Iranian Journal of Pharmaceutical Research
Volume:9 Issue: 2, Spring 2010

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of a highly water/soluble drug, salbutamol sulphate by (water in oil) in oil emulsion technique using ethyl cellulose as the retardant material. Various processing and formulation parameters such as drug/polymer ratio, stirring speed, volume of processing medium were optimized to maximize the entrapment. The release of salbutamol sulphate from ethyl cellulose microsphere was compared and possible release mechanism proposed. Microspheres were prepared by water in oil emulsion technique using acetonitrile/dichloromethane (1:1 ratio) solvent system. Span 80 was used as the dispersing agent and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well as compatibility by infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffractometry and scanning electron microscopy (SEM). The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 55.7 - 76.6 % of entrapment and release was extended up to 10 h. Various processing and formulation parameters such as drug/polymer ratio, stirring speed, volume of processing medium, etc. significantly affect the drug release from the microspheres. The best/fit release kinetics was achieved with Higuchi plot followed by zero order and first order. The release of salbutamol sulphate was influenced by altering the drug to polymer ratio and the drug release was found to be diffusion controlled.

The aim of this study was preparation and evaluation of ciprofloxacin-containing minitablets for ocular use, in an attempt to obtain prolonged and controlled drug release to the anterior eye segment.Following initial studies on ciprofloxacin powder, it was formulated into ocular minitablets. For this purpose, ciprofloxacin along with various amounts of different sustained release cellulose derivatives (HPMC, Na CMC, HEC and EC), Carbopol 974P, solubilizer and lubricant were directly compressed into minitablets, using concave 3 mm diameter punches. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, friability, crushing strength, water uptake and in-vitro drug release studies.It was found that the type and amount of cellulose derivatives used, can influence the rate of drug release.The finally selected formulation (B3) contained ethyl cellulose, Carbopol 974P, mannitol, sodium stearyl fumarate and ciprofloxacin, which showed more than 80% drug release over a period of 5h, and complied well in all the physicochemical tests conducted.Based on kinetic studies, formulation B3 was found to best fit the zero order equation. However, the Higuchi and Hixson-Crowell models also showed a good fit. Hence, overall formulation B3 was chosen as the best formulation.

A simple and reproducible HPLC method with spectrophotometric detection was developed for determination of rivastigmine in human plasma. Liquid-liquid extraction of rivastigmine and donepezil (as internal standard) from plasma samples was performed with 1-butanol/n-hexane (2:98 v/v) in alkaline condition followed by back-extraction into diluted acetic acid. Chromatography was carried out using a Silica column (250 mm × 4.6 mm, 5 µm) under isocratic elution with acetonitrile-50 mM aqueous sodium dihydrogen phosphate (17: 83 v/v, pH 3.1. Analyses were run at a flow-rate of 1.3 mL/min at of 50°C. The recovery was 90.8% and 95.7% for rivastigmine and the internal standard donepezil, respectively. The precision of the method was 2.6% to 9.1% over the concentration range of 0.5-16 ng/mL for rivastigmine in plasma with a linearity greater than 0.999. The method was specific and sensitive, with a quantification limit of 0.5 ng/mL and a detection limit of 0.2 ng/mL in plasma. The method was used for a bioequivalence study in healthy subjects.

Voltammetric techniques have been considered as important methods among the analytical techniques used for the identification and determination of trace concentrations of many biological molecules such as L-ascorbic acid (AA). L-ascorbic acid is an electro-active molecule, though it is difficult to determine its value directly with a majority of electrodes made of carbon and transition metals, because of electrode surface problems. The present study is based on I-E curves for AA analysis at various pH. Furthermore, the effects of the presence of other electro-active substances; such as copper, as well as the effect of the sweep rate of potential will be studied.The present study is based on analysis of the current-voltage curves for L-ascorbic acid at varying pH and sweep rate scan values. An analysis was also carried out to measure the influence of the concentration of some electro active species. The peak height of the first oxidation wave is used for L-ascorbic acid assay. L-ascorbic acid was determined in aqueous media by linear-scan voltammetry on a gold electrode; ranging between (1-175 µg/mL). In biologic samples, for elimination of uric acid or some sugars and effects, a significant interference of copper ions whose presence reduces the height of the L-ascorbic acid oxidation peak was used. The optimum pH and sweep rate were 3.2 and 7500mV/s, respectively. Under these conditions, the detection limit of the method was 0.3 µg/mL. Repeatability of the method based on relative standard deviation (RSD) 50, 10 and 1 µg/mL concentrations was 0.83, 2.1 and 10.3%, respectively. The calibration curve was linear over the range 1-175µg/mL (r2 = 0.9977, p < 0.001).The advantage of this method lies in the fact that the use of copper eliminates the interference of different substances such as uric acid.

Lead, cadmium, mercury and arsenic are the most important heavy metals which may cause health risks following consumption of contaminated foods. Table salt is one the mostly used food additive with unique place in food consumption. Although purified table salt is expected to have lower level of contamination, some Iranians still prefer to use rock salt. Use of rock salt for food purposes has been banned by Iranian health authorities. In this study, heavy metal contamination of table salt consumed in Iran has been investigated. One hundred samples of rock and refined table salts were analyzed using atomic absorption spectrophotometeric methods for the presence of toxic heavy metals. The mean concentration of tested tracer metals including Cd, Pb, Hg and As was 0.024, 0.438, 0.021 and 0.094 µg/g, respectively. The concentrations of tested heavy metals were well below the maximum levels set by Codex. However, no statistically significant difference was found between contamination of rock salt and refined salt to heavy metals.

The objective of this study was to investigate the effects of saffron as a natural sunscreen and moisturizer. The pollens of the saffron were dried and powdered in a grinder. The experimental formulations included a homosalate (8%) lotion reference, lotions with 2, 4 and 8% of grinded saffron, and the control lotion base without saffron. The lotions containing saffron were prepared like homosalate lotion reference according to FDA. The sun protection factors (SPFs) of the formulations were determined by an in vitro spectrophotometry method. The moisture contents of the skin before application and after 30 min and 3, 5 and 7 h post-application of the formulations were measured in human volunteers using Corneometer. The results indicated that, there was no significant difference between the SPF values of the 4% saffron lotion and the homosalate lotion reference. However, the SPF of 8% saffron lotion was significantly more than that of homosalate lotion reference. These results showed that in equal concentrations saffron lotion could act as a better antisolar agent compared to homosalate. Furthermore, there were no significant differences in skin moisture saffron lotions and the control lotion without saffron during the 7 h post-application period. Saffron can be used as a natural UV absorbing agent. The 4% saffron lotion showed an SPF value equivalent to the 8% homosalate lotion reference by an in vitro method. There were no significant differences of skin moisture contents after application of the saffron lotions and the control base lotion without saffron.

The genus Phoenix is one of the most widely cultivated groups of palms around the world. The aim of this study was to determine the antioxidant activity and total phenolic compounds of 14 different varieties of date palm (Phoenix dactylifera L., Arecaceae) seed extracts with 5 solvents [water, methanol, methanol (50%), DMSO, and water: methanol: acetone: formic acid (20:40:40:0.1)]. Ferric reducing antioxidant power assay and Folin-Ciocalteu reagent was used for determination of the antioxidant effect and phenolic content of date seeds. DMSO extract of the “Zahedi” variety had the highest antioxidant effect (37.42 mmol/100 g dry plant) and total phenolic content (3541 mg /100 g dry plant) among these 14 varieties and 5 solvents. There was a significant correlation between the total phenolic content and antioxidant activity (R2 = 0.791, P < 0.001) of the “Zahedi” variety DMSO extract, which can indicates that polyphenols are the main antioxidants. Iranian date palm seed has a relatively high antioxidant activity due to contribution of phenolic compounds. The present study showed that the Iranian date seeds are strong radical scavengers and can be considered as a good source of natural antioxidants for medicinal and commercial uses.

Cataract is clouding of the eye lens that reduces the amount of incoming light and results in deteriorating vision. Blindness is thought to reach 75 million by 2020. Of these, unoperated cataract may be expected to account for at least 35 million. Thus, the burden of cataract is increasing remorselessly. Embelica officinalis is reported to have a very good antioxidant property and thus we hypothesized that it could be a good candidate in treatment of cataract. Hence, the aim of this study was to investigate the effect of aqueous extract of Embelica officinalis on selenite induced cataract in rats.For the purpose of this study, cataract was induced in young suckling (on the 10th day of life) albino wistar rats using sodium selenite (a single dose of sodium selenite; 20µM/kg; subcutaneously). After induction of cataract, the test drug (Embelica Officinalis) and the reference standard (ascorbic acid) were administered orally for 18 days. The progression or disappearance of cataract was observed with the help of an ophthalmoscope (OM-18, Takagi resolution 1.6). At the end of this study the alterations in the levels of total protein, soluble protein, reduced glutathione and malondialdehyde were estimated in the lens homogenate.Results showed that treatment with Embelica officinalis, as well as ascorbic acid, produced a significant decrease (p < 0.05) in malondialdehyde and a simultaneous increase in lens glutathione levels (p < 0.05). The malondialdehyde content was decreased by 48% in animals treated with Embelica officinalis. Similarly, lens glutathione was increased by 82.5% in animals treated with Embelica officinalis. There was also a significant (p < 0.05) increase in protein content (total protein = 59.36% and soluble protein = 105.78%) in animals treated with Embelica officinalis, indicating improvement in cataractogenic condition in the selenite induced cataract model. At the end of the treatment, disappearance of cataract was observed in test and standard treated animals. In conclusion, it could be said that aqueous extract of Embelica officinalis delayed the progression of cataract in sodium selenite induced cataractogenic rats.

The present study has been designed to find out the protective effect of aqueus extract of Terminalia arjuna against dehydration induced oxidative stress and uremia، protection by plant extract in male Wister strain albino rats، and therefore to find out the scientific basis of local use of Terminalia arjuna bark extract by village ayurved doctors to protect the progressive kidney disorder (renal failure) relating to dehydration and other related problems. Water withdrawing for 15 days in male Wister strain albino rats resulted in a significant elevation in the level of blood nitrogenous products (i. e. urea and creatinine). On the other hand، it increased the levels of free radicals، melondialdehyde (MDA) and conjugated dienes (CD) along with a significant diminution in the activities of superoxide dismutse (SOD) and catalase in blood. All these water markers were significantly prevented after administration of aqueous extract of Terminalia arjuna bark. These results suggest that dehydration induced oxidative stress and uremia in male rats may be protected by using the above mentioned medicinal plants extract. This herbal extract showed no toxic effect on blood and kidney، based on the measurements of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities (data not shown).

Extracts obtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folk medicine as remedies for the treatment of some inflammatory diseases. In this study the hydroalcoholic extract and essential oil of the plant were investigated for its possible anti-inflammatory and analgesic activities. The extract was administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essential oil were 100, 200 and 400 µL/kg. The acetic acid-induced writhing response, formalin-induced paw licking time in the early and late phases and light tail flick test were used in mice to assess analgesic activity. For evaluation of anti-inflammatory effect carrageenan-induced paw edema served as a valid animal model in rats. The extract significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and also showed potent analgesic effect in both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extract significantly (P < 0.05) reduced carrageenan-induced paw edema. Essential oil of the plant at all administered doses failed to show any analgesic or anti-inflammatory effect in above mentioned tests. These results provide support for the use of hydroalcoholic extract of Rosa damascena in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.

Glucose-6-phosphate dehydrogenase (G6PD) deficient subjects are vulnerable to oxidative stress. Quercetin, a flavonoids, has been employed as a potent oxygen-free radical scavenger in order to assess the protective effects of quercetin against H2O2-induced oxidative damage in G6PD-deficient and normal human erythrocytes. Erythrocytes of G6PD-deficient (n = 10) and normal (n = 10) subjects were incubated with different concentrations of quercetin. The produced thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) level of erythrocytes were then subsequently measured.Different concentrations of quercetin showed no significant hemolysis, compared with the phosphate buffer solution. Upon challenge with H2O2, there was a significant (p < 0.005) decrease in GSH and an increase in TBARS level in G6PD-deficient erythrocytes. With quercetin, it managed to preserve concentrations of 15 to 75 mM preserved GSH and TBARS levels of normal and G6PD-deficient erythrocytes against H2O2-induced oxidative damage.In addition to its well-established antioxidant effects, quercetin was also found to have cytoprotective properties.

Clavulanic acid is produced industrially by fermentation of Streptomyces clavuligerus and researches have increased its production by strain improvement, recombinant DNA technology, and media composition and growth condition optimization. The main objective of this study was to increase the level of clavulanic acid production from Streptomyces clavuligerus (DSM 738), using UV irradiation. After incubation, the spores and aerial mycelia were scraped off the agar plate by a sterile loop. After passing through a cotton wool, the serially diluted spore suspension was spread on GYM- agar containing caffeine. The plates were irradiated with UV light, wrapped in aluminum foil and incubated. The colonies were sub-cultured again to express the mutations. An aliquot of the spore suspension prepared from the resulted culture was poured in GYM agar plates and incubated. The plates were overlaid with nutrient-agar containing penicillin G and Klebsiela pneumoniae, and incubated. The inhibition zone diameter was measured and compared with the wild type colony. Repeating this procedure, the overproducer mutants were selected. Concentration of clavulanic acid was determined by HPLC analysis. It was concluded that secondary metabolites, mainly antibiotics containing clavulanic acid, were produced about 6–7 days after the growth, and concentration of clavulanic acid was increased up to two-folds after UV mutagenesis.

The hippocampal system plays an important role in memory function. Neurohormones like androgens and estrogens that syntheses in hippocampus have an important role in learning and memory. Many biological effects of estrogens in the brain via estrogenic receptors (ERs) are investigated. The current research has conducted to assess the effect of estrogenic receptors on spatial discrimination in rats by using Morris water maze (MWM) task. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and divided in to 9 groups. Different groups received dimethyl sulfoxide (DMSO) 0.5 µl as control groups and different doses of tamoxifen (TAX) as antagonist of ER (0.0625, 0.125 and 0.25µg/0.5µl), propyl pyrazol thiol (PPT) as agonist of ERα (5,10 and 20µg/0.5µl), TAX 0.25µg/0.5µl + PPT 20µg/0.5µl all days 30-35 min before training. Our results have shown TAX (0.25µg/0.5µl), PPT (20µg/0.5µl), TAX (0.25µg/0.5µl) + PPT (20µg/0.5µl) groups significantly increase the escape latency and traveled distance to find invisible platform. Our results indicate that TAX and PPT and also TAX (0.25µg/0.5µl) + PPT (20µg/0.5µl) impaired acquisition of spatial learning and memory. As a consequence, it seems that estrogen modulates memory function via a novel estrogenic mechanism.

Sena-Graph syrup has recently been formulated by an Iranian pharmaceutical company for being used in bowel evacuation before radiography, colonoscopy and surgery. This study compares the efficacy, adverse effects and patient compliance of two bowel preparation regimens with castor oil and Sena-Graph syrup in of outpatients for Intravenous Urography (IVU). One hundred and fourteen consecutive outpatients were randomized to receive either the standard bowel preparation with 60 mL of castor oil or the test method with 60 mL of Sena-Graph syrup before IVU examination. Demographic data of patients and their prior bowel preparation experience were collected before the examination. Two radiologists, blinded to the method of bowel preparation, reviewed the radiographs and graded the bowel preparation. The compliance and acceptability of both regimens were assessed by using structured questionnaires filled by the patients. The Numbers, ages, weights and gender distribution of patients and their prior bowel preparation experience in the two groups did not differ significantly. The cleanliness scores for the castor oil and Sena-Graph group were 3.97 ± 0.971 and 4.87 ± 0.917, respectively. The results indicated that Sena-Graph syrup causes a better bowel cleansing compared castor oil. Adverse effects in Sena-Graph groups were significantly lower than the castor oil group. Acceptability of the regimen in patients who used Sena-Graph was higher than the other group. The Sena-Graph regimen is significantly more effective and better tolerated than of Castor oil regimen in bowel cleansing. The incidence and severity of the adverse effects from Castor oil was higher than Sena-Graph.

Detection of probable harmful consequences arised from the usage of pharmaceutical products requires decisive, continuous and close monitoring by medical staff whom should have knowledge of adverse drug reactions and they should also have to report any suspected instances, when any kind of adverse drug reactions have been observed. This study has been carried out on the knowledge, attitude and practice of nurses towards pharmacovigilance in the Taleqani medical, teaching and treatment center in Tehran, before and after an ADR educational program. This study was commenced in March 2005 and ended in October 2005, using a questionnaire through two steps. In every step, 150 questionnaires were distributed in various wards of the Taleqani Hospital. Collected data were entered into the Excel software and then data analyzed using the SPSS statistical software. Familiarity of nurses with the ADR center and it’s duties is the first step in training how to report ADR, and could help to enhance thire awareness. The use of lecture training for increasing the awareness of nurses was found to be very effective. Regression multivariable analyses showed that the knowledge of nurses, regarding previous familiarity with the ADR center is better than the others (r = 0.38, P = 0.01), and the attitude of female nurses is better than males (r = 0.27, P = 0.01). According to the statistical results, the knowledge of nurses before the seminar was significantly less than the knowledge after the seminar (P= 0.0001), but there was no significant effect on the attitude (P= 0.05). Regarding the submission place of ADR reports, only 3.4% of nurses pointed out to the ADR center. Before and after training, a limited duration of time was reported to be the most restricted factor for clinical recognition of adverse drugs. Based on the results of this study, it is necessary to offer continuous ADR educational program until we reach the point that voluntary reporting of adverse drug reactions becomes conventional and habitual among the nursing staff.