A new controlled-release liquid delivery system based on diclofenac potassium and low molecular weight chitosan complex solubilized in polysorbates.

A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24 h.

Azathioprine transport through rat skin and its immunosuppressive effect.

The objective of this research was to study the in vitro and in vivo percutaneous absorption of azathioprine with and without the effect of penetration enhancers. In vitro permeation of azathioprine was studied using a Franz diffusion cell and rat skin. Both azathioprine and 6-mercaptopurine were detected in the receiver solution with a reversed phase HPLC system. The steady state flux of azathioprine, permeability coefficient, and lag time were reported. Penetration enhancers such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), and urea were added to the donor compartment to increase the skin permeation of azathioprine. The flux of azathioprine was increased by 20.7%, and 22.4% using dimethylsulfoxide, and dimethylformamide respectively. The in vivo permeation was determined by measurement of antibody titers by the slide latex agglutination test. The in vivo permeation study showed that the titers of antibody induced in the rats were not affected by topical application of azathioprine solution. The results show that azathioprine has low flux to exert a systemic effect with and without penetration enhancers. However these results may support the use of topical azathioprine for the treatment of some dermatological disorders with minimum side effects.

Liquid chromatographic-mass spectrometric method for quantitative determination of lisinopril in human plasma.

A validated liquid chromatographic-mass spectrometric (LC/MS) method for the determination of lisinopril in human plasma is presented. Enalapril was used as an internal standard. After the addition of internal standard, solid phase extraction was used as a cleaning step. To separate lisinopril and enalapril from interfering endogenous plasma substances, the analysis was performed using column switching valve. The quantitative determination was performed using selected ion monitoring (+)-electrospray LC-MS. A combination of an acidic mobile phase and a reverse phase column was used. A precision in the linear range from 10 to 500.0 ng/mL plasma, absolute recovery of 91.69% for lisinopril and 90.26% for enalapril, stability for 3.5 months at -20 degrees C have been achieved. Limit of quantitation (LOQ) was 10 ng/mL while limit of detection (LOD) was about 1 ng/mL.

HPLC determination of naproxen in plasma.

An assay method using isocratic HPLC with fluorometric detection for the determination of naproxen sodium in plasma is presented. A reverse phase Microbondapack column was used with a mobile phase consisting of 42% acetonitrile and 58% water adjusted to pH 3 using phosphoric acid. The fluorometric detector with an excitation wavelength of 270 nm and emission wavelength of 340 nm provided high sensitivity and no interferences from plasma constituents. Plasma samples were injected to HPLC without any extraction. The method was precise and reproducible as was demonstrated by replicate analysis of pooled plasma sample containing 0.5-80 microg/ml naproxen sodium.

Chloramine-T in radiolabeling techniques. IV. Penta-O-acetyl-N-chloro-N-methylglucamine as an oxidizing agent in radiolabelling techniques.

Chloramine-T (CAT) is commonly used in radiolabeling of bioactive molecules by halogenation. CAT is used to release radioactive elemental iodine by oxidation of its salts. Unfortunately, CAT is a strong oxidizing agent and can cause significant damage to peptides and proteins. This may lower the yield of the iodination reaction and may produce undesirable side products. Recently, it was found that the in situ formation of N-chlorosecondary amines, by the addition of secondary amines to CAT prior to exposure to the substrate, can reduce the oxidative damage caused by CAT. To simplify the method, we prepared penta-O-acetyl-N-chloro-N-methylglucamine (NCMGE) as a solid N-chlorosecondary amine. The chemical reactivity of NCMGE toward a model amino acid, 1-aminocyclohexane carboxylic acid, was compared with that of chloramine-T. In the presence of the model amino acid, CAT lost all its chlorine titer within 60 min while NCMGE retained 99% of its chlorine titer. NCMGE was compared to CAT for the iodination of l-tyrosine and leucine enkephalin. For both substrates, the NCMGE method produced larger or equal yields of the monoiodo and diiodo products and less decomposition. It is proposed that the method employing NCMGE to release diatomic iodine is more convenient and efficient for radiolabeling peptides and proteins than currently used methods.