Advanced Pharmaceutical Bulletin
Volume:4 Issue: 2, Jun 2014

Nearly all of flavonoids are good metal chelators and can chelate many metal ions to form different complexes. This article describes a synthesis of Quercetin–Tb(III) in methanol, characterized by using elemental analysis, UV–visible and evaluation of its antioxidant properties. The formation of complexes is realized from the UV–visible spectra which shows that the successive formation of Quercetin–Tb(III) occurs. To find out the antioxidant activity variation and the role of Tb(III) ion on the antioxidant activity of the complexes different radical scavenging methods such as: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2′-azinobis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) were used. The results from DPPH, ABTS and FRAP methods showed that Quercetin and Quercetin–Tb(III) complex are capable of donating electron or hydrogen atom, and consequently could react with free radicals or terminate chain reactions in a time- and dose-dependent manner. This study showed that the chelation of metal ions by Quercetin decrease the redox potential of Quercetin-metal complex.

An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl)-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. The desired compounds (S1-S10) were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 μg/ml and compound S6 was exhibited antifungal potential at 15.62 μg/mL on both fungal strains. Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics.

Recently the liquid nanoemulsifying drug delivery systems (SNEDDS) have shown dramatic effects on improving oral bioavailability of poorly soluble drugs. The main purpose of this study was to prepare a solid form of self-nanoemulsifying drug delivery system of loratadin by extrusion-spheronization. The liquid SNEDDS are generally prepared in a soft or hard gelatin capsules which suffers from several disadvantages. Therefore incorporation of SNEDDS into solid dosage form is desirable to get together the advantages of SNEDDS and solid multiparticualte systems. The SNEDDS was consisted of liquid paraffin, capriole, span 20, transcutol and loratadin as a poorly soluble drug. A multilevel factorial design was used to formulation of SNEDDS pellets, liquid SNEDDS (20 and 30%) was mixed with lactose, microcrystallin cellulose (40%) and silicon dioxide (0, 5 and 10%), and Na- crosscarmelose (0, 5 and 10%). The resulting wet mass transformed into pellets by extrusion-spheronization. The pellets were dried and characterized for size (sieve analysis), shape (image analysis), mechanical strength (friability test), droplet size (laser light scattering) and drug release rate (dissolution test). Selected SNEDDS pellets were also compared with conventional loratadin pellet or tablet formulation. The resulting SNE pellets exhibited uniform size and shape. Total friability of pellets did not affected by formulation variables. The in vitro release of SNE pellets was higher than the liquid SNE and powder tablets. Our studies demonstrated that extrusion-spheronization is a viable technology to produce self-emulsifying pellets in large scale which can improve in vitro dissolution with better solubility.

The objective of this work was to develop a bioadhesive topical gel of sertaconazole nitrate with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Carbapol 934 = X1) and Sodium carboxymethylcellulose (NaCMC) = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial design and generated quadratic mathematical equations. On the basis of product characteristics viscosity, bioadhesiveness, permeation study, in-vitro release, in-vivo studies, TPA and spreadability it can be concluded that the best batch of topical bioadhesive gel of Sertaconazole nitrate would be with 1% Carbopol 934 and 1% NaCMC.

Nowadays adenosine is specified as an important factor in the pathophysiology of asthma. For determining the effect of different A2 receptors, in this investigation the effect of single dose of selective adenosine A2A and A2B antagonists (ZM241385 and MRS1706) on different inflammatory parameters; tracheal responsiveness to methacholine and ovalbumin, total and differential cell count in bronchoalveolar lavage (BAL), blood levels of IL-4 and IFN- and lung pathology of guinea pig model of asthma were assessed. All mentioned parameters were evaluated in two sensitized groups of guinea pigs pretreated with A2A and A2B antagonists (S+Anta A2A, S+Anta A2B) compared with sensitized (S) and control (C) groups. The tracheal responsiveness to methacholine and OA, total cell and eosinophil and basophil count in BAL, blood IL-4 level and pathological changes in pre-treated group with MRS1706 (S+Anta A2B) was significantly lower than those of sensitized group (p<0.01 to p<0.05). In pretreated group with Anta A2A(S+Anta A2A), all the above changes were reversed. These results showed a preventive effect of A2B antagonist (MRS1706) on tracheal responsiveness to methacholine and OA, total and differential cell count in bronchoalveolar lavage, blood cytokines and pathological changes. Administration of ZM241385, selective A2A antagonist, deteriorated the induction effect of ovalbumin.

This study was aimed to design Objective Structured Field Examination (OSFE) and also standardize the course plan of community pharmacy clerkship at Pharmacy Faculty of Tabriz University of Medical Sciences (Iran). The study was composed of several stages including; evaluation of the old program, standardization and implementation of the new course plan, design and implementation of OSFE, and finally results evaluation. Lack of a fair final assessment protocol and proper organized educating system in various fields of community pharmacy clerkship skills were assigned as the main weaknesses of the old program. Educational priorities were determined and student’s feedback was assessed to design the new curriculum consisting of sessions to fulfill a 60-hour training course. More than 70% of the students were satisfied and successfulness and efficiency of the new clerkship program was significantly greater than the old program (P<0.05). In addition, they believed that OSFE was a suitable testing method. The defined course plan was successfully improved different skills of the students and OSFE was concluded as a proper performance based assessment method. This is easily adoptable by pharmacy faculties to improve the educational outcomes of the clerkship course.

The aim of this study was to evaluate antioxidant ability of mangosteen shell and explore the non-enzymatic repair reaction and possible mechanism of xanthones in mangosteen shell. Mangosteen shell was extracted by methanol to obtain the extract of mangosteen shell. The extract was then determined by various antioxidant assays in vitro, including protection against DNA damage, •OH scavenging,DPPH• (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS+• (2,2′-azino-bis(3-ethylbenzo- thiazoline-6-sulfonic acid diammonium) scavenging, Cu2+-chelating, Fe2+-chelating and Fe3+ reducing assays. Mangosteen shell extract increased dose-dependently its percentages in all assays. Its IC50 values were calculated as 727.85±2.21,176.94±19.25, 453.91±6.47, 84.60±2.47, 6.81±0.28, 1.55±0.10, 3.93±0.17, and 9.52±0.53μg/mL, respectively for DNA damage assay, •OH scavenging assay, Fe2+-Chelating assay, Cu2+-Chelating assay, DPPH• scavenging assay, ABTS+• scavenging assay, Fe3+ reducing assay and Cu2+ reducing assay. On the mechanistic analysis, it can be concluded that mangosteen shell can effectively protect against hydroxyl-induced DNA oxidative damage. The protective effect can be attributed to the xanthones. One approach for xanthones to protect against hydroxyl-induced DNA oxidative damage may be ROS scavenging. ROS scavenging may be mediated via metal-chelating, and direct radical-scavenging which is through donating hydrogen atom (H·) and electron (e). However, both donating hydrogen atom (H·) and electron (e) can result in the oxidation of xanthone to stable quinone form.

Oxidative stress and renin- angiotensin system are both involved in the pathophysiology of most of the systemic and central disorders as well as in aging. Angiotensin converting enzyme (ACE) inhibitors, well known for their cardiovascular beneficial effects, have also shown antioxidant properties in pathologic conditions. This study aimed to evaluate the central effect of ACE inhibitors on oxidative status under no pathologic condition. Adult male rats were divided into four groups of 9 rats each. Groups were treated orally by perindopril at the doses of 1, 2, 4 mg/kg/day or normal saline as the control for four consecutive weeks. At the end of the treatment period the reduced and oxidized glutathione (GSH and GSSG respectively) and malondialdehyde (MDA), the product of lipid peroxidation, were measured in the rats’ hippocampus. The GSH increased dose dependently and was significantly higher in the 2 mg/kg perindopril treated group than the control group (p<0.05) while the GSSG level remained unchanged. As a consequent, the ratio of GSH to GSSG increased significantly in a dose dependent manner. There was not any significant change in MDA. This study demonstrated that ACE inhibition may cause an increase in GSH as an anti- oxidant defense in the hippocampus.

The aim of the study was the development of a simple and rapid analytical procedure for the determination of the most frequently used antihistamine derivatives. A capillary zone electrophoretic method was developed for the simultaneous separation of loratadine, desloratadine and cetirizine. Efforts were focused primarly on the optimisation of the experimental parameters: buffer composition and concentration, buffer pH, applied voltage, temperature, injection pressure and time. The optimised parameters for the separation were: 25 mM buffer electrolyte, buffer pH 2.5, voltage + 25 kV, temperature 25 °C, injection pressure 50 mbar, injection time 3 seconds, capillary 48 cm (effective length 40 cm) x 50 m, detection at 240 nm. Under these conditions, the analysis time was below 5 minutes, the order of migration being: desloratadine, cetirizine and loratadine. The developed method was validated in terms of linearity, limits of detection and quantification, intra- and inter-day precision, selectivity and robustness. Capillary zone electrophoresis proved to be a suitable method for the simulatneous determination of the three studied antihistamine derivatives.

The purpose of this research was to established new polysaccharide for the colon targeted drug delivery system, its formulation and in vitro and in vivo evaluation. Microspheres containing pectin and bora rice were prepared by ionotropic gelation technique using zinc acetate as cross linking agent and model drug used was glipizide. A 32 full factorial design was employed to study the effect of independent variables, polymer to drug ratio (A), and concentration of cross linking agent (B) on dependent variables, particle size, swelling index, drug entrapment efficiency and percentage drug release. Results of trial batches indicated that polymer to drug ratio and concentration of cross linking agent affects characteristics of beads. Beads were discrete, spherical and free flowing. Beads exhibited small particle size and showed higher percentage of drug entrapment efficiency. The optimized batch P2 exhibited satisfactory drug entrapment efficiency 68% and drug release was also controlled for more than 24 hours. The polymer to drug ratio had a more significant effect on the dependent variables. In vivo gamma scintigraphy study of optimized pectin-bora rice beads demonstrated degradation of beads whenever they reached to the colon. Bora rice is potential polysaccharide for colon targeted drug delivery system.

The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N`-diphenyl, N-phenyl-N`-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-yl)thio substituents on the formalin-evoked pain in mice. Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomethacin(20 mg/kg) and vehicle of the compounds. Area under the pain score curve against time (AUEC) up to 60 minutes was used as the measure of pain behavior. A rather good analgesic effect was seen for most of the tested biuret derivatives. Significant reduction in median AUEC0-5 minutes was observed at the doses of 50 and 25 mg/kg for biurets with either benzyl and 2-methylquinoline-4-yl (C8) or phenylethyl and benzo[d]thiazol-2-ylthio(C9) moieties, respectively(p-value<0.0044). Antinociceptive activities of compound C7 (with bis phenylropyl substituent), C8 and C9 during the late phase of formaldehyde-induced pain were comparable to that of indomethacin. Unlike indomethacin, the tested biuret compounds are able to induce antinociception in both phases of formalin test and could be considered comparable to indomethacin at the selected doses.

Intensive chemotherapy with daunorubicin (DNR) is associated with serious side effects in acute myeloid leukemia (AML) patients. In this study the effect of small-molecule BH3-mimetic, ABT-737, on the sensitivity of HL60 and U937 AML cell lines was investigated. The cytotoxic effects of DNR and ABT-737, alone or in combination were assessed using MTT assay and combination index analysis. The effects of treatments on the cell proliferation was determined by trypan blue assay. ELISA cell death assay was used for measurement of apoptosis. IC50 values of DNR and ABT-737 were 2.52 and 0.59 μM for HL-60 cells line and 1.31 and 0.80 μM for U937 cell line at 24 h, respectively. Surprisingly, combination treatment significantly lowered the IC50 values in a synergic manner in both cell lines. Moreover, treatment with a mixture of two agents had more growth inhibition effect relative to the monotherapy. Results of apoptosis assay showed that the cytotoxic effects are related to the enhancement of apoptosis. Our study suggests that ABT-737 synergistically enhances the cytotoxic effect of DNR in AML cell lines and therefore may be useful to overcome chemoresistance of leukemia patients.

The present study was explored to develop a sustained release matrix tablet of Indapamide, a low-dose thiazide-type diuretic, using hydroxylpropyl methylcellulose (Methocel K15MCR) in various proportions as release controlling factor.

The tablets were formulated using direct compression method. The powers for tableting were evaluated for angle of response, loose bulk density, tapped bulk density, compressibility index, total porosity and drug content etc. The tablets were subjected to thickness, weight variation test, drug content, hardness, friability, and in vitro dissolution studies.

The granules showed satisfactory flow properties, compressibility index, and drug content. All the formulated tablets complies pharmacopoeia specifications. The release kinetics of the drug decreased exponentially with the addition of polymer concentration. Indapamide release rate was observed to be the highest with the lowest concentration of polymer used. The release mechanism was explored with zero order, first order, Higuchi and Krosmeyer equations. Stability tests of the drug showed no notable changes in the rate of drug release, related substances and drug content.

In the context, it can be suggested that this formulation of sustained release Indapamide tablets can be marketed to treat patients with hypertension ensuring proper healthcare.

Rosuvastatin is a poorly water soluble drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Hence it is necessary to increase the solubility of the Rosuvastatin. Several liquisolid tablets formulations containing various drug concentrations in liquid medication (ranging from 15% to 25% w/w) were prepared. The ratio of Avicel PH 102 (carrier) to Aerosil 200 (coating powder material) was kept 10, 20, 30. The prepared liquisolid systems were evaluated for their flow properties and possible drug-excipient interactions by Infrared spectra (IR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD). The liquisolid system showed acceptable flow properties. The IR and DSC studies demonstrated that there is no significant interaction between the drug and excipients. The XRPD analysis confirmed formation of a solid solution inside the compact matrix. The tabletting properties of the liquisolid compacts were within the acceptable limits. Liquisolid compacts demonstrated significantly higher drug release rates than those of conventional and marketed tablet due to increasing wetting properties and surface area of the drug. This study shows that liquisolid technique is a promising alternative for improvement of the dissolution rate of water insoluble drug.

Nanoprecipitation is the convenient and commonly used method for the preparation of polymeric nanoparticles around 170 nm but yield particles with broad distribution, which require filtration step to produce particles with narrow distribution. Hence, the primary aim of the present study was to implement few modifications to the conventional nanoprecipitation method to reduce the mean particle size less than 150 nm and to produce particles with narrow distribution without filtration step. Eudragit E 100 nanoparticles were prepared using modified nanoprecipitation method 1 and 2. Prepared nanoparticles were characterized for the mean particle size, surface area and uniformity. Eudragit E 100 nanoparticles prepared using modified nanoprecipitation method 1 has shown a mean particle size of 196 nm with surface area of 50.9 m2g-1 and uniformity of 0.852 whereas, Eudragit E 100 nanoparticles prepared using modified nanoprecipitation method 2 has shown a mean particle size of 114 nm with surface area of 57.9 m2g-1 and uniformity of 0.259. Modification to the conventional nanoprecipitation method (method 2) has produced mean particle size less than 150 nm and produced nanoparticles with narrow distribution without filtration step.