Micellar Liquid Chromatography Study of Quantitative Retention–Activity Relationships for Antihypertensive Drugs

Use of micellar mobile phases in reversed-phase liquid chromatography (RPLC) results in hydrophobic and electrostatic sites for interaction. Modified stationary phases in micellar liquid chromatography (MLC) are structurally similar to biomembranes. To confirm this we focused on the effects of the type and concentration of surfactant (Brij 35, SDS, and CTAB) and mobile phase pH on the retention of antihypertensive drugs on modified C₁₈ stationary phases. Quantitative retention-activity relationships are proposed for the drugs and the different surfactants and compared with those obtained using aqueous–organic mobile phases. Finally, a correlation was obtained between the logarithm of retention factors (log k) and the toxicity (LD₅₀) of antihypertensive drugs. Revised: 14 September 2005 and 4 April 2006     

Synthesis of cross-linked carboxymethyl cellulose and poly (2-acrylamido-2-methylpropane sulfonic acid) hydrogel for sustained drug release optimized by Box-Behnken Design

This research aims to fabricate and characterize chemically crosslinked CMC/PVP-co-poly (AMPS) based hydrogel for the sustained release of model drug metoprolol tartrate through the free radical polymerization technique. Box-Behnken Design was used to optimize CMC/PVP-co-poly (AMPS) hydrogel by varying the content of reactants such as; polymers (CMC and PVP), monomer (AMPS), and crosslinker (EGDMA). Carboxymethyl cellulose (CMC) was crosslinked chemically with AMPS with a constant ratio of PVP by the ethylene glycol dimethacrylate as the crosslinker in the presence of sodium hydrogen sulfite (SHS)/ammonium peroxodisulfate (APS) as initiators. After developing CMC-based hydrogels using different polymers, monomer, and crosslinker concentrations, this study encompassed dynamic swelling, sol–gel fraction, drug release and chemical characterizations such as FTIR, XRD, TGA, DSC, and SEM. In vitro drug release and swelling were performed at 1.2 and 6.8 pH to determine the sustained release pattern and pH-responsive behavior. These parameters depended on the crosslinker, polymer, and monomer ratios used in the formulation development. XRD, SEM, and FTIR showed the successful grafting of constituents resulting in the formation of a stable hydrogel. DSC and TGA confirmed the thermodynamic stability of the hydrogel. Hydrogel swelling was increased with an increase in the ratio of monomer; however, an increase in the ratio of polymer and crosslinker decreased the hydrogel swelling. In vitro gel fraction and drug release also depended on polymer, monomer, and crosslinker ratios. The fabricated CMC/PVP-co-poly (AMPS) hydrogels constituted a potential system for sustained drug delivery.     

Rutin as an Electrochemical Mediator in the Determination of Captopril using a Graphite Paste Electrode

A simple, rapid and sensitive cyclic voltammetry method is described for the determination of the antihypertensive drug captopril in aqueous solution using a graphite paste electrode with rutin as mediator. The catalytic role of rutin in the oxidation of captopril was confirmed by the increase observed in anodic peak current at+0.44 V vs. SCE in the presence of the mediator. Anodic peak current varied linearly with the concentration of captopril in the dynamic range 0.2 to 1.0 mmol L^?1. The method exhibited a limit of detection of 89.4 μmol L^?1 and a reproducibility of 1 %, values that are comparable with those exhibited by other methodologies employing electrodes without any modification. The recovery rate for the determination of captopril in a pharmaceutical sample was good (91.21 %) suggesting that the described analytical technique would be effective in industrial applications whilst offering a number of advantages over published cyclic voltammetric methods.     

Synthesis and reactions of thiosemicarbazides,triazoles, and <Emphasis Type="Italic">Schiff</Emphasis> bases as antihypertensive α-blocking agents

Methyl 2-(thiazol-2-ylcarbamoyl)acetate was synthesized and used as starting material. It was treated with hydrazine hydrate to afford the hydrazide, which was reacted with nitromethane and formaldehyde to give the saturated nitropyrimidine. The hydrazide was reacted with phenyl isothiocyanate to afford the thiosemicarbazide, which was cyclized with ethyl bromoacetate, sodium hydroxide, or sulfuric acid to afford N-phenylthiazolidinone, N-phenyltriazole, and thiadiazolyl derivatives. The methyl 2-(thiazol-2-ylcarbamoyl)acetate was coupled with diazonium salts of aniline, 4-chloroaniline, 4-bromoaniline, or 4-aminobenzenesulfonamide to afford the carbamoyl acetates, which were reacted with 2-aminobenzimidazole, 1,2,4,5-tetrachlorophthalic anhydride, and hydrazine hydrate to afford the corresponding thiazolylmalonamide, tetrachloroisoindolylimide, and tri-azole derivatives. Schiff bases and imides are newly synthesized candidates obtained via simple condensation of the hydrazide with aldehydes, 2,3-pyridinedicarboxylic anhydride, or 1,8-naphthalenedicarboxylic anhydride. The pharmacological screening showed that many of these compounds have good antihypertensive α-blocking activity and low toxicity. Correspondence: Abd El-Galil E. Amr, National Research Center, Applied Organic Chemistry, Dokki, Cairo, Egypt.     

Antihypertensive drugs as an inhibitors for corrosion of aluminum and aluminum silicon alloys in aqueous solutions

The corrosion behavior of aluminum and three aluminum–silicon alloys in different concentrations of HCl solutions and its inhibition by antihypertensive drugs was studied using potentiostatic polarization measurements. As the acid concentration increases, the rate of corrosion increases. Aluminum is less susceptible to corrosion than any of Al–Si alloys. The inhibition efficiency of the drug compounds increases with their concentration up to a critical value. At higher additive concentrations the inhibition efficiency starts to decrease. The inhibitive action of these compounds is due to their formation of insoluble complex adsorbed on the metal surface. The adsorption follows Langmuir adsorption isotherms. It was found that the drugs compounds provide protection to Al and Al–Si alloys against pitting corrosion by shifting the pitting potential to more positive direction until critical drug concentrations (250 ppm). After this critical concentration the inhibition against to pitting corrosion starts to decrease.     

Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs

The rigidity of nanoparticles was newly reported to influence their oral delivery. Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells. However, it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs. This study was for the first time to validate the semi-elastic core-shell poly(lactic-co-glycolic acid) (PLGA)-lipid nanoparticles (LNPs) as the carrier of the oral peptide drug. The antihypertensive peptide Val-Leu-Pro-Val-Pro (VP5) loaded LNPs (VP5-LNPs) were prepared by a modified thin-film ultrasonic dispersion method. Uptake experiment was performed in Caco-2 and HT-29 cells and monitored by high content screening (HCS) and flow cytometric (FCM). Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley (SD) rats and analyzed by DAS 2.0. The optimal VP5-LNPs had an average particle size of 247.3 ± 3.8 nm, zeta potential of −6.57 ± 0.45 mV and excellent entrapment efficiency (EE) of 89.88% ± 1.23%. Transmission electron microscope (TEM) and Differential scanning calorimeter (DSC) further confirmed the core-shell structure. VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h, indicating a great promotion of the oral bioavailability. The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.     

Quantitation of urapidil and its metabolites in human serum by high performance liquid chromatography

The antihypertensive agent urapidil (Ebrantil Byk-Gulden, Konstanz) can be reliably quantitated with three metabolites in human serum using high performance liquid chromatography. Serum is alkalinized and extracted with ethyl acetate. The organic phase is back-extracted with diluted acid. An aliquot is sampled automatically and chromatographed in an optimized combination of mobile and stationary phase. UV-detection at 273 nm allows a quantitation limit of 5 ng/ml for all analytes. Precise handling of exact volumes facilitates external calibration. The coefficient of variation for spiked samples is less than 5% within and less than 7% between studies. Application of the method to experimental and clinical pharmacokinetic studies of urapidil is illustrated.     

Synthesis and Spectral Characterization of Related Substances of Lacidipine,an Antihypertensive Drug

Five related substances (impurities) were detected in lacidipine bulk drug substance by a simple high-performance liquid chromatographic method (HPLC) and were identified by liquid chromatography–mass spectrometry (LC-MS). These related substances were independently synthesized, characterized, and co-injected with the sample containing impurities.