Iranian Journal of Pharmaceutical Research
Volume:6 Issue: 4, Autumn 2007

Hydrophobic grade fumed silicas are generally used in tabletting as lubricants. They are also found to retard the release of pharmaceutical actives. This is because of their hydrophobic nature, which gives good cohesive and adhesive properties. considering this point it was thought that they could be used as dry coating agents for solid dosages forms. The model drug selected for this work was paracetamol in granular form and the various coating materials evaluated were hydrophobic grade fumed silicas such as Wacker HDK H-20, Wacker HDK H-15 and Aerosil R-972. Aerosil R-972 was found to be satisfactory and extended the release process up to 8 h at concentrations as low as 0.75%. Key parameters such as coating, mixing duration, rotation speed in dissolution test, and medium composition were studied, which were shown not to alter the release significantly.

Preformulation studies on transdermal dosage forms involve liberal use of animal skin for assessing the permeation characteristics of drugs, influence of permeation enhancers, optimizing the formulation variables etc. The restricted availability of animal skin due to concerns regarding prevention of cruelty to animals has generated considerable interest in developing polymeric films for use as skin substitute during in vitro permeation experiments. The present investigation aimed at preparing films containing different ratios of chitosan (CH) to chondroitin sulphate (CS) and rigidizing them by dipping in sodium tripolyphosphate (NaTPP) solution. Statistical optimization designs were employed to screen and optimize the active process and formulation variables that significantly influenced the in vitro permeation of 5-fluorouracil (5-FU) and indomethacin (INDO), model polar and non-polar drugs, respectively, across these polyelectric composite (PEC) films. CH to CS ratio, concentration of NaTPP and rigidization time was found to significantly influence the in vitro permeation of both drugs. The presence of both sulfonate and phosphonate linkages in PEC films rigidized by 2% w/v NaTPP allowed lowest permeation of either drug. However, films rigidized by 2.5% w/v NaTPP retained predominantly phosphonate linkages and were highly permeable to both drugs. The in vitro permeation of both drugs across optimized film formulations was not found to be significantly (p<0.05) different as compared to that across rat, rabbit and human epidermal sheets. The optimized PEC films have a great potential to be developed as substitute of animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.

The descriptors computed by HyperChem® software were employed to represent the solubility of 40 drug molecules in supercritical carbon dioxide using an artificial neural network with the architecture of 15-4-1. The accuracy of the proposed method was evaluated by computing average of absolute error (AE) of calculated and experimental logarithm of solubilities. The AE (±SD) of data sets was 0.4 (±0.3) when all data points were used as training set and the solubilities were back-calculated. The AE for predicted solubilities using a trained network employing 1/3 of data points from each set was 0.4 (±0.3) and this finding reveals that the network is well trained using a limited number of experimental data. To provide a full predictive method, data sets were divided into two sets and the network was trained using 20 data sets and the next 20 sets were used as prediction sets. The produced average AEs (±SD) were 1.7 (±1.1) and 1.6 (±1.5), for two sets of analyses. In these analyses, only the computational descriptors, temperature and pressure ofSC-CO2 were used and no experimental solubility data is employed.

Synthesis of 2-[2-(2,6-dichlorophenyl)amino]phenylmethyl-3-[4-(2-substitutedphenyl-4-oxo-thiazolidinyl)aryl]-6-bromo quinazolin-4(3H)ones VIa-j have been achieved from the starting material 2-[(2,6-dichlorophenyl)amino] phenylacetic acid I to benzoxazine III, Further reaction with p-phenylindiamine and substituted aromatic aldehyde gave 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-3-(4-aminoaryl)-6-bromo quinazolin-4(3H)-ones IV and 2-[2-(2,6-dichlorophenyl)amino]phenylmethyl-3-[4-(2-substituted arylidene)aryl]-6-bromo quinazolin-4(3H)ones Va-j respectively. Va-j on cyclization with thioglycolic acid gave VIa-j. All the synthesized compounds have been characterized on the basis of elemental analysis, IR and 1H-NMR spectral data. They were screened for antibacterial and antifungal activity at two concentrations and compared with the standard drugs penicillin-G, ampicillin, and amoxicillin. The compounds containing 4-OCH3 and 3, 4, 5-(OCH3)3 showed good activity, compared with the standard drugs.

The affinity of low density lipoprotein(LDL) to its receptor is very important, because most of LDL-uptake pathway is done by the LDL receptor and the change in size of LDL particle and the modification in its components may affect the LDL affinity for its receptor.In this study, the effects of a powerful lipid-soluble antioxidant “ubiquinol-10” have been investigated on the affinity of LDL to its receptor. LDL receptor was purified of bovine adrenal tissue. LDL was isolated by sequential density ultracentrifugation from normolipidemic human plasma. Then, LDL was labeled with fluoresein isothiocyanate (FITC) at 4°C for 24 h. Native LDL was incubated with various concentrations of ubiquinol-10 for 2 h. Finally, native LDL(treated with ubiquinol-10) was incubatd with the LDL receptor in the presence of labeled-LDL at 37°C for 30 min. After incubation, the medium was centrifuged at 4000×g for 20 min and the fluorescence intensity(FI) of supernatant from each sample was determined at excitation=495 nm and emission=515 nm. The elevation of FI in each fraction demonstrates increasing the affinity of non-labeled-LDL to its receptor.Our results showed that ubiquinol-10 increased the affinity of LDL to its receptor, and at the concentration of 200 µM it had the greatest effect.These finding raise the possibility that ubiquinol-10 may decrease the effect of LDL in formation of atherosclerotic lesions.

Nonenzymatic glycation of low density lipoprotein (LDL) is a reaction of glucose and other reducing sugars with apolipoprotein B100 (apo-B100) lysine residues. In diabetes, this reaction is greatly accelerated and is important in the pathogenesis of diabetic complications. The objective of this study was to investigate in vitro effects of α-tocopherol, ascorbic acid and lycopene on LDL glycation. LDL was isolated from EDTA-plasma by ultracentrifugation using a single step discontinuous gradient. LDL and glucose were incubated without and with different concentrations of lycopene, ascorbic acid and α-tocopherol. LDL glycation were estimated by sodium periodate assay. Based on this study results, α-tocopherol, ascorbic acid and lycopene decrease LDL glycation in a dose dependent manner. The electrophoretic mobility of glycated LDL decreased in presence these nutrients. These effects may be due to antioxidant properties of these nutrients and may have a role in ameliorating atherosclerotic risk of patients with diabetes mellitus.

The effects of therapeutic doses of dillsun, garsin, antum and statins on rat liver cytosolic phosphatidate phosphohydrolase (PAP) activity, a key enzyme in triacylglycerol synthesis, and on serum and liver lipids were examined. Lovastatin and simvastatin both stimulated the enzyme activity by 29% and 43%, respectively. The stimulatory effects were dose-dependent and accompanied by the decline in triacylglycerol and cholesterol concentrations of serum (20-29%) and liver (12-29%) suggesting a possible feed-back mechanism for PAP control. Dillsun (0.5-2 ml/day) did not affect PAP activity and liver lipids but lowered serum triacylglycerol (27%) and cholesterol (20%) concentrations at a dose of 2 ml/day. Antum administration also showed similar pattern as dillsun except that it caused a decrease in the liver lipids as well. Garsin (250-1000 mg/Kg) inhibited PAP activity (14-22%) with simultanous decrease in the liver and serum lipids; maximum decrease in serum triacylglycerol and cholesterol were 14% and 21%, respectively. The data demonstrated that the antilipidemic drugs tested exert their effects, at least in part, through alteration of hepatic PAP activity.

Metronidazole and it’s derivatives are drugs that have both antiprotozoal and anti bacterial effect.The reproductive toxicity of metronidazole has been shown in some studies. To investigate the effect of metronidazole on spermatogenesis in adult male rats, this study was designed.Eighteen wistar male rats (70-90days old) were randomly divided into three groups. Animals in group I (Control group) were administered the water. Animals in groups II, III were administered metronidazole at doses of 200 and 400 mg/kg/day for 60 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), luteiniging hormone (LH), testosterone assessment. In the 200 and 400 mg/kg groups, there were significant decreases in the testes and accessory sex organ weights, plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII.It is concluded that metronidazole has a suppressive influence on spermatogenesis and sex hormones in rats.

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Capparis spinosa (Capparidaceae) to treat hepatic diseases. Protective action of C. spinosa ethanolic root bark extract was evaluated in this study in an animal model of hepatotoxicity, which was induced by carbon tetrachloride.Healthy male mice (30-35 g body weight, 6-8 week old) were divided into 7 groups. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCl4; Group 3 was administered olive oil (vehicle); Groups 4-6 received different doses of ethanolic root bark extract (100, 200 & 400 mg/kg) with CCl4; Group 7 was administered overdose of the extract (800 mg/kg). The parameters studied were alanine transaminase and aspartate transaminase activities and duration of sleep. The hepatoprotective activity was also supported by histopathological studies of liver tissue.Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum enzyme activities, reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with ethanolic root bark extracts showed significant decrease in the levels of serum markers, indicating the protection of hepatic cells. The results revealed that ethanolic root bark extract of C. spinosa could afford significant dose-dependent protection against CCl4 induced hepatocellular injury.

The roots and rhizomes of Tanacetum parthenium (L.) Schulz. Bip. (Asteraceae), have been used in Iranian traditional medicine under the name of Aqhovan, as digestive and stomachic tonic. Composition of the essential oil, which was obtained from the root of T. parthenium collected from Karaj, was determined by gas chromatography, combined GC/MS and GC/IR. In total, 20 components (92% of essential oil) were identified. Major constituents were camphor (30.2%), (Z)- chrysanthenyl acetate (26.5%), α-farnesene (11.1%) and spathulenol (8.2%).

Since there is no detailed hospital based incident reporting system, this study was designed to evaluate the medication errors associated with infusion pumps in intensive care unit (ICU). The investigation was conducted in a Teaching hospital in the form of a prospective, observational study. A sample size of 43 doses administered to ICU patients was chosen to enable reliable estimate of error rates. Any deviation in the IV pumps implication from the guidelines and/or doctor’s order in the charts was measured as the main outcome. Forty three doses with 258 opportunities for error were observed. Twenty (7.8%) errors were detected, of which 14 (20%) were incorrect dose, 4 (20%) labeling error, 2 (10%) unauthorized medication. From incorrect doses, 8 (57%) resulted in overdose. Benzodiazepines were the most common class of drug involved. We concluded that regarding the infusion pump usage for drug delivery, a large number of errors exist.