DARU Journal of Pharmaceutical Sciences
Year:2001 | Volume:9 | Issue:1-2|Papers Count:9

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=f In µc+fw In µw+K1 fc fw+K2 f²c fw. Where µ is the electrophoretic mobility, f 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.

Liposomes have attracted much attention as a novel drug delivery system for controlled and/or targeted release of drugs. In reverse-phase evaporation, which is a well-known method of preparation for LUVs and SPLVs, the phospholipid concentration affects the preparation process, as well as characteristics of the resulting liposomes. Drug release rate from liposomes depends on permeability of the liposomal membranes. Cholesterol (CH) is quite often included in liposomal membranes to reduce their permeability to water-soluble molecules. In this study, the required concentration of the phospholipid Ovotin® 160 (O160) for the preparation of urea-containing stable plurilamellar vesicles, and the effect of different percentages of cholesterol on the encapsulation parameters and release rate of urea as a water-soluble model drug were investigated. The results show that there is a critical concentration of the phospholipid, under which the capability for the formation of a stable emulsion (in the emulsification part of the preparation process) sharply decreases. The release rate and encapsulation parameters increased when the molar ratio of cholesterol to O160 was 5% and decreased with the ratios of 50% and 100%. Therefore, in preparation of the optimum samples a balance between the encapsulation parameters as well as the release pattern should be considered carefully.

Preparation and characterization of nifedipine microspheres using ethylcellulose as matrix polymer is described. Nifedipine microspheres were prepared by solvent evaporation technique. The influence of different parameters such as the effect of the concentration of internal and external phases, the amount of drug and the rate of stirring of the medium on the size distribution of microspheres was studied. The effect of drug/polymer ratio and mean particle size on the drug release pattern was also evaluated. Drug release from nifedipine microspheres was studied in a medium, which simulated the change in pH of the pathway of the microspheres from stomach to intestine. It was found that with increase in the concentration of the internal phase, the size of microspheres became larger. Increasing the amount of polyvinyl alcohol in the external phase reduced the size of microspheres. Dissolution was found to be inversely related to the pH, in a way that drug release decreased at higher pH: Drug release from microspheres with small mean particle size was faster than those with large mesh particle size and followed Higuchi model of kinetics.

Black pepper has been used in traditional medicine as an analgesic. In this investigation, the effects of piperine, an alkaloid derived from black pepper seeds on the jumping induced by naloxone were studied on morphine dependent mice. This experimental study was conducted on case (piperine) and control (saline) groups of mice. Mice were made dependent to morphine using Marshall method. For evaluation of dependency, the number of jumps after naloxone injection was counted in a period of 30 minutes. There was a significant difference between number of jumps of mice in saline (10 ml/kg, IP) and drug groups (piperine 25, 50, 75 mg/kg, IP), as well as significant differences in latency period for jumping behavior in two groups. Based on these results, piperine may affect the intensity of morphine dependency.

The use of immunosuppressive medication such as Azathioprine, methoterxate and mercaptopurine in treatment of rheumatic disease in women at childbearing age has some risks of teratogeniesis. Cyclosporine is one of the newer medicines, which has been introduced for this disease but little is known about its teratogenicity. This study was designed to investigate the possible teratogenicity of this drug by using cultured rat limb bud cells, which were obtained from rat embryos 13 days after conception. Cells were incubated in trypsin-EDTA solution for 30 min at 37°C and then filtered through 50 µm nylon filters. The resultant cell suspension was cultivated in 1 ml Dulbecco modified Eagle medium (DMEM) containing 10% fetal bovine serum and 445 µg/L L-glutamine at 37°C with 5% CO2. After 8 days of culture the differentiated foci extract were measured by staining with 1% alcian blue. To assess the teratogenic effects of cyclosporine, it was placed in the culture well together with the cells. Results showed that the decrease in the expression of the extracellular matrix at dose of 0.01 molar of cyclosporine is due to limb bud cell toxicity rather than inhibition of cell differentiation.

The chemical composition of the essential oil of Phlomis olivieri Benth growing wild in Iran was examined by GC/MS. The oil contains over thirty-nine components. The major components are hexahydrofarnesyl acetone (13.3%), spathulenol (11.4%), germacrene-D (9.7%), β-caryophylene (6.9%) and caryophyllene oxide (5.3%). As a result of this investigation the oil of Ph.olivieri is characterized by a high content of sesquiterpenes and only trace amounts of monoterpenes.