Iranian Journal of Pharmaceutical Sciences

This work summarizes how the efficiency of pharmacopeias (USP and BP) procedures for the iodometric determination of pencillins can be significantly enhanced through the use of beta-cyclodextrin (β-CD). In the commonly used iodometric method, titration takes about 30 min; 15 min to hydrolyze the antibiotics and 15 min for reaction between iodine and hydrolyzed species. The experimental results indicate that β-CD accelerates both hydrolysis of amoxicillin, ampicilline and cloxacilline and the reaction of their hydrolyzed products with iodine. Effect of different parameters such as sodium hydroxide, hydrochloric acid concentrations, and the waiting times in the presence of β-CD on the total titration times reported in pharmacopeia are evaluated. Finally, it is shown that the analysis times of iodometric assay for ampiciline an d amoxicilin in the presence of 0.108 mg.ml-1 β-CD are reduced from 30 to 5 min and those of cloxaciline is reduce to 10 min. The iodometric titration in the presence of β-CD is referred to as modified USP. Student t-tests at 95% level shows that there are no significant differences between USP and Modified USP. It is also shown that β-CD increases the stability of penicillin-G relative to USP buffer No.1. The reliability of the proposed method is evaluated by analysis of the above mentioned antibiotics in different pharmaceutical forms. The results show that the modified method can be successfully applied for the assay of cloxaciline injection vial, amoxicillin and ampicillin capsules and suspensions.

The plant gums obtained from Prunus armeniaca and Prunus domestica (Familym Rosaceae) were studied for their sustained release potential in comparison with hydroxypropyl methyl cellulose (HPMC), a semi-synthetic matrix polymer, using diclofenac sodium. Matrix tablets of diclofenac sodium were prepared using different ratios of gum alone and in combination (i.e. 1:1) with diclofenac sodium and other excipients. The formulated matrix tablets were evaluated for their thickness, hardness, weight variation, friability, drug content and in vitro release studies. These studies demonstrated that P. armeniaca and P. domestica gums used alone could not control drug release efficiently, however, extended drug release (up to 10 hours) was obtained when both gums were used in combination (1:1). The dissolution data was fitted into zero order, first order, Higuchi and Korsmeyer equation, which dictated that the release mechanism is diffusion as well as erosion controlled-drug release. FTIR studies showed that there was no interaction between drug and plant gums used. Among various formulated batches, F-5 did not significantly differ from F-7 and commercially available formulation (Voltral SR®, Novartis Pharma, Pakistan) with respect to drug release.

In the recent decades, a lot of efforts have been directed for the discovery and production of anticancer agents. Plant kingdom is one of the main sources which has attracted the attention of investigators for finding new medicines including anticancer agents. In the present study, the cytotoxic effects of the extracts of five plants, native of Iran including Salvia mirzayanii, S. macrosiphon, S. multicaulis,
Juniperus excels, and Peganum harmala, against HepG2 cell lines were investigated. Cytotoxicity was assessed by MTT test, and comparison of the IC50s revealed that the extracts of aerial parts of the J. excelsa had the strongest cytotoxic effects followed by S. mirzayanii, and the extract of the root of P. harmala with IC50s of 0.54, 1.52, and 2.50 mg/ml, respectively. The extracts of S. macrosiphon and S. multicaulis had no significant cytotoxic effects against HepG2 cells. The cytotoxic effects of J. excelsa is seemed to be due to ATP depletion as ATP levels of HepG2 cells incubated for 24 h with 0.5, and 0.7 mg/ml of the extracts of J. excelsa was decreased to 47% and 27% of control, respectively. The ATP depletion was timedependent and ATP was depleted before cytotoxicity ensued. Oxidative stress was not important in cytotoxicity of J. excelsa as lipid peroxidation and GSH depletion was not significantly different from control cells. However, cytotoxicity of S. mirzayanii was not accompanied by ATP depletion or oxidative stress. The exact
mechanism(s) of cytotoxicity of these extracts needs further investigation.

Lisinopril dihydrate (angiotensin converting enzyme inhibitor) is a lysine derivative of enalaprilat and does not require hydrolysis to exert pharmacological activity. It has an extensive hepatic first pass metabolism resulting in a bioavailability of 6-60%. To overcome the poor bioavailability of the drug, transdermal patches have been prepared. The present study also aims at optimization of the formulation
by incorporating the penetration enhancers in different concentration and ratios. The patches were prepared employing hydroxy propyl methyl cellulose (HPMC) and polyvinyl alcohol (PVA) in a 1:1 ratio as polymeric matrix using glycerol as plasticizer in 6% concentration. Binary solvent system (water-methanol) in a ratio of 70:30 was taken for the study. The transdermal devices were fabricated on glass
substrate using solvent casting technique. Dimethylsulfoxide (DMSO) and propylene glycol (PG) were added as the penetration enhancers individually and in blends in different concentrations and ratios. Various physico-chemical evaluation parameters were carried over prepared patches to ascertain their integrity and physical stability at normal and accelerated temperature conditions. Optimization of the penetration
enhancer’s concentration and ratio was done by performing in vitro diffusion rate studies using Keshary-Chein diffusion cell on Goatskin. The patch containing DMSO:PG in the ratio of 70:30, at 10% showed the best in vitro drug flux and possesses excellent physico-chemical properties at normal and accelerated temperature conditions. It could be concluded that all patches prepared increased the drug flux
through skin but optimization of the formulation yields highest drug flux through patch containing DMSO and PG in 10 % concentration.

Compounds especially from natural sources are capable of protecting against reactive oxygen species (ROS) mediated damage. Therefore, there is a growing interest in novel substances exhibiting antioxidant properties. Several marine environments can provide a rich source of novel biologically active compounds. The aim of this paper is to evaluate in vitro antioxidant properties of six sponge species
collected from Kish Island in the Persian Gulf. We evaluated the effects of different concentrations of the dichloromethane and methanolic extracts of six sponges on scavenging DPPH and OH free radicals. The activities of these extracts were compared with those of commercial antioxidants such as gallic acid. The maximum level of DPPH radical scavenging (0.234± 0.033 mg/ml) was observed for the methanolic extract of Pseudosaberites clavatus in the reaction mixture. Also, most of sponge extracts exhibited medium to high hydroxyl radical scavenging activity. The results of this study suggest that marine sponges of the Persian Gulf are promising sources of antioxidants.

In many herbal markets medicinal plants are sold in dried forms which make it difficult to authenticate them and recognize the adulterations. In the present study the preliminary pharmacognostic parameters including microscopieal studies, extractive values and thin layer chromatography analysis of roots of Doronicum scorpioides (Asteraceae) were evaluated. Three fractions of the plant (hexane,
dichloromethane and ethanolic) were applied to the silica gel plates and run in nonpolar, semi polar and polar mobile phases. Chromatographic spots were visualized using different spray reagents. The preliminary screening of the D. scorpioides roots revealed the constituents of the different fractions of the roots including alkaloids, flavonoids, triterpenes saponins, coumarins and essential oils which can be a useful guide for further phytochemical and pharmacognostic research. This is the first report on phytochemical constituents of D. scorpioides roots. Also the pharmacognostic investigation of the D. scorpioides root can be a reliable method for authentication of the medicinal part of the plant and to recognize any adulterations.

We have previously synthesized new N-alkylated azoles (1b-7b) as antifungal agents. Here, we evaluated the antibacterial activities of these compounds against two gram positive and two gram negative bacteria by broth microdilution method. The aminothiazole derivative (7b) showed an excellent antibacterial activity. Other compounds exhibited moderate to good antibacterial activity. All compounds are more
active against gram positive than against gram negative bacteria.

The efficiency of four β-lactam antibiotics meropenem, imipenem, ceftazidime and ceftriaxone were tested on three strains of Agrobacterium, tumefacience LBA4404, AGL0 and C58 and were compared with the commonly used antibiotic, cefotaxime. Meropenem exhibited the most effective antibacterial activity against Agrobacterium tumefacience LBA4404, AGL0 and C58. In addition to the high levels of activity of the antibiotics meropenem and imipenem on Agrobacterium inhibition (MIC less than 10 mg.l-l and MBC less than 150 mg.l-l), they allowed a high rate of shoot formation and had no significant negative effects on shoot and root weights of wheat explants. Therefore, they can be recommended for Agrobacteriummediated transformation projects for wheat.

Due to various usages of Satureja species or their oils, we were interested in studying essential oil contents and compositions of Satureja species in Iran. So, the essential oil of aerial parts of Satureja bachtiarica Bunge. growing in Iran was obtained by hydrodistillation and was analyzed by GC-MS. Twenty eight compounds constituting 99.80% of the oil were identified and yield of the oil was 2.7% (V/W). The major components were found to be thymol (65.1%), γ-terpinene (15.0%), β-caryophyllene (4.85%), p-cymene (4.4%), linalool (3.5%) and borneol (3.05%).

Geographic proximity has been shown to be a significant factor in healthcare utilization and also one of the important dimensions in the concept of accessibility. In this study, we aimed to evaluate the geographic accessibility to pharmacies in city of Shiraz. A geographic information system approach was obtained to evaluate geographic accessibility to pharmacies. A stratified random sampling was conducted
to choose adequate points as the representative of whole city to measure their distance in both pedestrian and driving condition to the pharmacies. To measure the pedestrian accessibility of selected blocks in Shiraz, different distances of 150, 300, 450, 600 and 750 meter, and to measure driving accessibility different network distances of 5, 10 and 15 min were considered as acceptable levels of geographic
accessibility. In terms of pedestrian accessibility, the analysis showed that about 45% and 15% of sample blocks have accessibility to at least one pharmacy in their 750 meters in normal days and holidays, respectively, based on straight line distance. In terms of driving accessibility, our analysis indicated that in normal days and also in holidays about 98% of sample blocks in Shiraz have at least one pharmacy in their 15 min based on network analysis and considering traffic limitation. In spite of implemented policy by food and drug organization to distribute pharmacies equitably through the whole city, geographic accessibility to pharmacy doesn’t seem to be desirable in Shiraz and some other policies may be needed to make the situation better.