Pharmaceutica acta Helvetiae最新文献

A rapid, simple and sensitive high-performance liquid chromatographic method for the determination of captopril in plasma has been developed. Captopril is derivatized with a new reagent, 2-bromo-2′-acetonaphthone to form a product that showed ultraviolet-absorbing properties. For plasma samples, the protein was removed with 6% perchloric acid and the derivatized captopril was extracted with diethyl ether. The chromatographic separation was performed on an analytical μbondapak NH₂ column (300×3.9 mm, i.d) with an isocratic mobile phase consisting of n-hexane–2-propanol–methanol–acetic acid (68:15:15:2). Using ultraviolet detection at 246 nm, the quantification limit for captopril in plasma was 10 ng/ml. The calibration curve was linear over the concentration range 12.5–500 ng/ml. The average recovery was 95% for plasma. The inter-day and intra-day assay coefficients of variation were found to be less than 12%.

An automated system for the determination of fluoride in toothpaste, effluent streams, natural and borehole water based on the concept of flow injection with a fluoride-selective membrane electrode as sensor is described. The system is suitable for the on-line monitoring of fluoride at a sampling rate of 60 samples h⁻¹ in the linear range 10⁻⁴–10⁻¹ (approximately 1.9–1900 mg l⁻¹) with an RSD of better than 0.6%.

In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A₂ receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant Brazilian natural product, which occurs in Sassafras oil (Ocotea pretiosa). The results from preliminary evaluation of these novel aryl-sulfonamide compounds by the platelet aggregation inhibitory test, using rabbit PRP, induced by ADP, collagen, arachidonic acid, and U46619, identified the N-[2-(4-carboxymethoxyphenyl)ethyl]-6-methyl-3,4-methylenedioxyphenyl-sulfonamido derivative as the most active among them, presenting an IC₅₀ value for the U-46619-induced platelet aggregation in rabbit platelet-rich plasma: 329 μM.

A high glucose concentration has been found to lead to the glycosylation of amino groups of lysine residue in proteins. The addition of reducing agent not only prevents this reaction but also reverses it. On the other hand, flavonoids which found in plant sources have antioxidant properties. Since the glycosylation of protein is an oxidation reaction, therefore, antioxidants should be able to prevent this reaction. In this study, the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of flavonoids and their absence was measured by means of a colorimetric method. Different concentration of flavonoids (Quercetin, Rutin, Kaempferol) were used. The preventing effect on hemoglobin glycosylation by the three concentrations; 0.5, 5, 10 μg/ml was estimated as follows: for Rutin; 11%, 27%, 42%, Quercetin; 3%, 37%, 52%, Kaempferol; 10%, 12%, 15% respectively. So, the in vivo effect should be investigated and then plants that containing flavonoids can be utilized to prevent or treat complication of diabetes.

An attempt was made to improve the pharmacokinetic behaviour of 5-fluorouracil (5-FU) by incorporating it into lipoprotein imitating synthetic carrier `supramolecular biovector (SMBV)' which is an important prerequisite for achieving its better therapeutic performance against cancer. The polysaccharide core of SMBVs was prepared by ionotropic gelation technique by cross-linking polyguluronate units in the alginate molecules with calcium ions to form so called `egg-box structure'. The formulation and process variables were optimized to obtain particles of nanometer size range. Hydrophobization was carried out by fatty-acylation on the surface followed by phospholipid coating. Palmitoyl polyethylene glycol (p-PEG) was anchored to impart stealth behaviour. The scanning electron microscopy showed discrete spheres of average diameter 748 nm. Polydispersity was estimated to be 0.37. Overall zeta potential was −21.3 mV. The drug loading capacity and encapsulation efficiency was found to be 10.0% and 97.9%, respectively. The release from drug solution (AP) followed zero-order kinetics. Higuchi release pattern was obtained for egg-box complex cores (AP1) while first-order pattern was followed for fatty acylated (AP2) and lipid coated cores before (AP3) and after p-PEG anchoring (AP4). The amount of drug liberated in 24 h was in the order AP>AP1>AP2>AP4>AP3. The release pattern obtained was a combined effect of drug diffusion through egg-box matrix as well as partitioning in hydrophobic layer and p-PEG layer around the SMBV. The stability study showed negligible leakage and no appreciable change in particle size upon storage at different temperatures which is an indication of good stability of SMBV formulation. The plasma clearance data revealed increase in circulation half-life of drug and bioavailability. Tissue distribution data obtained was a result of competitive uptake of formulations from tissue macrophages and lymphatics depending upon its surface characteristics and residence period in vascular system. The enhanced delivery of drug to lymphatics and improvement in its half-life render SMBVs useful for control of metastasis and tumour growth.

The aim of the present study was to evaluate the influence of aluminium and iron on the in vitro dissolution kinetics of ciprofloxacin and ofloxacin as well as the usefulness of this type of in vitro data to predict modifications in in vivo absorption processes as a consequence of different factors, such as the widely documented in vivo interaction between quinolones and cations. Fitting of experimental data to different theoretical in vitro dissolution profiles was performed by non-linear regression methods and the statistical moments were calculated from raw experimental data. Analysis of residuals applied to dissolution curves as well as statistical comparison of the estimated parameters were carried out to evaluate the in vitro interaction. The results reveal significative modifications of the dissolution profiles of these quinolones as a consequence of the presence of cations, especially for Fe²⁺ which decreases 34.7% the maximum amount dissolved for ciprofloxacin and 29.1% for ofloxacin. Al³⁺ also produces a decrease of the total amount of quinolone dissolved although less relevant than Fe²⁺. Analysis of residuals proved to be the best statistical method to evaluate differences between whole dissolution profiles, at least under the experimental conditions used.

A new simple and accurate kinetic method for the analysis of paracetamol in pure form and formulations is described. The kinetics parameters have been applied successfully in determining paracetamol when it reacts with persulfate in alkaline medium. The spectrophotometric measurements have been recorded at 315 nm and found to be valid over the concentration range of 5–30 ppm. The molar absorptivity is equal to 6.55×10³ l mol⁻¹ cm⁻¹. The analysis of paracetamol content in mixture of different substances has been carried out without prior separation. The precision and accuracy of the method and the effect of foreign substances have been studied and the results obtained were compared with reference method.

Thebaine-derived μ-opioid agonists were synthesized through the reaction of thebaine with N-aryl maleimide and tested for opioid activity. Morphine was used as reference compound. Our results show that an attachment of aryl succinimide group to thebaine produced series of compounds with μ-opioid agonist activity. The most active compound in smooth muscle preparation was compound 6 with an IC₅₀ ratio of δ/μ=248.69 and was as potent as morphine with ED₅₀ value 26.65 mg kg⁻¹ i.p. in hot-plate test and showed good antinociceptive activity.

The pharmacokinetics of oxcarbazepine (30 mg kg⁻¹, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg⁻¹, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (C_max, T_max, t_1/2 and AUC_o–oo) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.