Iranian Journal of Pharmaceutical Sciences

Piroxicam is a non-steroidal anti-inflammatory agent which has an extensive use in rheumatic disorders. Since its skin penetration is still a subject for research, the aim of this study was to evaluate the effect of dimethyl sulfoxide on percutaneous penetration of piroxicam gel formulation through skin. In this study, as a model, two types of 0.5% piroxicam new gels, so called red and green gel, were prepared using 5% (w/w) DMSO only for the red gel. Water, ethanol and propylene glycol were the solvent composition specified by a triple phase diagram, in addition to carbomer P934 and hydroxypropyl methylcellulose as the gel bases. The release and dermal penetration of the drug were measured and compared with a commercial brand using static diffusion cells and hairless rat skin as a biological membrane, by UV spectrophotometer. Also, piroxicam serum level was measured after application of 1 g gel on the deltoid muscle, twice daily for two weeks, in three groups of healthy male volunteers. The results of all physico-chemical controls for the gels indicated an acceptable criteria. The penetration of piroxicam through animal skin showed a good linearity between the square root of time and amount of piroxicam released from the gels. The in vitro study showed that application of DMSO had no significant effect on percutaneous penetration of the drug through animal skin. In human study, the red gel containing DMSO had the highest piroxicam serum level with a relatively meaningful difference between the results compare to the green and commercial gels (p<0.05). But the green and commercial gels had no statistical difference. This preference might be related to the in vivo DMSO positive effect as a penetration enhancer, contrary to the in vitro results. Therefore, relying on laboratorial data is not always sufficient.

Gel dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from a hostile environment. The aim of this work was to investigate the properties of carbopol 934P polymeric system in water-misible cosolvents such as glycerin and alcohol. Benzocaine is a local anesthetic and the mucosal gel formulation is applied in the treatment of dental pain. Samples were prepared by simply dispersing different amounts of Carbopols (0.5-3%) into the alcoholic solution at the room temperature and were kept at 4, 25 and 40 °C. All these systems were then characterized for distribution, bioadhesiveness on the mucosa, physical stability and drug release. The silastic membrane was employed. The membrane must not be a barrier for drug transport. Franz diffusion cell used to study in vitro drug release. The increase in carbopol concentration caused increased viscosity and bioadhesiveness. Neutralization of pH in various concentrations of carbopol gels showed resulted in increased viscosity. A relationship between the viscosity and bioadhesive strength was shown in the neutralized carbopol gels. On the other hand, the results indicated that increasing amount of alcohol and glycerin reduced drug release. In contrast, by increasing the amount of water, elasticity and release rate was increased. Vision-gel® was used as a reference for comparison with the oromucosal gel formulation. The results showed that diffusion of benzocaine from oromucosal gel and commercial sample followed Higuchi law.

Dacarbazine (DTIC) is a synthetic chemical antitumor agent which is used to treat malignant melanoma and Hodgkin’s disease. DTIC is a prodrug which is converted to an active form undergoing demethylation by liver enzymes. The active form prevents the progress of disease via alkylation of DNA strand. In the structure of this drug, the imidazole ring, a triazen chain and carboxamide group exist. Based on the literature, the ring and carboxamide group do not have a key role in antitumor activity of the drug. On the other hand, imidazole ring has a unique tautomerization which may participate in the mechanism of action of DTIC and carboxamide group may determine the rich guanine pieces in DNA strand. In order to investigate the mechanistic role of imidazole group and its known tautomerization in DTIC cytotoxicity, derivative of DTIC with a pyridine ring (3-(3,3-dimethyl-1-triazenyl)pyridine, (compound I) instead of imidazole ring was synthesized. In the following, the cellular and molecular mechanism of cytotoxicity induced by DTIC and its pyridine derivative toward the isolated rat hepatocytes were studied and compared. Hepatocyte reactive oxygen species (ROS) generation was significantly increased by both DTIC and compound B before cytotoxicity ensued. In addition, DTIC and compound I induced lysosomal damage and hepatocyte protease activation. Endocytosis inhibitors, lysosomotropic agents or lysosomal protease inhibitors
also prevented both DTIC and compound B induced hepatocytes cytotoxicity. Furthermore desferoxamine (a ferric chelator), antioxidants or ROS scavengers (catalase, mannitol or dimethylsulfoxide) prevented both DTIC and compound I cytotoxicity. It is concluded that H2O2 reacts with lysosomal Fe2+ to form hydroxyl radical which (Haber-Weiss reaction) causes lysosomal membrane disruption, proteases and other digestive enzymes release and finally the cell death.

The chloroform soluble fractions of ethanolic extracts of five Inula belonging to the Compositae family were evaluated for cytotoxic activity against five different cell lines including CACO2 (human colon adenocarcinoma), MCF7 (human breast adenocarcinoma), HEPG2 (human hepatocellular carcinoma), VERO (green African monkey kidney) and WEHI164 (balb c mouse fibrosarcoma). Cytotoxicity was assessed by MTT assay. Among these five species, Inula oculus christi, exhibited better cytotoxic effects.

According to Iran’s folk medicine, camphor, a crystalline ketone obtained from essential oils of Cinnamomum camphora, has both sexual behavior attenuating and enhancing properties. This study examined the effects of camphor on sexual behavior in male rats. Twenty four sexually mature male Sprague-Dawley rats were randomly divided into 4 groups receiving daily i.p. injections of olive oil as vehicle (2.5 ml/kg) or camphor at 2.5, 12.5 or 50 mg/kg for 7 days. Afterwards, mount latency (ML), mount frequency (MF), intromission latency (IL) and intromission frequency (IF) of male rats in the presence of sexually receptive females rats were recorded. There was no significant difference in MF or IF from control and experimental groups. However, at the 50 mg/kg dose, camphor reduced the ML and IL relative to that of control rats. The finding indicates that at this dose, camphor had sexual desire and sexual performance enhancing properties.

1,3-dialkyl 3-phenylpyrrolidine-2, 5-diones were modified to produce potential steroid sulphatase inhibitors. These modifications were aimed at producing compounds, which could be expected to bind reasonably well to the active site of the steroid sulphatase enzyme but could not be hydrolyzed readily by the enzyme due to the covalent S-C bond present. In this regard the sulphinic acid derivatives of di-substituted 3-phenylpyrrolidine-2, 5-diones were prepared. On biological testing, only compound 4-(2,5-dioxo-1, 3-dipentylpyrrolidine-3-yl) phenylsulphinic acid (F5) was found to be an inhibitor of the steroid sulphatase enzyme from human placenta and was about twice as potent as the known inhibitor danazol.

A novel chemical detergent/disinfectant formulated based on persulfate salts, germicide P® , is available for disinfection of surfaces and medical devices at the room temperature. Because of the resistance of hospital-resident microorganisms, the antimicrobial activity of this compound is evaluated in the present study. The tests conducted with this disinfectant included bactericidal tests against 25 clinical isolates of gram negative bacteria of Escherichia coli, Pseudomonas aeruginosa as well as 25 clinical isolates of gram positive bacteria of Staphylococcus aureus with and without 5% bovine serum albumin (BSA) as dirty condition. All of the experiments also performed using standard strains and serial dilution method applied to find minimum bactericidal concentration (MBC) of germicide P® against the selected bacteria at different exposure times. Also, to determine the ability of germicide P® for disinfection of surfaces, standard surface tests were conducted using all of the clinical isolates as well as standard strains. According to the in vitro results of the tests, germicide P® found to be a promising product with the MBC of 1/10 after 5 min. against all of the tested bacteria at the room temperature, however, the results of the surface tests indicated that a significant reduction in the efficacy of germicide P® was observed and the MBC dropped to 1/5. In conclusion, surface antisepsis without intervention of organic materials in the concentration range of 1/5 was achieved with this new disinfectant.

The essential oils of leaves and flowers of Peucedanum ruthenicum (M. Bieb.) Rochel (Umbelliferae) were prepared by hydrodistillation separately and analyzed by GC and GC-MS, and the composition of both essential oils were compared together. Sixteen and eleven compounds were identified in leaves and flowers essential oils representing 100% and 96.4% of total oils, respectively. The major components were thymol (57.79%), b-bisabulene (6.10%) for the leaves oil, germacrene-D (45%) and germacrene-B (18.5%) for the flowers oil. The amounts of monoterpenes and sesquiterpenes were not found nearly to be equal in oils of the two parts of the plant.