Iranian Journal of Pharmaceutical Sciences

Onopordon known as scotch thistle is a medicinal plant of the Asteraceae family that is widely distributed in Europe and Asia, also it has many valuable medicinal properties as hypotensive and antitumor. Thin layer chromatography (TLC) is wildly used in natural product extract analysis as a finger print which can be used for identification and quality control of medicinal preparations. Performing Thin-layer chromatography TLC tests on the plant shows the presence of flavonoids, coumarins, and bitter principles. Planar chromatographic analysis hyphenated with the biological detection method is known as bioautography which is an effective and inexpensive technique for the phytochemical analysis of plant extracts. Thin-layer chromatography-direct bioautography links separation on the adsorbent layer with biological tests performed directly on it in order to identify antimicrobial and antioxidant activities. Bioautography revealed that Staphylococcus aureus was inhibited by most of the flavonoids separated on the TLC plates. Similarly, growth of the Bacillus cereus was also inhibited by one flavonoid band on TLC. Antioxidant bioautography shows the strong antioxidant activity of one flavonoid band, whereas no activity detected of bitter principles. Bioautography showed that the antimicrobial and antioxidant activity was probably due to flavonoids.

The aim of the present study was to develop and investigate the feasibility of delivering Nebivolol as a transdermal patch by iontophoresis. The passive and electrically assisted transdermal delivery of Nebivolol hydrochloride by iontophoresis will improve the therapeutic efficacy and overcome the difficulties raised in oral drug delivery. Because of its extensive hepatic metabolism and low dose, Nebivolol hydrochloride become a suitable candidate for transdermal administration. The matrix transdermal patches of Nebivolol hydrochloride were prepared and tested for in-vitro drug release and ex-vivo permeation. The study was conducted with the help of silver-silver chloride electrodes by iontophoresis across hairless rat skin. Drug release was evaluated in the presence of iontophoresis field using a current density of 0.5 mA/cm2 or without electric field i.e passive diffusion by the process of electro-migration and electro-osmosis. Drug was measured spectrophotometrically and flux was determined. The flux of Nebivolol significantly increased (P<0.05) with increase in current strength from 0.5 – 1.0 mA/cm2. The findings show that Nebivolol hydrochloride matrix transdermal therapeutic systems could be prepared with the required flux having suitable mechanical properties. It can be concluded from the results that the appliance of iontophoresis with penetration enhancer enhances the flux compared to the passive diffusion.

Apigenin is best known as an irreversible inhibitor of monoamine oxidase (MAO), an intracellular enzyme associated with the outer membrane of mitochondria. The purpose of this study is to establish a reliable and quick method for the assignment of apigenin in Cosmos bipinnatus, Apium graveolens, and Petroselinum crispum by HPLC. A rapid and sensitive HPLC method has been developed for determination of apigenin. Mobile phase was composed water-acetonitrile (55:45 v/v) with a flow rate of 1 ml/min and the eluted peaks were detected by a UV detector set at wavelength of 340 nm. The method was validated in the range of apigenin concentrations from 0.01 to 500 μg/ml and the limits of detection (LOD) and quantitation (LOQ) of the method were 0.005 and 0.01 μg/ml, respectively. The average recovery throughout the linear concentration range was 97.28 percent and the averages for within-run and between-run accuracy values were 99.32 and 96.79 respectively. The method is quick, simple, sensitive, and precise for the screen, assignment, and evaluation of apigenin in plants by HPLC.

L-Asparaginase has remarkable properties which make it useful in dual pharmaceutical and food industries.In this study, simple and advantageous methods have been validated for rapid and precise
determination of intracellular L-Asparaginasein bacterial species. A suspension of bacterial cells was used instead of cell extract and incubated by substrate (asparagine) after simple wash and centrifugation steps. Due to loss of enzyme activity which could be caused by cell distruption methods such as sonication or enzymatic treatment, cell suspension was used instead of the cell extract. Thus, this method not only is cost effective but also speeds up the screening process and leasd to higher measurement accuracy. To validate this method, two species of bacteria; E.coli ATCC 8739 and Halomonas H28 were used. After cultivation, the cells were harvested and washed. Then, 5 serial dilutions were prepared from each bacterium, and the asparaginase activity in each of them was measured by methods including sonication, enzymatic lyses, and the cell suspension. The results have showed that the changes in asparaginase activity in all 5 serial dilutions are linear and there is good agreement between the sonication and the cell suspension methods. Also, it was shown that activities measured by the enzymatic method were significantly higher than the other two methods.

In this paper a fast and novel stability-indicating ultra fast LC method for separation and estimation of impurities in clopidogrel and aspirin in their combined tablet dosage form and omeprazole was developed. The separation of USP related substances of clopidogrel (A, B and C), aspirin (D), omeprazole (A, B and C) and few other unknown impurities was detected by using ultra fast liquid chromatography with PDA detection. The maximum detection was set as follows: 237 nm for aspirin, its impurities and for the impurity C of Clopidogrel and 254 nm for Clopidogrel and its impurities except for impurity C and 280 nm for omeprazole and its impurities. Phenomenex C8 (250 mm × 4.6 mm, 5μ) was used as a stationary column to separate and analyze the mixture within 11 min with a programmed gradient elution of 0.01 M phosphate buffer pH 2.0 and acetonitrile. The method was successfully validated in accordance to the International Conference of Harmonization (ICH) guidelines for clopidogrel and its impurities, aspirin and its impurity D and omeprazole and its impurities A, B and C. The tablets were exposed to acid, alkaline, thermal, higher humidity, oxidative and photolytic stress conditions. Samples undergone stressed conditions were analyzed by the novel proposed method. Separation was satisfactory for all the significant degradation products from the principal peaks of drug substances and the impurities from each other. The method complies for the peak purity test for clopidogrel, aspirin and omeprazole in all the samples under stress and showed no co-elution of degradation products. The method was found to be stable, precise, linear, accurate, sensitive, specific and robust. The method can be used routinely to test the adulteration in the pharmaceutical formulations of clopidogrel, aspirin, and omeprazole.

The main objective of the present research work is to formulate the Clopidogrel Fast Dissolving tablets. Clopidogrel, an antiplatelet drug, belongs to BCS Class-II and used to control Heart attack, Hypertension by inhibiting Platelet activation and aggregation .The Fast Dissolving tablets of Clopidogrel were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrant by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50%, t90% were selected as dependent variables. Totally nine formulations were designed and evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, and in-vitro drug release. From the Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the in-vitro dissolution profiles of all formulations were fitted into different Kinetic models, the statistical parameters like intercept (a), slope (b) and regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations was verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines, the formulation (F5) containing combination of 15% Crospovidone and 15% Croscarmellose, is the most similar formulation (similarity factor f2=91.3936, dissimilarity factor f1= 1.203& No significant difference, t= -0.00062) to marketed product (PLAVIX-75). The selected formulation (F1) follows First order, Higuchi’s kinetics, mechanism of drug release found to be Fickian Diffusion (n= 0.226).

Perfluorooctanesulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxin effects. Due to chemical properties, PFOS shows persistency in the environment and therefore has potential hazardous effect. The risk of possible intra uterine exposure to PFOS poses a health concern for developmental effects. The goal of this study was survey of histological and behavioral changes made by PFOS in pregnant mice and their fetuses using common behavioral assays and H&E staining. In the present study, doses of PFOS (1, 10, 20 mg/kg) were given orally to pregnant mouse from gestational day (GD) 0 to GD14; then on the day 15, Behavioral experiments including (open field and passive avoidance) were used to assess toxic behavioral changes such as memory impairment and anxiety. After behavioral evaluations, fetuses were dissected on day 15 of gestation and morphological and histological studies on pregnant mouse brain and her fetus were carried out using haematoxylin-eosin staining method. Our findings showed that PFOS could induce neurotoxicity in pregnant mouse especially by induction of abnormalities in dentate gyrus of hippocamps and disruption of neurobehavioral functions .Besides in her fetus; PFOS produced significant changes in brain, liver, and thyroid gland in comparison with untreated control mouse fetus. As a conclusion, PFOS can cause both neurobehavioral and developmental toxicity in pregnant mouse and her fetus.

Bypassing agents are the most commonly used medicines for the treatment of hemophilia patients with inhibitors. The aim of this study is to identify the cost components of management of bleeding vents in hemophilia patients with inhibitors in Iran.This study is a cross-sectional study using a bottom-up approach to determine the cost components of treatment of hemophilia patients with inhibitors via ascertaining of all direct medical and non-medical costs.The evaluatiion of cost components of 20 patients with 40 episodes of bleeding showed that the price of medicines used is responsible for more than 96% and 97% of costs in treatment of hemophilia patients using FEIBA® and AryoSeven, respectively. The results of this study showed that cost of treating one bleeding episode in hemophilia A patients with high antibody titer using FEIBA is 376 USD compared to 857.3 USD for AryoSeven®.Despite the small number of hemophilia patients with inhibitor in Iran, due to high cost of treating these patients, it is very important to choose the cost-effective treatment protocol for the treatment of these patients.