Iranian Journal of Pharmaceutical Research
Volume:4 Issue: 3, Summer 2005

Quinolones are a very important family of antibacterial agents that are widely prescribed for the treatment of infections in humans. Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest. Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones. The 4-pyridone-3-carboxylic acid associated with a 5, 6-fused aromatic ring is the common chemical feature of bactericidal quinolones. In the resulting bicyclic ring, the 1-, 5-, 6-, 7-, and 8-positions are the major targets of chemical variation. Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a cyclic amine residue at position 7 and adding new residues at position 1 of the quinolone ring, have led to improved breadth and potency of antibacterial activity and pharmacokinetics. One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxacin and garenoxacin. However, some of these structural changes have been found to correlate with specific adverse effects: the addition of fluorine or chlorine at position 8 being associated with photoreactivity, e.g. sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g. sparfloxacin and grepafloxacin. The clinical utility of this expanding class of antimicrobial agents, and the lower propensity for the development of resistance with the newer quinolones will need to be continually monitored in the changing therapeutic environment. Antibiotic drug choice will remain difficult in the presence of increasing resistance, but introduction of the new quinolones has created a new and exciting era in antimicrobial chemotherapy.

In this study, the effects of various hydrophilic (HPMC and Carbopol 971) and plastic (Ethylcellulose and Eudragit RL100) polymers on the release profile of diltiazem HCl from matrix tablets were evaluated in-vitro. For this purpose, tablets containing 60 mg of diltiazem HCl along with various amounts of the aforementioned polymers were prepared using the wet granulation technique. Tablets prepared were placed in a USP apparatus I dissolution tester containing a pH-1.5 HCl solution for the first 2 h and a pH-6.8 phosphate buffer for the next 10 h of the study. The amount of drug released was determined at 237 nm by a UV-visible spectrophotometer. The results showed that all the polymers used in this study could slow down the release of diltiazem HCl from the matrices prepared. This effect, except for HPMC, generally increased proportionately with the amount of polymer. HPMC imparted the best control over drug release and could sustain it for approximately 6 h. All the matrices prepared had a burst release initially; however, it was minimum with HPMC-containing formulations. Fitting of release data to different kinetic models showed that HPMC-matrices conformed best to Hixson-Crowell model, ethylcellulose-matrices to Higuchi and both Eudragit RL100 and Carbopol 971-formulations to either of Hixson-Crowell, Higuchi and first-order kinetics. Release exponent (n) derived from Korsmeyer-Peppas equation for the studied formulations implied that the release of diltiazem HCl from HPMC-matrices was non-Fickian (0.62-0.66) and that of ethylcellulose-formulations was Fickian (n~0.4). The values of n for Eudragit RL100 and Carbopol 971-matrices ranged from 0.46-0.59, indicating that the drug release was mainly governed by diffusion. Briefly, HPMC was found to be suitable for sustaining the release of diltiazem HCl from matrix-type tablets. Nevertheless, to achieve better results with this polymer, further investigations seem to be necessary.

In this study, different derivative spectrophotometric methods are proposed for the simultaneous determination of chlorpheniramine maleate (CP), phenylephrine HCl (PE) and phenylpropanolamine HCl (PP) in their ternary mixtures and in pharmaceutical dosage forms. Spectra of single component and ternary mixtures of various concentrations and combinations from zero- to fourth-derivation were obtained. Also the spectra of the excipients including lactose, starch, and microcrystalline cellulose were obtained to study the possible interference from matrices. Zero-crossing derivative spectrophotometry based on recording the second-derivative curve for PE at 286.5 nm and fourth-derivative curve for PP at 220 nm were used for determining each component. Third component, CP, was determined by measuring absolute amplitudes at 265.8, 262.2, 269.5, and 273.8 nm in its second derivative spectra. Results showed that the matrices have no interferences. The calibration curves were linear in the range of 1-8 µg/ml for PE; 5-30 µg/ml for PP; and 2-8 µg/ml for CP. The limits of detection were 0.2 µg/ml for PE, 0.1 µg/ml for PP, and 0.3 µg/ml for CP. The mean percentage recoveries obtained for different synthetic mixtures by using this method were 95.3% with coefficient of variation of 4.3% for PE, 101.5% with coefficient of variation of 1.4% for PP, and 99.4% with coefficient of variation of 1.5% for CP. This method has been applied successfully for the determination of PE and PP in its combination with CP in Antihistamine Decongestant tablets with a high percentage of recovery, good accuracy and precision.

Measles has been a major cause of illness and death in children and vaccination against the disease is part of the WHO global immunization program. A suitable vaccine should create maximum immune response against the pathogen and must be safe for the user. Thus, after production, vaccines must be analyzed and controlled by the producer and confirm by relevant governmental organizations. The Food and Drug Control Lab (FDCL), Ministry of Health, is the secondary control center on potency of vaccines in Iran. In this study, we have set up the WHO and NIBSC methods in FDCL and compare these methods on determining the potency of measles vaccine. Measles vaccines were obtained from Razi Institute Iran. Nine dilutions of vaccine (10-1 to 10-5) in 0. 5 log interval were mixed with Vero cell suspension and seeded. In WHO method, the cells were incubated at 36ºC for 10 days, during which the cells were checked for cytopatic changes everyday. To set up the assay, we tested the vaccine dilution with four different cell suspensions (2ױ05-5ױ04/well) and four different concentration of serum (2. 5-10%). Based on our results, in the assays, 5% serum and 1ױ05 cells were used. The potency assay was performed with six different vaccines produced in one batch and the mean potency for Measles was 104. 32 ± 0. 24 CCID50/vial for a ten-dose vial. In NIBSC method following seeding of Vero cells, the medium was removed after 3 hours and overlay was added. Then the plates were incubated at 35ºC for 10 days. After incubation period, the overlay was removed, the plaques were stained with methyl violet and counted. This assay was repeated three times and the mean of the results was 5. 83 ± 0. 03 log10 PFU/dose. In this study, we have set up the WHO and NIBSC methods and results indicated that the potency of the vaccine is in acceptable range in either method. Furthermore, the WHO method is simple and less time consuming compared to NIBSC which is complicated and requires more effort to produce reproducible results.

Power stations produce a range of magnetic fields more than 20 mT which are harmful to those working or living around them. Several investigators have reported an increased health risk due to exposure to electric and magnetic fields (EMF) at 50 and 60 Hz. Several studies have been reported especially with increased tumor incidence, effects on reproduction and development, and neural and behavioral changes.This study evaluated the possible effect of static MFs 50 Hz on the secretion of Testosterone, LH and FSH hormones in male rats. Forty eight Wistar male rats (same range of age and weight) were randomly divided into four groups. Animals in group 1 were used as a sham exposure group. After one-week adaptation they were placed in exposure to three MFs for 40 minutes daily for 17 days. Group 2, 3 and 4 were exposed with 6, 12 and 24 mT static MFs at 50 Hz respectively. After experiments animals were killed and their bloods were collected in separated tubes and their serums were separated using a centrifuge with 3500 RPM for 15 min.Hormones were measured using gamma counter equipment with RIA and IPMA methods. The results were analyzed by ANOVA statistical method. Our results show that testosterone, LH and FSH have not changed significantly (p< 0.05) using these static MFs intensities. therefore it can be concluded that at least the static MFs used in this study (with these intensities and duration) can not affect the secretion of hypothalamic-pituitary-gonadal hormones.

It has been shown that stress and chronic pain could prevent the development of tolerance to morphine analgesia, which appears to be related to the activation of hypothalamus–pitutitary–adrenal (HPA) axis, activation of neuroendocrine systems and changes in neurochemical levels. Moreover, the involvement of nitric oxide (NO) in the development of tolerance to morphine analgesia has been implicated. In the present study, we have tried to investigate the effect of swim stress, as a painless kind of stress, on the development of tolerance to find out whether the inhibition of tolerance is mediated by the direct effect of pain on the pain conduction pathway, or by its stress aspect. Besides, we evaluated the probable interactions between swim stress, nitric oxide level and the development of morphine tolerance. Adult male Wistar rats, weighing 180-220 g, were used in all these experiments. The experimental groups received chronic morphine (20 mg/kg, i.p), swim stress in 20ºC water bath (4 min), or a combination of swim stress and chronic morphine (20 mg/kg, i.p), each for 4 days, while the first control group received saline (1 ml/kg, i.p) for 4 days. On the 5th day, all the experimental and control groups received a single dose of morphine (10 mg/kg i.p). The second control group received saline for 5 days. The intact group received only one single dose of morphine (10 mg/kg, i.p). All the mentioned groups were subjected to tail-flick and formalin tests on the 5th day. Other experimental groups were subjected to the assay for measuring nitrite as an indicator of NO, using the Griess method. Our results showed that co-administration of swim stress with chronic morphine prevented the development of morphine tolerance and the level of NO increased in the presence of swim stress (p<0001). The combination of morphine and swim stress significantly decreased NO production in comparison with the chronic morphine administered group (p<0.001). These data suggest that the activation of HPA axis and consequently the suppression of (NO) production induced by chronic morphine, lead to the inhibition of morphine tolerance

High performance liquid chromatography coupled with photodiode array detector (HPLC-DAD) has been reported to quantify isolated flavonoids or these compounds in complex biological matrices, such as Chinese herbal drugs and products from factories. This work was designed, therefore, to develop an HPLC-DAD system to separate quercetin, luteolin and apigenin and to quantify them in extractive solutions from Marchantia convoluta. Flavonoids were analyzed on a Kromasil RP-C18 column; using a mobile phase, consisted of methanol- acetonitrile-acetic acid-phosphoric acid-H2O (200:100:10:10:200, V/V); under the following conditions: detecting wavelength, 352 nm; flow rate, 0.60 ml/min; the sensitivity, 0.05 AUFS and the volume of injecting sample, 6.0 μl. The HPLC system was operated at ambient temperature (28±1°C). The method showed linearity for quercetin, luteolin and apigenin in the range 2.0-20.8, 2.2-24.0 and 1.6-20.0 μg/ml respectively, and the R.S.D. of the slope of the three lines was, respectively, 0.33%, 1.21% and 2.49% for quercetin, luteolin and apigenin. The aqueous and ethanol 80% extractive solutions showed linear response 1.5-15 μl/ml and ethanol 50% extractive solution in range 1.0-10 μl/ml. Precision and accuracy were determined for ethanol 80% extractive solution, in concentration of 10 μl/ml. The recoveries were 95.92-98.10%, 92.18-95.13% and 98.72-103.19% for quercetin, luteolin and apigenin respectively. RSD of results was 2.83-3.62%. The HPLC method showed an excellent performance in separating the flavonoids quercetin, luteolin and apigenin in Marchantia convoluta extracts, since the presence of interference has been previously evaluated and the mobile phase was chose carefully

There have been efforts to overcome the problem in treatment of cancer using medicinal plants. It has been shown that Citrus essential oil of contains different terpens with antitumor activities. In this study we sought to determine the cytotoxicity of essential oils of Iranian Citrus limon (L.), C. medica (L.), C. sinsensis (L.) peels on cancer cell lines. Essential oils were prepared by hydrodistilation and characterized by GC-MS. The effects of C. limon (5-40 µg/ml), C. medica and C. sinensis (0.25-10 µg/ml) on two human tumor cell lines (MCF-7 and Hela) were determined. Different concentrations of essential oils were added to cultured cells and incubated for 72 h. Cell survival was evaluated using the MTT-based cytotoxicity assay. While limonene comprise about 98.4% and 98.8% of content of C. limon and C. sinensis essential oils respectively, its’ percentage in C. medica was only 56.6%. In C. medica there was a considerable amount of β-pinene, γ-terpinene, α-terpinolene and trans-α-bergamotene. IC50 of essential oil for MCF-7 cell line was: C. limon ≈ 10 µg/ml, C. medica ≈ 1 µg/ml and C. sinensis ≈ 0.5 µg/ml. For Hela cell line IC50 was: C. limon ≈ 17 µg/ml, C. medica ≈ 1 µg/ml and C. sinensis ≈ 3 µg/ml. Our findings revealed that C. limon and C. sinensis had a greater cytotoxic effect on MCF-7 than that on Hela cells. Also, comparing IC50, our findings indicated that C. medica and C. sinensis were more cytotoxic than C. limon. Comparison of the essential oil component of C. limon with C. medica, shows the presence of β-pinene (16.3%), α-terpineol (11.3%), γ-terpinene (4.4%), and trans- α-bergamotene (3.4%), which were not found in C. limon. Hence, it could be concluded that these components may have greater cytotoxic effects or they may also have synergistic effects with limonene