Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported. Those prodrugs showed a promising colorectal cancer chemopreventive activity. The current study aims to investigate the fate and hydrolysis of the prodrugs kinetically in different pH conditions, simulated gastric and intestinal fluids with pHs of 1.2, 5.5 and 7.4 in vitro at 37 °C. The effect of enzymes on the hydrolysis of prodrugs was also studied through incubation of these prodrugs at 37 °C in human plasma and rat liver homogenates. The pharmacokinetic parameters of selected prodrugs and the liberated nap were studied after oral and intraperitoneal administration in male wistar rats. The results showed the hydrolysis of naproxen amides of amino acid esters to nap through two steps first by degradation of the ester moiety to form the amide of nap with amino acid and the second was through the degradation of the amide link to liberate nap. The two reactions were followed and studied kinetically where K1 and K2 (rate constants of degradation) is reported. The hydrolysis of prodrugs was faster in liver homogenates than in plasma. The relative bioavailability of the liberated nap in vivo was higher in case of prodrug containing ethyl glycinate moiety than that occupied l-valine ethyl ester moiety. Each of nap. prodrugs containing ethyl glycinate and l-valine ethyl ester moieties appears promising in liberating nap, decreasing direct GI side effect and consequently their colorectal cancer chemopreventive activity.

Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported. Those prodrugs showed a promising colorectal cancer chemopreventive activity. The current study aims to investigate the fate and hydrolysis of the prodrugs kinetically in different pH conditions, simulated gastric and intestinal fluids with pHs of 1.2, 5.5 and 7.4 in vitro at 37 °C. The effect of enzymes on the hydrolysis of prodrugs was also studied through incubation of these prodrugs at 37 °C in human plasma and rat liver homogenates. The pharmacokinetic parameters of selected prodrugs and the liberated nap were studied after oral and intraperitoneal administration in male wistar rats. The results showed the hydrolysis of naproxen amides of amino acid esters to nap through two steps first by degradation of the ester moiety to form the amide of nap with amino acid and the second was through the degradation of the amide link to liberate nap. The two reactions were followed and studied kinetically where K1 and K2 (rate constants of degradation) is reported. The hydrolysis of prodrugs was faster in liver homogenates than in plasma. The relative bioavailability of the liberated nap in vivo was higher in case of prodrug containing ethyl glycinate moiety than that occupied l-valine ethyl ester moiety. Each of nap. prodrugs containing ethyl glycinate and l-valine ethyl ester moieties appears promising in liberating nap, decreasing direct GI side effect and consequently their colorectal cancer chemopreventive activity.

In this study, the oxidation of rabeprazole sodium (RAB Na+), a widely used anti-ulcer drug, was investigated at a modified poly (bromocresol green)/ pencil graphite electrode (poly (BCRG)/PGE). A disposable, sensitive and selective electrochemical platform is proposed for the determination of RAB Na+ by recording its cyclic voltammetry (CV) and square wave adsorptive voltammetry (SWV) in Britton-Robinson buffer solution at pH of 7.0 using the modified PGE. The poly BCRG/PGE displayed a good electrochemical behaviour with significant enhancement of the peak current compared to the bare PGE. Under experimental conditions, the modified electrode had a linear response range from 10-180 × 10-8 M and 3-330 × 10-7 M for SWV and CV, respectively. The detection limit was found to be 3 × 10-8 M and 1 × 10-7 M for SWV and CV, respectively. These voltammetric methods were successfully applied for the direct determination of RAB Na+ in real samples. The effect of various interfering substances on the RAB Na+ peak current was also investigated

In this study, the oxidation of rabeprazole sodium (RAB Na+), a widely used anti-ulcer drug, was investigated at a modified poly (bromocresol green)/ pencil graphite electrode (poly (BCRG)/PGE). A disposable, sensitive and selective electrochemical platform is proposed for the determination of RAB Na+ by recording its cyclic voltammetry (CV) and square wave adsorptive voltammetry (SWV) in Britton-Robinson buffer solution at pH of 7.0 using the modified PGE. The poly BCRG/PGE displayed a good electrochemical behaviour with significant enhancement of the peak current compared to the bare PGE. Under experimental conditions, the modified electrode had a linear response range from 10-180 × 10-8 M and 3-330 × 10-7 M for SWV and CV, respectively. The detection limit was found to be 3 × 10-8 M and 1 × 10-7 M for SWV and CV, respectively. These voltammetric methods were successfully applied for the direct determination of RAB Na+ in real samples. The effect of various interfering substances on the RAB Na+ peak current was also investigated

In this study, the oxidation of rabeprazole sodium (RAB Na+), a widely used anti-ulcer drug, was investigated at a modified poly (bromocresol green)/ pencil graphite electrode (poly (BCRG)/PGE). A disposable, sensitive and selective electrochemical platform is proposed for the determination of RAB Na+ by recording its cyclic voltammetry (CV) and square wave adsorptive voltammetry (SWV) in Britton-Robinson buffer solution at pH of 7.0 using the modified PGE. The poly BCRG/PGE displayed a good electrochemical behaviour with significant enhancement of the peak current compared to the bare PGE. Under experimental conditions, the modified electrode had a linear response range from 10-180 × 10-8 M and 3-330 × 10-7 M for SWV and CV, respectively. The detection limit was found to be 3 × 10-8 M and 1 × 10-7 M for SWV and CV, respectively. These voltammetric methods were successfully applied for the direct determination of RAB Na+ in real samples. The effect of various interfering substances on the RAB Na+ peak current was also investigated

The effect of adding surfactants to electrolyte containing rabeprazole sodium (RAB sodium) on its voltammetric response at pencil graphite electrode (PGE) was explored. The current signal due to the oxidation process as a function of the amount of the cited drug, pH of the medium, type of surfactant and accumulation time at the electrode surface was evaluated. The use of sodium dodecyl sulphate in the presence of Britton-Robinson buffer (pH=6.0) for the electrochemical determination of RAB sodium using cyclic voltammetry (CV) and Square wave adsorptive stripping voltammetry (SWAdSV) at PGE was studied. The oxidation peak current has varied linearly with the drug concentration over the range of 0.006-2.5×10-7 M and 0.5-250 μM using SWAdSV and CV, respectively. The limit of detection was found to be 0.2 nM and 0.18 μM using SWAdSV and CV, respectively. The validity of the proposed method for the determination of the studied drug in pure, pharmaceutical formulation in addition to urine was conducted.

The effect of adding surfactants to electrolyte containing rabeprazole sodium (RAB sodium) on its voltammetric response at pencil graphite electrode (PGE) was explored. The current signal due to the oxidation process as a function of the amount of the cited drug, pH of the medium, type of surfactant and accumulation time at the electrode surface was evaluated. The use of sodium dodecyl sulphate in the presence of Britton-Robinson buffer (pH=6.0) for the electrochemical determination of RAB sodium using cyclic voltammetry (CV) and Square wave adsorptive stripping voltammetry (SWAdSV) at PGE was studied. The oxidation peak current has varied linearly with the drug concentration over the range of 0.006-2.5×10-7 M and 0.5-250 μM using SWAdSV and CV, respectively. The limit of detection was found to be 0.2 nM and 0.18 μM using SWAdSV and CV, respectively. The validity of the proposed method for the determination of the studied drug in pure, pharmaceutical formulation in addition to urine was conducted.

The effect of adding surfactants to electrolyte containing rabeprazole sodium (RAB sodium) on its voltammetric response at pencil graphite electrode (PGE) was explored. The current signal due to the oxidation process as a function of the amount of the cited drug, pH of the medium, type of surfactant and accumulation time at the electrode surface was evaluated. The use of sodium dodecyl sulphate in the presence of Britton-Robinson buffer (pH=6.0) for the electrochemical determination of RAB sodium using cyclic voltammetry (CV) and Square wave adsorptive stripping voltammetry (SWAdSV) at PGE was studied. The oxidation peak current has varied linearly with the drug concentration over the range of 0.006-2.5×10-7 M and 0.5-250 μM using SWAdSV and CV, respectively. The limit of detection was found to be 0.2 nM and 0.18 μM using SWAdSV and CV, respectively. The validity of the proposed method for the determination of the studied drug in pure, pharmaceutical formulation in addition to urine was conducted.

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of less than 2 min. The emulsification efficiency was significantly superior at pH 6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90oC), ultrafine mean droplet size (12 ±1.4 to 24.5 ± 2.13 nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12 h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24 h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24 h with the maximum effect was observed after 2 h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of less than 2 min. The emulsification efficiency was significantly superior at pH 6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90oC), ultrafine mean droplet size (12 ±1.4 to 24.5 ± 2.13 nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12 h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24 h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24 h with the maximum effect was observed after 2 h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.