the second one. Linearity was achieved over wide ranges (0.05–12.5 μg mL−1) and (0.05–15 μg mL−1) with low limits of detection (LOD) of 10.6 and 14.3 ng mL−1, and limits of quantification (LOQ) of 32.0 and 43.2 ng mL−1 for (Method-I) and (Method-II), respectively. The proposed methods were validated according to ICH and US-FDA guidelines. The applicability of the proposed methods was tested for determination of RTG in its pharmaceutical dosage forms, and to study the stability of RTG under different stress conditions according to ICH guidelines including alkaline, acidic, oxidative, thermal, and photolytic stress conditions. Moreover, the high sensitivity achieved by the proposed methods permitted the determination and detection of RTG in both spiked and real rabbit plasma samples utilizing a simple protein precipitation step followed by liquid-liquid extraction method. Percentage recoveries from rabbit plasma samples were within the acceptable limits; (93.47–104.74%) and (91.33–105.70%) for (Method-I) and (Method-II), respectively.

Two new, simple, selective, and highly sensitive spectrofluorimetric methods were developed and validated for the determination of the antiepileptic drug; retigabine (RTG). The first method (Method-I) depends on enhancement of the weak native fluorescence of RTG via the use of an organized medium; sodium dodecyl sulphate (SDS) in acetate buffer (pH 3.74). The second method (Method-II) depends on the enhancement of RTG weak native fluorescence through complexation with a macromolecule; beta cyclodextrin (β-CD) in phosphate buffer (pH 3.20). A full study of different experimental parameters influencing the fluorescence intensity was carried out. In addition, a thorough investigation of the fluorescence quantum yield, fluorophore brightness and mechanism of fluorescence enhancement was performed. A seven-fold improvement in the fluorescence intensity was brought by the first method, whereas a six and half-fold enhancement of the fluorescence intensity was obtained by the second one. Linearity was achieved over wide ranges (0.05–12.5 μg mL−1) and (0.05–15 μg mL−1) with low limits of detection (LOD) of 10.6 and 14.3 ng mL−1, and limits of quantification (LOQ) of 32.0 and 43.2 ng mL−1 for (Method-I) and (Method-II), respectively. The proposed methods were validated according to ICH and US-FDA guidelines. The applicability of the proposed methods was tested for determination of RTG in its pharmaceutical dosage forms, and to study the stability of RTG under different stress conditions according to ICH guidelines including alkaline, acidic, oxidative, thermal, and photolytic stress conditions. Moreover, the high sensitivity achieved by the proposed methods permitted the determination and detection of RTG in both spiked and real rabbit plasma samples utilizing a simple protein precipitation step followed by liquid-liquid extraction method. Percentage recoveries from rabbit plasma samples were within the acceptable limits; (93.47–104.74%) and (91.33–105.70%) for (Method-I) and (Method-II), respectively.

Ionic liquid (IL)-type surfactants have been shown to interact more strongly with polar compounds thantraditionally used quaternary ammonium cationic surfactants. The aim of this study is to provide an alter-native micellar electrokinetic chromatographic method (MEKC) for the analysis of urinary nucleosides in their ionic form at low surfactant concentration. This approach could overcome the use of high surfactant concentrations typically associated with the analysis of these highly hydrophilic metabolites as neutral species, which is frequently accompanied by high electric current, Joule heating and long analysis time.The investigated IL-type surfactant; 1-tetradecyl-3-methylimidazolium bromide (C14MImBr) is similarto the commonly employed cationic surfactant; tetradecyltrimethyl ammonium bromide (TTAB) but it provides a different separation selectivity. We employed C14MImBr micelles for the MEKC analysis of seven urinary nucleosides. The studied analytes possess a negative charge at pH 9.38 (exceptions are adenosine and cytidine which are neutral at this pH value). Borate imparts an additional negative charge to these compounds after complexation with the cis-diol functionality of the ribose unit, which in turn enables them to interact with the oppositely charged C14MImBr micelles via electrostatic (Coulomb)forces. The effect of the concentration of borate (the complexing, competing and buffering ion) on the effective electrophoretic mobilities and on the retention factors was investigated. The effective elec-trophoretic mobility data show that complexation between these nucleosides and borate occurs withhigh degree of complexation even at very low borate concentration (2.5 mmol L−1 disodium tetraborate).In addition, we found that the retention factors are strongly dependent on the borate concentration being the highest when using the lowest borate concentration and they can be regulated by variation of either tetraborate concentration or the pH of the background electrolyte using only 20 mmol L−1 C14MImBr. We confirmed also that the main mode of interaction between these analytes and the C14MImBr micelles iselectrostatic interaction. Our experimental results reveal that the cationic surfactant C14MImBr exhibits superior selectivity and higher reproducibility relative to that of TTAB, which makes this surfactant a promising cationic surfactant for the MEKC separation of other hydrophilic polar analytes.

In respect to the major gastrointestinal disorders associated with oral administration of Lornoxicam, LOR, a potent anti-inflammatory drug, topical delivery could be an alternative route of administration. The objective of this work was to formulate LOR in the form of topical hydrogel after encapsulation into deformable vesicles, transfersomes, TRSs for maximum penetration and activity. LOR TRSs were prepared through thin film hydration technique and characterized for their encapsulation efficiency, size, charge, morphology and stability. Furthermore, LOR transfersomal and non-transfersomal hydrogels were prepared using different gelling agents and characterized for their pH, contents, viscosity, homogeneity, skin irritation, in vitro release, skin permeation, and pharmacodynamic activity. Results revealed that optimum LOR TRSs had an encapsulation efficiency of 99.34 ± 0.2%, size of 233.5 ± 12.5 nm and zeta potential of −35.34 ± 0.78 mV. Furthermore, they showed higher chemical and physical stability when stored in the fridge. Transfersomal hydrogels stabilized with sodium deoxycholate showed higher drug permeation through rat skin. In addition, they have higher flux and apparent permeability coefficient and superior anti-inflammatory activity compared to non-transfersomal LOR hydrogel and indomethacin gel as a standard NSAID. These findings confirmed that LOR transfersomal hydrogel is a promising topical formulation for effective treatment of local inflammatory conditions.