DARU Journal of Pharmaceutical Sciences
Year:2003 | Volume:11 | Issue:2|Papers Count:8

The partition coefficients (Kpart, in octanol/water system) of a range of bidentate legends containing the 3-hydroxypyridin-4-one moiety were determined using shake flask and automated continuous flow methods (filter probe method)). The shake flask method was used for extremely hydrophilic or hydrophobic compounds with a Kpart, values greater than 100 and less than 0.01. For other legends which possess moderate lipophilicity (Kpart, values between 0.01-100) the filter probe method was used. Also the partition coefficient of four legends with moderate lipophilicity was determined by shake flask method in order to check comparability of these two methods. While the shake flask method was able to determine either extremely hydrophilic or hydrophobic compounds efficiently, the filter probe method was unable to measure such Kpart, values. Although, determination of the Kpart, values of all compounds is possible with the classical shake-flask method, the procedure is time consuming. In contrast, the filter probe method offers many advantages over the traditional shake flask method in terms of speed, efficiency of separation and degree of automation. The shake-flask method is the method of choice for determination of partition coefficients of extremely hydrophilic and hydrophobic legends.

Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD) virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(nbutyl) phosphate (0.3% w/w ) as solvent and tween 80 (1% w/w) as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR) virus (a lipid-enveloped virus) and Foot-and-Mouth Disease virus (a non-enveloped virus) were evaluated by virus spiking studies using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

Urinary excretion of ranitidine is known to be almost 70% of the intact drug , therefore this drug would be a good candidate for bioavailability studies using urine samples. In this study the bioequivalency of two marketed formulations using both urine and plasma samples were investigated. Ranitidine 150 mg tablets (generic) and Zantac 150 mg tablets were compared in a double blind crossover study using eight healthy male volunteers. A simple and rapid HPLC method was also developed to analyze the drug concentration in both urine and plasma. Double peak phenomenon, observed in plasma samples, was omitted when the urine samples were used. Bioavailability of the two formulations calculated from urinary data were not significantly different, whereas the plasma data were considerably different (based on Cmax, & Tmax but not AUC). Pharmacokinetic parameters resulted from urine regarding the rate of the absorption (Tmax-ud, (dDu/dt) max,Ka-ud) did not correlate well with their respective plasma parameters (Tmax, Cmax, Ka), whereas those of absorption extent and elimination rates (plasma AUC, K and urinary Du∞, K) were well correlated. It is concluded that the urine sampling which has advantages of easy sample collection and extraction could be used for determination of the extent of absorption and rate of the elimination of ranitidine, since similar parameters can be obtained with easier sample collection and extraction, whereas for determination of absorption rate, Cmax,& Tmax, plasma data are preferred.

U-937, a monocytic cell line was induced with Phorbol Myristate Acetate (PMA) for human tumor necrosis factor alpha (hTNF-α) production. An optimized RT-PCR was employed for construction of hTNF- α complementary DNA (cDNA). The resulted fragment was verified by restriction digestion mapping with PvuII. The verified fragment was cloned in pUC18 plasmid and transformants were pelletted onto LB agar medium containing ampicillin, X-gal and IPTG. The resulting white colonies were verified by PCR and cultured in LB medium containing ampicillin and IPTG. The biological activity and the quantity of hTNF- α expression was assessed by an ELISA method using a monoclonal anti hTNF- α antibody together with a bioassay utilizing L-929 line as sensitive cells.  

Tannic acid (TA) is naturally occurring polyphenols present in fruits and vegetables. In this study, inhibition of the carcinogenic potential of croton oil in normal and iron overloaded mice skin by TA is reported. Albino Swiss mice were given iron-dextran for two weeks and were pretreated with a single topical application of tannic acid. After one hour tumors were initiated by a single dose of 7,12dimethylbenz (a) anthracene (DMBA) the promoting agent croton oil was applied twice a week for 30 weeks. The appearance, number and percent tumor incidences were recorded. When compared to control groups, the pretreated groups showed a significant high inhibition of tumors incidences. Biochemical studies in mice skin tissues were based on the measurement of lipid peroxidation (LPO). TA diminished cutaneous LPO level in mice skin as compared to the untreated groups. This study showed that TA inhibits the augmentation potentials of croton oil and iron dextran significantly. A depletion in LPO levels in TA pretreated groups indicates that excessive generated oxidants in the mice skin tissues may be quenched by TA because of chelation of redox active iron and its faster elimination from the body. It is supposed that inhibition of iron mediated oxidative stress by TA may be responsible for diminishment of cutaneous tumorigenesis.

Sucralfate enema has been proposed and investigated in treatment of ulcerative proctitis, but its efficacy is still a matter of debate. Hydrocortisone enema is still an established drug in treatment of ulcerative proctitis. This study was designed to compare the effect of sucralfate enema with hydrocortisone enema. Patients with active sigmoidoscopic and histologic features of ulcerative proctitis were included. All patients had clinical manifestations of proctitis for at least four weeks prior to the study and had negative parasitic stool culture. The total of 25 patients entered the study. They were randomly divided in two groups; group I (n =11) and group II (n = 11) who received sucralfate and hydrocortisone enemas respectively for 4 weeks. Both groups had a significant improvement in clinical features, histologic activity and sigmoidoscopic evaluation in comparison with the baseline. Furthermore there was no significant difference between the two groups concerning mean changes of clinical, sigmoidoscopic, and histologic grading, after treatment. Considering the low cost and minimal adverse effects of sucralfate, and almost equal efficacy in comparison with hydrocortisone enema, its usage can be recommended.

Due to the good anticonvulsant activity of various 1,2,4-triazoles, several new N4-substituted triazolylthiazoles were prepared by the general method for 1,2,4-triazole ring closure. Anticonvulsant activity of compounds was measured against pentylenetetrazole-induced seizures in mice by intraperitoneal injections of different doses of the test compounds. Pretreatment of animals with Flumazenil (10 mg/kg, i.p.) as a benzodiazepine receptors antagonist did not have any significant effect on anticonvulsant activity of the test compounds. These results demonstrate that the anticonvulsant activity of N4-substituted triazolylthiazole agents is not probably mediated by direct interaction with benzodiazepine receptor complex.

The hydrodistilled oil from crushed dry fruits of Prangos asperula Boiss. subsp. haussknechtii (Boiss.) Hermst. et Heyn which is grown wildly in Iran was analyzed by GC/MS for the first time. Fifty-two constituents were identified of which δ-3-carene (16.1%), (β-phellandrene (14.7%), α-pinene (10.5%), α -humulene (7.8%), germacrene-D (5.4%), δ -cadinene (4.2%) and terpinolene (4.0%) were found to be the major components of the oil.