DARU, Journal of Pharmaceutical Sciences
Volume:15 Issue: 2, Summer 2007

This study describes the feasibility of transdermal controlled administration of Losartan potassium (LP) across human cadaver skin. Study also defines the influence of capsaicin, sex and site of application on permeation characteristics and determined an appropriate animal model for human skin permeability. The permeation of LP of various formulations was studied using Keshary-Chein diffusion cell. Optimized controlled formulation (without capsaicin) released 42.17% (±1.85) of LP in 12 hr whereas treatment formulation (with capsaicin 0.028 % w/v) released 48.94% (±1.71) of LP with significant difference on null hypothesis. Influence of sex showed statistically significant difference for permeation of LP through male and female rats, as well as male and female mice across both the abdominal and dorsal sides of the skin (p<0.05). Similarly statistically significant differences were noted for permeation of LP across male and female mice abdomen-dorsal, but not for male rat abdomen-dorsal and female rat abdomen-dorsal. Furthermore, in-vitro permeation of LP across human skin was compared with the permeation across rat and mice skins. Male rat and male mice dorsal skin was found to have closer permeability characteristics to human than other skin membranes, but the Factor of Difference values were < 3 for all membranes which were used suggesting the membranes are good models for human skin permeability. In conclusion simple transdermal adhesive patches formulations incorporating high molecular weight of LP can deliver a dose in-vivo and proposed model skin membranes can be utilized for future pharmacokineic and toxicokinetic studies as well as metabolism studies of LP

Cationic liposomes are used for cellular delivery of antisense oligodeoxynucleotide (AsODN), where release of encapsulated AsODN is mainly controlled by endocytosis and fusion mechanisms. In this investigation, it was tried to model such a release process that is difficult to evaluate in cell culture. For this purpose, an AsODN model (against protein kinase C-α) was encapsulated in a DODAP-containing cationic liposome and evaluated for size, zeta-potential, encapsulation and ODN stability. Vesicular models of outer layer and total plasma membranes and early and late endosomal membranes were developed, based on lipid content and pH, using ether injection method. ODN release was determined by the fluorescence dequenching of encapsulated FITC-ODN. Zeta potential, size and ODN encapsulation efficiency of the prepared liposomes were -2.49 ± 7.15 mV, 108.4 nm and 73% respectively. ODN protection was 3-4 times more than that of conventional liposome/ODN complexation method. There was a correlation between model concentration and percent of ODN release. At 7.5 µM, the percent of released ODN was 76% for the cholesterol-free model of the late endosome and 16% for the early endosomal membrane; while the release was less than 11% for the models of plasma membrane. ODN release increased with temperature in the range of 4-37◦C for the late endosomal model, but not for others, possibly due to their high cholesterol contents or acidic pH. The interaction was fast and completed within 5 minutes and didn’t change in the range of 5-60 minutes. Our data are in agreement with published cell culture studies and reveal that cell-liposomes interaction can be modeled by lamellar membranes.

An extended-release osmotic dosage form was designed and the effect of β-cyclodextrin (BCD) inclusion complexation on the solubility of lovastatin in aqueous media was investigated. The lovastatin BCD solid systems were prepared by kneading method. The elementary osmotic pumps (EOPs) were prepared with lovastatin BCD complex with cellulose acetate (CA) and polyethylene glycol as plasticizer. The effect of the BCD molar ratio on enhancement of lovastatin dissolution rate and the influences of various parameters (e.g. drug –BCD ratio, molecular weight and amount of PVP, coating weight gain) on drug release profiles were investigated. The solubility and dissolution rates of lovastatin were significantly increased by using inclusion complexation. It was found that PVP K90 was a suitable hydrophilic polymer with thickening effect and had profoundly positive effect on drug release. The present results confirmed that dissolution rate of lovastatin BCD were greatly enhanced and this system has suitable solubility behavior in EOP tablet formulations.

Salvia bracteata is a permanent herb which belongs to Lamiaceae family and grows wildely in the west of Iran. In this study the composition of the essential oils of aerial parts of Salvia bracteata in different growth stages were analysed and compared. The oils were obtained by hydrodistillation and analyzed by GC and GC/MS. The oils had high amounts of monoterpene compounds, with α-pinene, limonene, myrecene and β-pinene as major components in different growth stages.

The free radical scavenging capacity, reducing power and inhibition of β–carotene peroxidation of Phlomis persica (PP) extracts was investigated. In addition, the effect of this extract on reduction of the hydrogen peroxide-induced cytotoxicity in non-immortalized fibroblast was examined. The extracts showed free radical scavenging capacity, and the ethyl acetate extract showed marked effect on inhibition of lipid peroxidation similar to that of gallic acid. These results were further supported by a protective effect of Phlomis crude extract on H2O2-induced cytotoxicity in human non-immortalized fibroblasts.

Several novel 2-amino-5-[4-chloro-2-(2-chlorophenoxy)phenyl]-1,3,4-thiadiazole derivatives 4a-d were synthesized and their anticonvulsant activity was determined by evaluation of the ability of theses compounds to protect mice against convulsion induced by a lethal doses of pentylentetrazole (PTZ) and maximal electroshock (MES). The result of anticonvulsant data shows that among the synthesized compounds, 5-[4-chloro-2-(2-chlorophenoxy)phenyl]-N-ethyl-1,3,4-thiadiazol-2-amine 4c was the most active compound in both MES and PTZ tests with an ED50 of 20.11 and 35.33 mg/kg, respectively.

Widespread uses of fluoroquinolones have resulted in increasing incidences of resistance against these agents all over the world. The aim of this study was to assess, susceptibility of Escherichia coli strains from patients with Urinary Tract Infection against common fluoroquinolones and detection of mutations in the gyrA gene. Antimicrobial susceptibility testing of 164 E.coli isolates from patients with UTI, was evaluated by disk agar diffusion (DAD) and MIC methods. Polymerase chain reaction of E.coli strains were performed by amplification of Quinolone Resistance Determining Region (QRDR) of gyrA gene. PCR products were tested by Conformational Sensitive Gel Electrophoresis (CSGE) and those with hetrodublexes were selected and examined by DNA sequencing. According to disc agar diffusion, 49.3% were resistant to nalidixic acid, 41.4% to norfloxacin, 44.5% to ofloxacin and 40.2 % to ciprofloxacin. By Minimal Inhibitory Concentration (MIC) testing a high-level of resistance (42.1%) to ciprofloxacin was observed. Mutations in codons 83 and 87 in all 81 isolates were positive by CSGE method.

Chlamydia trachomatis (CT) is the most common cause of sexually transmitted infections (STI) worldwide and its early detection and treatment can reduces the high morbidity associated with this infection. In this study a sensitive diagnostic polymerase chain reaction (PCR)-based enzyme immunoassay (PCR-EIA) method was developed which detects CT in women with cervicitis. Endocervical swabs collected from 123 women (20-55 years) with cervicitis were tested by both conventional PCR, and PCR-EIA assays, using identical sets of primers to amplify a CT-specific plasmid. For the conventional PCR, amplicons were detected by agarose gel electrophoretic analysis and the PCR-EIA assay used biotin-labeled primers, strepavidin-coated plates, a digoxigenin-labeled probe, and a final enzyme-linked colorometric analysis (405 nm) was used to measure the CT amplicon. The frequency of positive CT infection by conventional PCR and PCR-EIA assay was 7% and 17%, respectively. The highest frequencies of CT infection were among women of 31-40 years old group (25%). The PCR-EIA limit of detection, calculated by linear regression analysis, was10 pg of CT DNA (r2=0.9642). The degree of agreement (Kappa) between the conventional PCR and PCR-EIA method was 0.556 (p<0.0001).

There is growing interest for beneficial effect of Mg in the cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extracellular or intracellular concentrations of Mg. The aim of present study was to investigate the preconditioning effects of magnesium (Mg) on cardiac function and infarct size in the globally ischemic-reperfusion in isolated rat heart. Rat hearts were Langendorff-perfused, subjected to 30 minutes of global ischemia and 90 minutes of reperfusion, and assigned to one of the following treatment groups with 7 hearts in each group: (1) control, (2) ischemic- reperfusion, (IR), (3) ischemic preconditioning, (IPC) of 5 minutes of global ischemia - reperfusion before lethal ischemia; or pretreatment with (4) 30 µmol/L of Diazoxide (Dia), (5) 8 mmol/L magnesium, (6) 10 µmol/L glibenclamid (Gli), (7) magnesium and Dia and (8) magnesium and Gli. Infarct size was measured by the triphenyltetrazolium chloride method. Left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate and coronary flow (CF). Mg limited infarct size (9.76 % vs 44.47% in IR, P< 0.001) as did Dia (10.2 % vs 44.4 % in IR P< 0.001) and IPC (8.69 % vs 44.47% in IR, P< 0.001). The protective effect of magnesium was abolished by Gli. Administration of Mg had an anti-infarct effect in ischemic-reperfusion isolated rat hearts and improved cardiac function. Blockade of K-ATP channel abolished the protective effects of magnesium and suggest that K-ATP channel has an important role in this effects.

Metformin is often prescribed for glycemic control in type II diabetes mellitus. This drug is the first line treatment for obese without renal or liver failure. Different pharmaceutical types of Metformin are available. As a clinical trial, therapeutic effects of a generic (Aria Pharmaceutical Company, Iran) with a brand metformin (Glucophage, product of Merck pharmaceutical company, France) in diabetic patients were compared. This double blind randomized clinical trial study was performed in 60 non-pregnant diabetic patients in order to compare therapeutic effects of combination therapy (Glibenclamide - Metformin "Generic or Brand" a 12-week period). Patients were evaluated for FBS, BS2hpp, HbA1C, lipid profile, liver function tests, weight, BMI, and side effects. Both pharmaceutical types of Metformin had the same therapeutic effects for controlling of glycemia, and lipid profile and weight, between two groups statistically were not significantly different. GI discomfort (distention) was the most common side effects of both drugs (33%). There were no significant statistical differences between these two products regarding their side effects and 70% of patients were satisfied by taking each kind of product. On the basis of results, while both products had comparable efficacy, the generic product which is a domestic product and easier for patients to have access to it showed fewer side effects.