Iranian Journal of Pharmaceutical Research
Volume:1 Issue: 1, Autumn 2002

The pharmaceutical equivalency of both formulations was shown by in vitro characterization and dissolution testing. The comparative bioavailability of the two products was then determined in a single-blind, single dose, randomized, cross-over study in 14 healthy volunteers. A sensitive, rapid and precise high performance liquid chromatography (HPLC) method was used to measure concentrations of ranitidine in plasma samples collected up to 12 hours following each dose. Pharmacokinetic parameters, including Cmax, Tmax, AUC0-t, AUC0-¥, elimination rate constant (k) and half life were determined for both formulations. Analysis of the data revealed that the variations in all pharmacokinetic parameters were not statistically significant (p> 0.05), and the 90% confidence intervals for the test/reference mean ratios of the plasma pharmacokinetic variables lie within the conventional bioequivalence range of 80-125%. Therefore, both formulations were comparable based on the in vitro characterization and were bioequivalent in terms of Cmax and AUC.The two formulations were considered to be bioequivalent.

Mucosa-adhesive gels can be used as a useful mean of delivering drugs to or via mucosal membranes, and in particular buccal mucosa. Carbomers are among the best mucosa-adhesive materials known. The aim of this study was to compare the results obtained from the mucosa-adhesive strength of aqueous gels containing Carbomers, either alone or in combination, to the data obtained from assessing the duration of mucosa-adhesion of these gels. Based on initial studies, a total Carbomer concentration of 2.0%w/v forms the most desirable gel. Furthermore, it was found that gels containing a combination of Carbomers 934P (C934), 971P (C971) and 974P (C974) form clear and transparent gels with good spreadability. Next, using these Carbomers, gels containing either one, two or all three Carbomers with a total polymer concentration of 2.0%w/v were prepared and tested for their mucosa-adhesive strength to rat small intestine (as model mucosa) in pH6.8 isotonic phosphate buffer at 37 ºC. It was found that the presence of more than 0.4%w/v C971 in gels containing all three Carbomers, greatly reduce the mucosa-adhesive strength of the gel. Furthermore, it was found that a combination of C934 and C974 at a total concentration of 1.6-1.8%w/v, along with 0.2-0.4%w/v C971 form gels with good clarity and spreadability as well as strong mucosa-adhesive strengths. Gels showing the greatest mucosa-adhesive strength and good general appearance and spreadability were then assessed in terms of their duration of mucosa-adhesion to rat intestine in pH6.8 isotonic phosphate buffer at 37 ºC and under a constant applied force of 15.0g. The results obtained showed that a gel that has high mucosa-adhesive strength will not necessarily have a great duration of mucosa-adhesion. Hence, it is suggested that this important parameter should also be considered besides the test for assessing the mucosa-adhesive strength in the selection of an efficient transbuccal mucosa-adhesive drug delivery system.

Antimicrobial activity of different parts of Croccus sativus L. (saffron) including stigma, stamen, leaves and colora, extracted by various solvents, were tested against different bacteria (Microccucos luteus, Staphylococcus epidermitis, Staphylococcus aureus and E. coli) and fungi (Candida albicans, Aspergillus niger and Cladospourium sp) by cup plate diffusion method. Minimal Inhibitory Concentration (MIC) values of each active extract were determined. The results obtained show strong activity of the ethyl acetate extract of various plant parts of the plant (except leaves) against bacteria and fungi used as test organisms.

Drug therapy is a complex and important process and because of the importance of drug interactions, especially in in-patients, accompanying problems and obstacles would exist as a result of concomitant use of drugs in these patients. For this purpose 3130 prescription order forms from Bou-Ali hospital were collected and all potential drug interactions present were extracted and evaluated in terms of significance, severity, documentation and onset.Interactions were divided into 5 groups based on their significance, with group 1 being the most important and group 5 the least important.Most interactions observed belonged to groups 4 and 5, accounting for 68.5% of all interactions.Group 1 interactions only accounted for 7.8% of all interactions observed.When considering the onset of interactions, the most dominant type (55.8% of all interactions) were the slow-occurring ones. In terms of the severity, most interactions (47.2%) were of the medium (moderate) type. Strong (severe) interactions only accounted for 8.2% of all interactions.Finally, in terms of the documentation of interactions, the most prevalent type were the probable ones, accounting for 56.8% of all interactions observed. Definite interactions only accounted for 4.3% of all interactions..

The endogenous reactive oxygen species ("ROS") formation is associated with many pathologic states such as inflammatory diseases, neurodegenerative diseases, brain and heart ischemic injuries, cancer, and aging. The purpose of this study was to investigate the endogenous sources for "ROS" formation in intact isolated rat hepatocytes, in particular, peroxisomal oxidases, monoamine oxidase, xanthine oxidase, cytochrome P450, and mitochondria electron transport. The rat hepatocyte catalyzed oxidation of 2'',7''-dichlorofluorescin to form the fluorescent 2,7''-dichlorofluorescein was used to measure endogenous and xenobiotic-induced reactive oxygen species ("ROS") formation by intact isolated rat hepatocytes. Various oxidase substrates and inhibitors were then used to identify the intracellular oxidases responsible. Endogenous "ROS" formation was markedly increased in catalase inhibited or GSH depleted hepatocytes, and was inhibited by "ROS" scavengers or desferoxamine. Endogenous "ROS" formation was also inhibited by cytochrome P450 inhibitors, but was not affected by oxypurinol, a xanthine oxidase inhibitor. Mitochondrial respiratory chain inhibitors or hypoxia, on the other hand, markedly increased "ROS" before cytotoxicity ensued. This suggests endogenous "ROS" formation can largely be attributed to oxygen reduction by reduced mitochondrial electron transport components and reduced cytochrome P450 isozymes. Addition of monoamine oxidase substrates increased antimycin A-resistant respiration and "ROS" formation before cytotoxicity ensued. On the other hand peroxisomal substrates readily induced "ROS" formation and were cytotoxic towards catalase inhibited hepatocytes, which suggests that peroxisomal catalase removes endogenous H2O2 formed in the peroxisomes. The consequences of upregulation of peroxisomal oxidases are discussed.

Putative activity of hydroalcoholic and aqueous infusion extracts of Echium amoenum L. was investigated in mice using the rotarod model of motor coordination and the elevated plus maze model of anxiety. The extracts were administered intraperitonealy (i.p.) once, one hour before performing the tests. Preliminary phytochemical study of the plant, with standard procedures, showed that it contains saponins, flavonoids, unsaturated terpenoids and sterols. There was no evidence of tanins, alkaloids and cyanogenic glycosides. The hydroalcoholic extract of Echium amoenum in the dose range employed (125, 250 and 500 mg/kg) had no significant effect on motor coordination while the aqueous extract (62.5, 125, 250 and 500 mg/kg) disrupted motor coordination significantly. Intraperitoneal injection of aqueous extract (5, 10, 20, 30, 62.5, 80 and 125 mg/kg) showed a significant dose-dependent increase in time spent in open arm (OAT) with no significant change in open arm entries (OAE), closed arm entries (CAE) and total arm entries (TAE). The anxiolytic effect was most evident in 125 mg/kg group. It is almost evident that the extract produces its anxiolytic effect in the doses in which no change in motor activity is observable. Comparison of the dose response curve with the anxiolytic dose response of diazepam (0.25, 0.5, 1.0 and 2.0 mg/kg) in the same setting showed that the maximal efficacy of the extract is significantly lower than diazepam. Because of different maximal efficacies we were not able to calculate Extract/diazepam potency ratio but it does not seem to be more than 1/100. It is concluded that single administration of aqueous extract of Echium amoenum L. produces a significant but mild to moderate anxiolytic effect.

Antimicrobial activity of different parts of Croccus sativus L. (saffron) including stigma, stamen, leaves and colora, extracted by various solvents, were tested against different bacteria (Microccucos luteus, Staphylococcus epidermitis, Staphylococcus aureus and E. coli) and fungi (Candida albicans, Aspergillus niger and Cladospourium sp) by cup plate diffusion method. Minimal Inhibitory Concentration (MIC) values of each active extract were determined. The results obtained show strong activity of the ethyl acetate extract of various plant parts of the plant (except leaves) against bacteria and fungi used as test organisms.

Three extracts of Pulicaria dysenterica were examined for antibacterial activity using the agar disk-diffusion method against six bacterial strains. Some of these extracts were found to be active against some bacterial strains. The methanolic extract exhibited a superior level of antibacterial activity. All of the extracts were active against Vibrio chlorea.

Deproteinisation with acetonitrile (along with methanol or other reagents) is a useful and rapid technique in analysis of drugs or their metabolites in human serum. In this paper application of this simple technique in biopharmaceutical analysis using capillary electrophoresis (CE) is evaluated. Some drugs with different ionic and protein binding properties were selected and dissolved in human serum. The efficiency of deproteinisation of spiked serum samples with acetonitrile and further analysis with CE was evaluated for each sample with special interest on the neutral drugs. The results showed that deproteinisation method is more efficient for charged molecules with low protein bindings. For neutral, relatively non-polar compounds (such as praziquantel), a MEKC method is preferred. For neutral, highly polar molecules (such as methimazole), other means of sample preparation must be considered.

In order to improve local therapeutic techniques for the massively burnt patients and to minimize the pain associated with dressing change, the concept of topical film was utilized to formulate a topical antimicrobial spray. The commonly used topical antimicrobial silver sulfadiazine spray was formulated as a new drug delivery system. The release of therapeutic agents in vitro from medicated spray formulation was compared with that of the corresponding cream bases, utilizing a modified agar diffusion method. When using Pseudomonas aeroginosa as the test bacteria, silver sulfadiazine was found to produce a significantly larger zones of inhibition when used as the spray formulation instead of the cream form. Silver sulfadiazine spray, left in place for up to one day, appears to be as effective as the twice-daily cleansing and application of silver sulfadiazine cream. Also the periodic stability study of silver sulfadiazine in spray form, which was carried out using TLC, HPLC and particle size analyser methods, showed no significant degradation and crystal growth of active ingredient in the spray formulation after one year.

Impurities of drug substances may produce some side effects in patient. Diclofenac Na is a member of non-steroidal anti inflammatory drugs (NSAIDs) family, which is routinely used by patients for the treatment of rheumatoid arthritis and various pains. To develop a method for the determination of synthetic precursors which could be remained as impurities in raw drug materials, Na diclofenac powder was chosen in this study. High performance liquid chromatography was used to detect and separate diclofenac from its usual precursors. The chromatographic conditions were as follows: column; C18, mobile phase; methanol/water (55/45), flow rate; 1 ml/min, wavelength of detector; 254nm. The chromatogram obtained showed a reasonable separations of Na diclofenac and its precursors. This method of analysis is applicable in the final product inspection of Na diclofenac raw material.

Many different radiolabeled antibodies have been used for radioimmunotherapy and radioimmunoscintigraphy of human diseases in animal experiments. In order to study the in vivo tissue distribution of antibody, we labeled human nonspecific polyclonal IgG with Na125I using chloramine-T method. An animal model was developed by injecting turpentine in the posterior left thigh of Balb/c mice. Tissue distribution of 125I-IgG was assessed in normal and induced inflammation mice. Although labeled IgG accumulated in normal tissues such as liver, spleen and blood, its localization in inflammatory left thigh was significantly different from normal right thigh. Thus, by using the radiolabeling methods of IgG in order to increase the target-to-background ratio, antibody scintigraphy could be suggested as a powerful diagnostic tool for inflammation.

Pycnocycla spinosa aerial parts were collected weekly during four-month growth. Hydrodistillation and gas chromatography coupled with mass spectroscopy techniques were used for essential oil and sesquiterpenes investigation. Thirty-four components were identified, of which the characteristic sesquiterpenes were a -copaene, caryophyllene, a -humulene, b-ionene, d-cadinene, a -calacorene, caryophyllen oxide, a -cadinol, and b-eudesmol. The content of b-eudesmol in the essential oil varied 1.9-9.17%, and of a -cadinol did 0-5.59%. Plant harvested in Jun provided essential oil with high caryophyllen oxide. These results may indicate that essential oil of differ qualities can be obtained according to the harvest time of the plant.