Iranian Journal of Pharmaceutical Research
Volume:5 Issue: 4, Autumn 2006

Meloxicam is a poorly water soluble non steroidal anti-inflammatory drug and antipyretic agent. The aim of the present work was to investigate the effect of different types of carriers on in vitro dissolution of meloxicam. Meloxicam solid dispersions were prepared by physical mixing, co-grinding and solvent evaporation methods with polyethylene glycol (PEG) 6000. The effect of solubilization by sodium lauryl sulphate (SLS) was also studied. The dissolution was determined by USP XXVII Apparatus I, using phosphate buffer with a pH of 7.4 as the dissolution medium. The maximum in vitro dissolution of meloxicam, i.e. 97.45% in 60 min, was observed for solid dispersions containing meloxicam (150 mg), PEG 6000 (350 mg) and SLS (75 mg) prepared by solvent evaporation method containing a sum of 3 g of Lactose and MCC (4:1) as additives. The general trend indicated that there was an increase in dissolution rate for solid dispersions containing the solubilizer SLS. The best-fit model indicating the mechanism of dissolution from the formulation showing the highest release for was found to be Higuchi matrix release (r=0.9774, b=13.042, a=2.4798). Infra red spectroscopy (IR) indicated that meloxicam in solid dispersions showed physical entrapment. The increased in dissolution rate of meloxicam by solid dispersion technique may be due to increase wettability and hydrophilic nature of carrier.

Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, undergoes photo-degradation to dehydro-nifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydro-nifedipine (NDNIF) when exposed to sunlight or some kinds of artificial lights. NIF photo-degradation products do not contribute to clinical activity, thus prevention of photo-degradation of NIF formulations is very important. Large differences in photo-stability between bioequivalent NIF products could potentially result in the therapeutic failure of unstable preparations. The aim of this study was to evaluate the effect of microencapsulation on nifedipine photo-stability. Four different microspheres of nifedipine were prepared using ethyl cellulose, ethyl cellulose plus titanium oxide, pectin and gelatin. Microspheres were exposed to fluorescent light and the content of NIF, DNIF and NDNIF for each product was measured using a specific and sensitive reversed phase high-pressure liquid chromatography (HPLC) method to determine the extent of photo-decomposition. In addition, photo-degradation of pure NIF powder was compared with acidic and buffer solution of NIF. Solution of NIF degraded in one day, while microencapsulation of NIF prevented the photo-degradation for up to six days against light exposure. Therefore, it may be concluded that present microencapsulation method without using other compounds such as opaque materials do not provide enough protection

The use of proteins and peptides as human therapeutics has been increased in recent years. Lipase is a relatively homogeneous proteinaceous enzyme indicated in maldigestion. The purpose of the present study was to evaluate the effect of humidity along with compactional pressure on the enzymatic activity of wheat germ lipase.Samples of lipase powder were kept at different relative humidity (RH) conditions (24, 40, 63 and 75 %) before compaction under various pressures (74-372 Mega pascal or Mpa). The relative enzymatic activity of the compacts was then determined by titration method using Triacetin as substrate. Density measurements were also conducted in order to describe the possible mechanism of the enzymatic activity. The results indicated densities of the compacts prepared under various compactional pressures increase as humidity rises. Based on the results, activity loss of the compacts following relative humidity increase can be related to steric hindrance caused by higher pressures. However, there was no significant difference between densities at different compactional pressures at a given humidity condition.

Some new 3-[(5-benzylidene-2-phenyl)-3, 5-dihydro-4-H-imidazol-4-one-3-(4-bezoylhydrazono)]-indole-2-ones (VIII) have been synthesized from different isatinhydrazones (II) by condensing with 2-phenyl-5-benzylidene- 3-N (4-acetyl phenyl)-1, 5-dihydro-imidazol-4-one (VII). Their chemical structures have been confirmed by IR, 1HNMR, MASS and by elemental analysis. Investigation of antimicrobial activity of compounds was done by the disk diffusion technique. Among the compounds tested, the compound with 5-Br substitution showed the most favourable antimicrobial activity.

The aim of the present study was to investigate whether and by which mechanism; histamine can induce state-dependent retrieval of passive avoidance task. The pre-training or pre-test intracerebroventricular (i.c.v.) injection of histamine (20µg/mouse) impaired retrieval, when it was tested 24 h later. In the animals, which retrieval was impaired due to histamine pre-training administration, pre-test administration of histamine, with the same dose, restored retrieval. The H1 blocker, pyrilamine (20 µg/mouse, i.c.v.), but not the H2 blocker; ranitidine prevented the restoration of retrieval by pre-test histamine. A pre-test administration of histamine H3 receptor antagonist, clobenprobit, also reversed hitamine-induced impairment of memory retention. In conclusion, histamine can induce state-dependent retrieval through the H1 receptor H1 mechanism.

Chronic exposure to lead (Pb) affects neural functions in central nervous system (CNS) particularly the learning and memory. On the other hand, alteration of calcium level in the CNS results in activation of NOS. It has been shown that lead enters the neurons through calcium channels and displaces Ca2+ from calcium binding proteins such as calmodulin and troponin C thereby affecting calcium-mediated processes.Our recently data showed that no prodaction due to NMDA receptor simulation in cultured CA1 pyramidal cells has been diminished in the presence of 10 nM of Lead acetate. Therefore, it is possible that Lead can inhibit the elevation of NO through blockade of NMDA receptor and interference of LTP through this mechanism. This finding may attribute to the effect of lead on the NOS activity or expression as key enzyme producing NO. In this study we have examined the effect of lead acetate on the NOS expression in the presence of NMDA agonist using immunocytochemical analysis. Expression of nNOS were examined in the CA1 pyramidal cells exposed to 10 and 100 nM lead acetate and 40 μM ACBD (NMDA agonist). The result of this experiment showed that the enhanced nNOS expression induced by ACBD significantly diminished by lead acetate. The trend of this inhibition is similar to amount of NO production indicating that the decrease of expression may major reason of decrease in NO production.

CYP3A4 probably has the broadest catalytic activity of any cytochrome P450. It is a crucial task to test new drug candidates in a reliable system for their ability to induce expression of this enzyme. Firstly, a total of 300 bp core distal enhancer of CYP3A4 XREM region (-7972/-7673) were amplified from human genomic DNA. The PCR product was then ligated into a human secretory alkaline phosphatase cDNA-containing reporter vector (pSEAP2-1) creating pX-SEAP2 plasmid. Secondly, 1143 bp of the CYP3A4 proximal promoter region (-1203/-61) was amplified from the genomic DNA and then ligated into pX-SEAP2 plasmid DNA (between XREM and alkaline phosphatase gene), creating pXP-SEAP2 plasmid. Reporter constructs were then co-transfected with an hPXR expression vector into human liver and intestinal cells in culture. Xenobiotic modulation of CYP3A4 promoter activity was determined by chemiluminescent secretory alkaline phosphatase assay. Significant CYP3A4 induction at the transcriptional level using three different cell lines and four classical CYP3A4 inducers was observed. Transfection of reporter constructs in HepG2, HuH7 and Caco-2 cells, in general, produced similar pattern of induction by the same drugs with the exception ofphenobarbital. The results suggest that, carefully designed reporter gene systems can provide a useful in vitro approach for characterization of possible CYP3A4 inducers.

Vitamin C, an antioxidant substance soluble in water, can react with amino groups of proteins to form schiff bases. As diabetes leads to glycation of various protein which has effect on structure and biochemical activity of them, the inhibition of this process seems very vital. For several years researches in this field have done their best to recognize the antidiabetics compounds.The aim of this study is to determine the effects of vitamin C on albumin glycation in vitro. So in the presence of various concentration of vitamin C, albumin was glycated and evaluating using TBA method.The results showed that vitamin C is statistically significant (P<0.05) inhibit or decrease the reaction of albumin glycation. The findings of this research showed that vitamin C probably inhibit the reaction of glycation in decreasing complications occurring in diabetes.

Seed oils of Passiflora edulis, Jatropa curucas, Tinospora cordifolia, Sesbania grandiflora and Sapindus laurifolia were investigated for their antihelmintic property against Pheritima pasthuma. Three concentrations (10, 50 and 100 mg/ml) of each oil were studied in the bioassay, which involved the determination of time of paralysis and time of death of the worm. Sesbania grandiflora showed the highly significant antihelmintic activity in both the parameters (paralysis and death), while Tinospora cordifolia showed significant effect in case of time of death. Piperazine citrate (10 mg/ml) was included in the assay as standard reference drug.

The present study was undertaken to investigate the effectiveness of the ethanolic extract of Echinophora platyloba DC. on Candida albicans.Using the agar dilution method, the growth condition of standard Candida albicans ATCC 10231, cultured on the media containing plant extracts at different concentrations (1,2,4,8,16,32,64,128 and 256 mg/ml) was studied. The results were recorded twenty one days after the incubation period, maximum time for the growth of fungi.Results showed that the extract of Echinophora platyloba, equal or above the concentration of 2mg/ml, effectively inhibits the growth of Candida albicans. In other words it shows growth on media containing 1mg/ml of the extract. Results of the present study revealed a great promise in the application of Echinophora platyloba extract against Candida albicans. It is concluded that the plant studied could be a good antifungal source.