DARU, Journal of Pharmaceutical Sciences
Volume:9 Issue: 1, summer 2001

The electrophoretic mobility of three beta-blocker drugs, i.e. nadolol, oxprenolol and pindolol, in sodium acetate buffer containing different concentrations of methanol varying from 0 to 100 percent have been determined by a capillary electrophoresis instrument. The generated experimental data have been employed to evaluate the accuracy of a mathematical model to calculate the electrophoretic mobility at different concentrations of methanol. The proposed model is: In µm=¦c In µc+¦w In µw+K1 ¦c ¦w+K2 ¦²c ¦w. Where µ is the electrophoretic mobility, ¦ is the volume fraction, subscripts m, c and w are the mixed water-methanol, pure methanol and pure water, respectively, K1 and K2 are the model constants. The proposed model produced accurate results and the average percentage deviation between experimental and calculated mobilities was 1.21% for the data sets studied. This percentage error could be considered as an acceptable error where the relative standard deviation for the repeated experiments is around 2%.

A dynamic oscillatory technique was used to assess the effect of polysorbate non-ionic surfactants on mucus rheology. Adherent mucus gel was scraped from the surface mucosa of pig stomachs and purified by gel exclusion chromatography followed by ultrafiltration and gelation. Rheological measurements of this gel were carried out on a Carri-Med Controlled Stress Rheometer. Appropriate volumes of surfactant solution were added to weighed samples of mucus gel so that a final concentration of 20 mM surfactant was achieved in a gel containing 8% w/w solids content. Polysorbate 20 (PS20), polysorbate 40 (PS40), polysorbate 60 (PS60) and polysorbate 80 (PS80) all decreased both storage (elastic) modulus G’ and loss (viscous) modulus G’’ significantly at 10 Hz (P<0.05, ANOVA). The extent of rheological changes induced by the four polysorbates could be ranked as: PS80>PS20>PS60>PS40. The mechanisms by which surfactants disturb the mucus structure are not fully understood, nonetheless, they could possibly affect the mucus gel properties by causing depletion of the glycoprotein constituents such as non-mucin proteins and mucin associated lipids. This might lead to the conclusion that polysorbates, by reducing the viscoelasticity of mucus gel could alleviate its barrier properties and facilitate the diffusion of concomitantly administered drugs via mucus gel.

Physical characteristics of carbamazepine crystals grown from pure ethanol or acetone under different conditions were studied for the morphology of crystals by scanning electron microscope, x-ray powder diffraction and FT-IR, and for thermodynamic properties by differential scanning calorimeter. Also the dissolution behavior and compaction properties of crystals were studied. The results showed that crystallization of carbamazepine using watering-out method produced needle shape crystals while by the other methods such as reducing temperature or solvent evaporation produced polyhedral crystals in alcohol and thin plate-like crystals in acetone. The crystals which were grown from acetone were larger than those from alcohol. Differential scanning calorimetery and x-ray powder diffraction showed no evidence of poly-morphism for carbamazepine crystallized by reducing the temperature or by the solvent evaporation in contrast with the crystals produced by the watering out technique. Crystallization of carbamazepine by different methods especially watering-out technique improved its dissolution rate and compactibility and produced high crushing strength compacts without capping.

The bioequivalence of two preparations of enalapril maleate (20 mg tablets) manufactured in Iran has been exploited in reference to a standard preparation (Xanef 20 tablets, MSD, Germany) in 14 healthy volunteers. Following oral dosing of a single tablet of each of test and standard products, as a randomized crossover design with 10-day washout intervals, the blood samples were collected in predetermined time points and using a synthetic substrate, Hippuryl-Histidy-Leucine (HHL), the release of hippuric acid from the substrate was determined as Angiotensin-Converting-Enzyme (ACE) activity of serum fractions. The percent of ACE inhibition in each sample was calculated and plotted against time, from which three pharmacodynamic parameters, i.e. Emax, tmax and AUC0-24 were derived. The results of statistical comparison of these parameters showed that both of the test preparations are bioequivalent with reference standard preparation.