Pharmaceutical Sciences
Volume:12 Issue: 3, 2007

Nardostachys Jatamansi DC has been used in traditional medicines of various countries because of seadative, anticonvulsion and analgesic properties. In this study, first, the rhizome of N. Jatamansi was extracted by hydromethanolic (70%) solvent and then, the presence of valporoates, in total extract, was revealed by GC-MS analysis of its n- Hexane fraction. For studying the effectiveness of N. Jatamansi total extract (NJTE) and its co-administration with ketamine (Ket.) in morphine induced tolerance, different groups of mice received morphine (3 mg/kg,ip), morphine (30mg/kg,ip) + Ket. (25, 50, 75 mg/kg,ip), morphine (30 mg/kg,ip) + NJTE (10,20,30 mg/kg,ip) or morphine (30mg/kg,ip) + Ket. (25 mg/kg,ip) + NJTE (10mg/kg, ip) for four days. Pretreatment was done 30 min before daily morphine administration. Tolerance was assessed by administration of morphine (9mg/kg, ip) and using hot-plate test on fifth day. The GC-MS analysis of the n-hexan fraction of total extract led to the identification and quantification of fifteen compounds, the main components were 9- Aristolen-1-alpha-ol (31.1%), Valerenal (31%) and Valerenic acid (26.5%). Pharmacological results showed that Ket. inhibited the development of morphine induced tolerance in the dose dependent manner although the maximum inhibition was observed at the dose of 20 mg/kg of NJTE. Co-administration of both drugs revealed synergistic effect. NJTE, Ket. and co-administration of both drugs significantly inhibited the development of morphine induced tolerance.

the purpose of this study was the evaluation of pharmaceutical properties and quality control of glucosamine preparations available in Iran drug market. 10 commercial products were selected and evaluated for some Pharmaceutical characteristics such as content uniformity, assay, weight variation and dissolution test. Dِetermination of glucosamine was performed according to a new high performance liquid chromatography (HPLC) method developed for the first time. The method was based on pre column derivatization of glucosamine by orthophthaldialdehyde (OPA). the results of these tests about 10 commercial products were as follow: assay was between 13. 69% and 138. 72%, for content uniformity RSD% was between 4. 17 and 26. 60, weight variation had RSD% between 0. 69 and 7. 5. Dissolved glucosamine (%) in dissolution test was between 20. 03% and 98. 71%. Similarity factor test on the results of dissolution test showed that at least 3 commercial products have not been in an acceptable range in comparison with reference product (No. 2). according to these results, good controls on the quality of food supplements are required.

Gene toxicology (particularly genocompatibility and/or toxicogenomics) has begun to be acknowledged as an important scientific discipline in drug delivery and targeting, in which the intrinsic genomic signature of chemicals and pharmaceuticals is going to be underlined in the heredity of living organisms for a better implementation of such pharmaceuticals. Viral and non-viral vectors are the two paradigms for transport of genome-based pharmaceuticals in vitro and in vivo. However, genomic impact(s) of these delivery systems in target cells/tissues are still in shed of their transfection potential. Despite substantial information on their cellular influence, little information is available about the genocompatibility and/or toxicogenomics of the non-viral vectors including cationic lipid (CL) delivery systems. In the current study, we investigated the genocompatibility of cationic lipid, Oligofectamine (OF) in human alvelolar epithelial A549 cell line. To screen the genomic impact(s) of these delivery systems, cytotoxicity assay using MTT and DNA microarray technology was utilized. RNA samples from treated (routinely used concentrations of CL) and untreated cells were converted to aminoallyl-cDNA, labeled with cyanine (Cy3/Cy5) and hybridized on target arrays housing 200 gene spots. Slid arrays were scanned, data was normalized and up- and down-regulated genes and their ontologies were detected. MTT assay showed cytotoxicity within A549 cells treated with the nanoliposomes. The gene expression profiles revealed marked changes (≥2-fold) in gene expression for 8-15% of genes from various genomic ontologies induced by OF. Among altered genes, some (e.g., il9r, ces111 and tnfsf6) were related to the apoptosis pathway; nevertheless the altered genes appeared to be within various gene ontologies. Our findings highlight pervasiveness of intrinsic genomic impacts by cationic nanoliposomes. Such impacts may interfere with the main goals of these delivery systems by masking/stimulating a cluster of non-specific genes that may affect the end point genotype and/or phenotype, thus we suggest genomic assessments for cationic liposome gene delivery systems.

There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drug for which topical and transdermal delivery is a viable option. Contraceptive drug-in-adhesive patches containing 17-β-estradiol and levonorgestrel were prepared using the acrylic type pressure sensitive adhesive (PSAs, DUROTAK2287) and the mixture of poly ethylene glycol citrate (PEG-CA), ethyl lactate (EL) and dimethyl sulfoxide (DMSO) as the chemical skin permeation enhancers. The enhancing effects of various enhancers with different concentrations on the permeation of 17-β-estradiol and levonorgestrel were evaluated using Frantz diffusion cells fitted with rat skin. The results showed that at the highest concentration of enhancers (2%) the rank order of enhancement effect for both drugs was PEG-CA/EL/DMSO 3/1/1 mixture> PEG-CA>EL>DMSO. In the presence of PEG-CA/EL/DMSO 3/1/1 mixture, the steady state flux for 17-β- estradiol and levonorgestrel were 0.455 ± 0.043μgcm-2h-1 and 1.416 ± 0.132 μgcm-2h- respectively. It was also shown that increasing the concentration of enhancer mixture led to reduction in the adhesion property of the PSAs. Dosage units were provided which transdermally deliver at least minimum daily doses of 17-β-estradiol and levonorgestrel for multiple days, such as for one week.

Several studies have indicated that co-administration of N-methyl-D-aspartate (NMDA) receptor antagonists could attenuate the development of morphine induced tolerance and dependence in mice. The aim of this study was to investigate the effects of selegiline (MAO-B inhibitor and NMDA receptor inhibitor) and amantadine (NMDA receptor antagonist and Dopaminergic system activator) or their co administration on tolerance (to analgesic effect) and withdrawal syndrome in mice. In different groups of mice morphine (50 mg/kg, ip) or morphine (50 mg/kg, ip) + selegiline (10, 20, 40 mg/kg, ip) or morphine (50 mg/kg, ip) + amantadine (20, 40, 80 mg/kg, ip) or morphine (50 mg/kg, ip) + amantadine (20 mg/kg, ip) + selegiline (10 mg/kg, ip) was administrated once a day for four days. The drugs (selegiline or amantadine) administered 30 minutes before daily administration of morphine (50 mg/kg, ip). Tolerance was assessed by administration of morphine (9 mg/kg, ip) and using hot plate test on fifth day. To investigate the withdrawal symptoms (jumping and standing on feet) in different groups morphine (50 mg/kg, ip) injected for 4 days. In the forth day half hour after the last injection, different doses of selegiline, amantadine or their co-administration were injected and after 1.5 hour later naloxone (5 mg/kg, ip) was injected and immediatly the withdrawal symptoms were detected during 30 minutes. The results showed that different doses of amantadine, increased the tolerance to analgesic effects of morphine significantly (P 0.001), withdrawal syndroms in the doses of 40 & 80 decreased significantly (P<0.01). But selegiline (10, 20, 40 mg/kg, ip) did not have a siginificant effect on the inhibition of tolerance and withdrawal syndromes. Co administration of selegiline and amantadine didn’t decrease the tolerance to morphine in hot plate test significantly. Conclution: It is concluded that, Probably amantadine in this study has a mechanism of activation of dopaminergic system in the administered doses. On the other hand selegiline potentiated adrenergic system with these doses.

Chrozophora tinctoria is naturally occurring annual plant, used as a dyeing substance and traditionaly it is used for the treatment of warts. In this study we attempt to evaluate the inhibitory effect of Chrozophora tinctoria on mouse skin tumors. Female Albino Swiss mice were divided in to different groups (each group 20 animals). Tumor initiation was achieved by a single topical application of 7, 12-Dimethylbenze (a) anthracene (DMBA) (40 μg/100 μl acetane/mouse). After 7 days, tumor promotion was begun by twice-weekly topical application of Benzoyl peroxide (BPO) (20 mg/300 μl acetone/mouse) for a period of 32 weeks. Also before 4 hours of DMBA application a group of animals received a single topical dose of chrozophora tinctoria extract (10 mg/gr carbopol gel/mouse). During this period, the animals were observed for tumor incidence. There were higher yields of tumors in those animals receiving both DMBA and BPO. However, the chrozophora tinctoria pretreated group showed complete inhibition of tumor incidence. The group of animals treated only with acetone, carbacol gel, DMBA, BPO and Chrozophora tinctoria alone did not develop any tumors during 32 weeks of observation. The results obtained from this study showed that chrozophora tinctoria inhibits completely Skin tumors, in comparison with the control group. Our results also indicated that chrozophora tinctoria extract probably through the scavenging of free radicals plays an important role in skin cancer inhibition. In conclusion, our data suggest that chrozophora tinctoria may be an effective chemopreventive agent and may act protective role against skin tumorigenesis. However, the exact mechanism of tumor inhibition by chrozophora tinctoria remains elusive and needs further experimentation.

Progesterone is a hormonal drug which its vaginal gel formulation because of low adverse effects nowadays has a vast use in menopausal and postmenopausal periods in the treatment of secondary amenorrhea and ART. It has more patient acceptance for the reason of ease in application and its once daily use. Unfortunately this product is not available in Iranian market. In world market, progesterone vaginal gel is marketed under the trade name of CRINONE and there are two forms 4% and 8%. First the solubility of progesterone in different solvents was evaluated, then formulations were prepared using gelling agent (Carbomer 934p), pH of the formulations was adjusted according to the pH of vagina. The stability of gels was evaluated in three different temperatures, refrigerator, room temperatures and 40°C oven. The in vitro release of drug was assessed using static diffusion cell and dialysis membrane. The concentration of drug was analyzed by means of UV spectrophotometer at 241 nm. Our findings showed that increasing the amount of gelling agent, decreased the drug release mean while decreasing the amount of paraffin and increasing the amount of glycerin increased the release of drug. Concomitant increasing of the amount of carbomer and glycerin didn’t change the release of drug. The results showed that release of drug follows zero order release mechanism. These findings show that bioadhesive polymers such as carbopol in the formulation prolonged contact, residence time and zero order release. ART = Assisted Reproductive Techniques.