Iranian Journal of Pharmaceutical Sciences

Lamotrigine is used in the treatment of CNS disorders, particularly epilepsy; pain; oedema; multiple sclerosis and psychiatric indications including bipolar disorder. Lamotrigine belongs to biopharmaceutical classification systems; BCS class II (Low solubility & High permeability). In addition, it requires immediate therapeutic action. Hence, the main objective of this study is to improve the solubility by solid dispersion technique and formulate it as oral disintegrating tablets (ODT) to avert the problems of swallowing and to provide rapid onset of action. Lamotrigine solid dispersion was prepared by using Tween 80 and Gelucire 44/14 as solubility enhancers and formulated it into ODT by direct compression technique using different concentrations of Kyron T-314, Kyron T-154, and Kyron T-104 as cross linked polymers. The tablets were evaluated for various parameters and the results were found to be satisfactory. The batches of LMTK314 (2), LMGK314 (2) were selected as optimized batch containing Kyron T-314 as super disintegrant in 2% concentration, as they showed 100% drug release in 8 minutes and 6 minutes with a disintegration time of 11 and 9 seconds respectively. Upon comparison of dissolution profiles of optimized formulae LMTK314 (2), LMGK314 (2) with a marketed product, it proved that the optimized formulae had shown better dissolution. The optimized formulations were subjected to stability studies for three months as per ICH guidelines and showed physical stability with insignificant change in the hardness, disintegration time, drug content and in vitro drug release.

Although the biokinetics, metabolism, and chemical toxicity of atorvastatin calcium are well known, until recently little attention was paid to the potential toxic effects of atorvastatin calcium on re-production and development in mammals. In recent years, it has been shown that atorvastatin calcium is a developmental toxicant given orally or subcutaneously (SC) to mice. Decreased fertility, embryo/fetal toxicity including teratogenicity, and reduced growth of the offspring have been observed following atorvastatin calcium exposure at different gestation periods. On the other hand, an in vitro study using fetal isolated mitochondria nowadays has been recognized as a confident tool to evaluate the developmental toxicity of a number of chemicals. Although the developmental toxicity induced by atorvastatin has been investigated, the precise cellular mechanism of atorvastatin -induced embryo-toxicity has not been thoroughly recognized yet. For investigating the effects of atorvastatin calcium on pregnant animals, three groups (control, sham and test) of NMRI mice were chosen. In test group,50mg/kg,100mg/kg and 150mg/kgof atorvastatin calcium were intraperitonealy administered at 11 day of gestation, in sham group only normal saline injected to interior peritoneum as indicated in the test group and in Control group which was considered as the comparison base line of our research, no injection was made. Caesarean sections were performed at 15 day of the gestation; and their placentas were examined externally. Based on our results atorvastatin calcium caused significant external anomalies, and caused a significant decrease (p<0.001) in the weight and diameter of placentas, the number of the embryos, their body weight and crown-rump length of fetuses.

Hydrogel-Based Metronidazole Bioadhesive Tablet (HMBT) was prepared as a novel vaginal delivery system to achieve Controlled release of drug from the tablet for vaginal candidiasis. The highly swollen hydrogel were prepared by dissolving chitosan in acetic acid solution containing drug, followed by neutralisation with sodium hydroxide and characterized by SEM, DSC and FT-IR and evaluated for % swelling. The drug loaded hydrogels were incorporated into tablet formulation by dry granulation method using bioadhesive polymers such as HPMC, sodium CMC and guar gum in different ratios. HMBT was tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release, bioadhesive strength, in vivo studies and antifungal activity. The FT-IR and DSC spectra’s revealed that there was no chemical interaction between drug and polymers used. SEM revealed that particles of hydrogels appeared small and irregular shaped with large numbers of pores. F3 formulation shows good in vitro release profile with highest bioadhesive strength. From the in vivo study in rabbit it was found that the HMBT hold the tablet for more than 12 hours inside the vaginal tube. It may be concluded from present study that HMBT can be used as a novel delivery system for local therapy of vaginal candidiasis which can controlled the release of drug for prolong period of time.

Lipoxygenase (LOX) catalyzes irreversible transfer of oxygen molecule to Arachidonic and Linoleic acid to produce 13 Hydroproxy Octadecadienoic acid. Recent studies showed that the involvement of Lipoxygenase products, leukotrienes, in inflammations and Lipoxygenase pathways acts as mediators of early inflammatory events in atherosclerosis. The aim of the present study is purification and characterization of Lipoxigenase from Human placental.For this aim, the human placental Lipoxigenase was extracted and purified by normal butanol, acetone, ammonium sulphate (30-80%), and gel permeation chromatography on Sephadex G-150. After purification and characterization of LOX, the in vitro inhibitory effect of KCN, NaN3 and some selected bivalent ions such as Co2+, Ni2+, Cu2+, and Zn2+ were checked on the activity of purified LOX. Results showed that specific activity was 123.16 u/mg proteins and the yield of purification was 21.84 percent. Also, it was found that Co2+, Ni2+, KCN, and NaN3 at concentration of 20 mM had inhibitory effect on LOX activity and their inhibitory was 72.4, 58.2, 56.5 and 42.3% respectively. However, Cu2+ stimulated the lipoxygenase activity at the same concentration whereas Zn2+ has no significant effect on LOX activity. With respect to increase of LOX activity in the patient with cardiovascular diseases, Alzheimer disease, cancer, chronic obstructive pulmonary disease (COPD), artherogenesis, and also airway inflammation diseases, suggesting that LOX inhibition may have beneficial effects as a potential target to limit the severity of related symptoms of these diseases and therefore these inhibitors could be considered as an agent for decreasing the enzyme activity in association with the disease.

Herbal water is referred to the liquid obtained from the distillation of medicinal plants. Different parts of plants, such as flowers, fruits, leaves, seeds and roots have long been used to produce herbal waters. Herbal waters are used as dietary supplements and alternative medicine and are commonly used for flavoring in baking. Previous studies focused on the non-volatile constituents of herbs. However, plants also contain numerous volatile chemicals. Therefore, antioxidant capacities of 20 Iranian herbal waters were assessed by FRAP, DPPH and TEAC assays, and their total phenolic contents measured by Folin–Ciocalteu assay. These herbal waters exhibited a broad range of antioxidant activities, varying from 0.18 to 3.20 mmol Fe2+/l in the FRAP assay, 91.43-94.99% inhibition in the DPPH assay, 19.27-28.79 mg trolox equivalent/ml in the TEAC assay and 2.90-132.51 mg gallic acid equivalent/l in total phenolic content. Classification of Iranian herbal water was performed by cluster analysis and principal component analysis and four groups were recognized based on antioxidant activity and total phenolic content. Rose, thyme, summer savory and mint herbal waters were screened as the highest antioxidant activity and total phenolic content.

Stock return is usually considered to be affected by firm’s financial ratios as well as economic variables. Fundamental method assume that stock returns is not solely related to the stock market. Most result come from the company condition, industry situation and whole economy. In this paper, this relationship between stock return and fundamentals is studied using the data for 22 pharmaceutical companies in Tehran Stock Exchange over a 7 year period, and effective factors on stock return are investigated. Because of our data natural we used panel data model from econometric methods.The results show that 80 pecent of change in stock return can be explained with 9 fundamental variables factors including debt-equity ratio, working capital to total asset, current ratio, net profit margin, operating cycle, market share, inflation rate of medicinal products prices, total asset, and exchange rate have significant effect on stock return. This factors can be used in decision making in pharmaceutical industry.

Petroselinum crispum belongs to the Apiaceae family, is a well-known spice and vegetable. The essential oil obtained from the fruit has also strong action on the central nervous system. Present study is designed to evaluate the phytochemical screening, antibacterial and cytotoxic activity of the leaves of Petroselinum crispum collected from Oman. Results of phytochemical screening indicate the presence of primary and secondary metabolites. Antimicrobial activity was measured using disc diffusion method against S.aureus,E.coli, P.aeruginosa and K. pneumonia. Brine shrimp test was used to estimate cytotoxic activity. In antibacterial assay, Petroselinum crispum leaves extracts showed very strong results, inhibition zones ranged from 7 – 20 mm. So this plant can be used as a good source of potential antimicrobial agent. Hydro alcoholic and Petroleum ether extracts showed the highest antibacterial activity. Furthermore, Ethyl acetate and Hydro alcoholic extracts have almost killed 90% of the shrimp larvae at higher concentration of 1000 μg/ml. LC50 values for the two extracts was 51.95 and 88.15μg/ml, respectively. Non polar fractions like chloroform extract have displayed low cytotoxic activities as compare to polar extracts.

Methyl indole derivative of some 6-aryl-4,5-dihydropyridazin-3(2H)-ones (3a-e) were synthesized by Mannich reaction and evaluated as anticonvulsant against MES (50mA, for 2sec), INH (250mg/kg), scPTZ (80mg/kg) and STR (3mg/kg) induced convulsion methods at 50 mg/kg dose level. All compounds 3a-e were also evaluated as antitubercular agent against M. tuberculosis H37Rv by MABA method. All compounds 3a-e showed anticonvulsant activities against MES, INH and scPTZ-induced convulsions methods but no compounds were active against STR-induced method. Compound 3b, compound 3d and 3e showed highest protection against MES, INH and scPTZ-induced convulsion models respectively. Compound 3d showed highest antitubercular activity, with 12.5μg/ml MIC value. Previous data reported that the pyridazinones are the important biological compounds which possess almost all types of biological activities. Due to this reason, we synthesized some pyridazinone compounds and characterized them by spectral analysis. Results indicated that title compounds showed moderate to good anticonvulsant activities but less antitubercular activity.