Iranian Journal of Pharmaceutical Sciences

In order to ensure the safety of parenterals, international pharmacopoeias and national standards have set up stringent guidelines and standards. Particulate contamination is a potential health risk caused by intravenous injection of particles large enough to potentially clog the small arteries. Particles could be produced through manufacturing and packaging or even dispensing of the pharmaceuticals.
The nature of the particles are varied and could be of drug itself, packaging debris, rubber, plastic, cotton, fiber and glass particles, which might be produced during the breakage of an ampoule. In this study, some of the small volume parenterals available in Iranian drug market have been investigated for the presence of particles.
Although, most of the tested samples passed national standard tests for particulate contamination of small volume parenterals, 40% of the samples were
rejected using the same protocols. Therefore, it appears that particulate contamination of parenterals creates an additional source of risk for patients who receive these medications, intravenously.

A sensitive procedure for determining total vitamin C (ascorbic acid + dehydrate ascorbic Acid) in a blood drop from a finger prick, before and after the administration of a vitamin C tablet is described. Analysis was carried out by high performance liquid chromatography with electrochemical detection (HPLC/EC).
Measurements were taken one hour, two hours and six hours after the administration of a 500 mg vitamin C tablet. D-Isoascorbic acid was used as the internal
standard and analysis was carried out using two C-18 columns connected in series and a phosphate buffer mobile phase. Dehydroascorbic acid in the samples was converted to ascorbic acid by incubation with DL-homocysteine for 30 minutes. The level of vitamin C in blood reached a maximum concentration after two
hours.

Addition of n-butyl nitrite to isolated rat hepatocytes caused an immediate glutathione depletion followed by an inhibition of mitochondrial respiration, inhibition
of glycolysis and ATP depletion. At cytotoxic butyl nitrite concentrations, lipid peroxidation occurred before the plasma membrane was disrupted.
Cytochrome P-450 inhibitors inhibited peroxynitrite formation and prevented butyl nitrite-induced mitochondrial respiration inhibition, ATP depletion, lipid
peroxidation and plasma membrane disruption. However, glutathione depletion, S-nitroso-glutathione (GSNO) formation, or the inhibition of glycolysis was not
affected by cytochrome P-450 inhibitors. Glutathione-depleted hepatocytes were resistant to butyl nitrite which suggests that cytotoxicity and peroxynitrite formation results from GSNO formation. Peroxynitrite formation was also inhibited by reactive oxygen scavengers. These findings suggest that cytochrome P-450 isoforms (particularly CYP2E1) act as a source of superoxide anion radicals in the formation of cytotoxic peroxynitrite from nitric oxide.

In order to investigate the effects of dimethylamino substituent at postion 2 of the dihydropyridine nucleus on its activity, dialkyl 1,4-dihydro-2-[2-dimethylamino)
ethyl]-6-methyl-4-(1-benzyl-2-alkylthio-5-imidazolyl)-3,5-pyrdinedicarboxylates (6a-f) were synthesized. The synthesis was started from dialkyl 1,4-dihydro-2,6-dimethyl-4-(1-benzyl-2-alkylthio-5-imidazolyl)-3,5-pyridinedicarboxylates (5a-f) which their synthesis and effects as calcium channel antagonist on guinea-pig ileum has been reported previously. Rabbit jejunum was used to determine the relaxant or antagonistic activity of the synthesized compounds.
Some of the compounds (6c-e) inhibited the spontaneous contractile activity of jejunum, dose-dependently and completely, while high-K+ contracted tissues were
relaxed partially.

The essential oils of the aerial parts of three different Artemisia species (A. scoparia, A. diffusa, A. turanica) growing wildly in the northeast of Iran were analyzed by GC-MS. Twenty-two, twenty-six, and thirteen components were identified in the essential oils of these plants, respectively. The major constituents of the oil of A. scoparia were b-pinene (16.10%), carvacrol (13.81%), limonene (8.82%), cis-ocimene (8.38%), methyl eugenol (7.62%), and transocimene (7.17%). Camphor (25.5%), 1,8-cineol (25.0%), b-thujone (22.%), and a-thujone (6.0%) were the major components identified in the volatile oil of A. diffusa. The main identified compounds in the volatile oil of A. turanica were 1,8-cineol (40.94%), cis-verbenyl acetate (19.03%) and camphor (11.03%). The identified components and their percentages in the essential oil of three different Artimisia species in this study were quite different. Since the chemical composition of the oil depends on various environmental conditions, therefore, these differences can be expected.

The essential oils obtained from fresh fruits and terminal branchlets with adherent leaves of Cupressus sempervirens L. cv. Cereiformis Rehd. growing in Iran, were analyzed by GC-MS, and screened for bacteriostatic and fungistatic activities. Thirteen components were identified in the essential oils. The main
constituents of both fruits and leaves were ?-pinene, Æ-3-carene, ?-terpenyl acetate and terpinolene. The essential oil of leaves and fruits showed no antimicrobial activity against, Bacillus subtilis, Candida albicans, Escherichia coli and Staphylococcus aureus. The defatted ethanolic extract of leaves and fruits were examined for the presence of alkaloids, flavonoides, and saponins. The nonvolatile compounds in leaves and fruits were quite rich in tannins and flavonoids but the amounts of alkaloids and saponins were not significant.

Inabilities to attain adequate aqueous solubility and stability have made the preparation of a clinically suitable formulation of taxol difficult. Addition of nicotinamide (ND), 2-hydroxypropyl-b-cyclodextrin (HPßCD), polyethylene glycol, (PEG), bile salts (BS, 50:50 sodium cholate: deoxycholate), and cremophor
EL can improve the solubility of taxol. Studies were undertaken to compare the stability of taxol in HPßCD (20%), ND (20%), PEG (20%), BS (20%), and cremophor
EL (cremophor: ethanol 0.5% of each) solutions at 25, 37, 50, and 60 oC. Taxol concentration was measured by HPLC method. The rate of degradation
proceeded in a Log-linear fashion and increased progressively with the elevation of temperature in all solutions except in HPbCD which taxol had negligible degradation. In the absence of added agents, taxol exhibited the lowest and highest stability at pH 1.2 and 4.5, respectively. Taxol was most stable in HPbCD followed by PEG and then ND. The stability of taxol increased linearly with the HPbCD concentration (0-5% w/v). Due to the observed improved stability and solubility, HPbCD may be considered for pharmaceutical studies as a suitable stabilizer for formulation of taxol.

A multiple linear regression model is proposed to calculate capacity factor of analytes using structural features computed using HyperChem software. The
chemical descriptors of analytes were computed using HyperChem software and regressed against the experimental capacity factors of analytes collected from the literature. The absolute average percentage deviation (AARD) and individual percentage deviation (IPD) were calculated as accuracy criteria. The accuracy of the proposed method was compared with that of a previously reported linear solvation energy relationship (LSER). The proposed method was tested on ten experimental data sets and mean ± standard deviation of AARDs were 48.5 ± 20.4 and 130.1 ± 79.7, respectively, for the proposed and LSER models in which the mean difference was statistically significant (p<0.01). The distribution of IPDs sorted in three subgroups, i.e. £ 45%, 45%-90%, and >90 %, shows the superiority of the proposed model over the LSER. A significant improvement in capacity factor modeling was achieved and the improvement factor is about 2.7. The descriptors
could be easily computed and the calculations are straightforward. Therefore, the model is suggested to be employed in practice, however, the efforts should be continued until providing more accurate models.