Iranian Journal of Pharmaceutical Sciences
Volume:3 Issue: 2, Spring 2007

The goal of this study was to prepare and characterize alginate microspheres as an antigen delivery system and adjuvant for immunization against leishmaniasis. Microspheres encapsulated with autoclaved Leishmania major (ALM) and Quillaja saponin (QS) were prepared by an emulsification technique and characterized for size, encapsulation efficiency and release profile of encapsulates. Selection of appropriate parameters (viscosity of alginate, emulsifier and sonication times) enabled the preparation of alginate microspheres with a mean diameter of 1.92±1.0 μm, as determined by scanning electron microscopy and particle size analyzer. The encapsulation efficiency was about 34.2±6.7% for ALM and 31.0±4.4% for QS, as determined by spectrophotometric assays. In vitro release profile showed a slow release rate for encapsulated ALM and QS, 35.7±8.7% of ALM and 36.9±4.7% of QS were released during 1 week. The molecular weight was evaluated by SDS-PAGE and showed that the process of encapsulation did not affect the molecular weight of the entrapped antigen. With regard to the optimum diameter (less than 5 m), slow release rate and preservation of antigen molecules, formulated alginate microspheres could be considered as a promising antigen delivery system and adjuvant for ALM and QS.

Ibuprofen solid dispersions were prepared by the solvent and fusion-solvent methods using polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), eudragit RS PO, eudragit RL PO and hydroxypropylmethylcellulose (HPMC) as carriers to improve physicochemical characteristics of ibuprofen. The prepared solid dispersions were evaluated for the flowability, solubility characteristics and dissolution behavior. Flowability studies of powders showed that solid dispersion technique improve flow properties compared with the physical mixtures. Solid dispersion technique found to be effective in increasing the aqueous solubility of ibuprofen. The dissolution of ibuprofen and polymers (PVP, HPMC, eudruagit and PEG-6000) were investigated using UV spectroscopy. Dissolution was carried out in phosphate buffer (pH 6.8) using a standard USP II dissolution apparatus. In vitro dissolution studies showed that in the dispersion systems containing eudragit or HPMC, dissolution of ibuprofen was retarded, which attributed to ionic interaction and gel forming, respectively. But solid dispersion containing PEG, as a carrier, gave faster dissolution rates than the physical mixtures. Finally, solid dispersion of ibuprofen:PEG 6000 prepared in 1:1.5 ratio showed excellent physicochemical characteristics and was found to be described by the zero order kinetic, and was selected as the best formulation in this study.

Throughout the world, there has been an increasing incidence of fungal infections, and because of drug resistance and toxicity associated with long-term treatment with antifungal drugs search for new drugs to treat fungal infections is ongoing. The aim of this study was to evaluate the physicochemical properties and stability of creams containing different concentrations of Zataria multiflora extract as anti-dermatophyte preparations. First, the minimum inhibitory concentration (MIC) of methanolic extract of aerial parts of Z. multiflora was assayed against various dermatophytes by in vitro tube dilution technique (MIC=0.5%). To select the best cream formulation, one general formula of cleansing cream was considered and then corrected. The best base formula was chosen according to its monotonousness, straightness and external attractiveness. Formulations containing 1, 2 or 3% of the plant extracts were prepared. Finally, a cream containing 10% bees wax, 58.8% liquid paraffin, 1.2% hard paraffin, 5% spermaceti, 1% borax, 1.4% tween 80, 0.15% methyl paraben, 0.15% lactic acid, 0.05% propyl paraben, 2% Zataria extract and water was chosen as the best formulation. The final product was a W/O cream with suitable appearance and desirable physicochemical stability.

Acidic pH of stomach, which is a normal physiological barrier against bacterial overgrowth, would increase by stress ulcer prophylaxis initiation and may lead to bacterial colonization and play as a source for infection transmission to the respiratory system which results in ventilator related pneumonia in patients admitted to the Intensive Care Units (ICUs). Therefore, finding methods to decrease the prevalence of aspiration pneumonia is an old debate. The current survey has been performed to evaluate the effect of ranitidine and sucralfate on bacterial colonization and development of aspiration pneumonia. This is a randomized clinical trial in two groups of fifteen critically ill patients older than 20 years of age admitted to the ICU of Sina Hospital, Tehran, Iran. All patients were under mechanical ventilation. One group had a regimen of 1 g sucralfate every 6 h by gavage and the other had 50 mg of intravenous ranitidine every 8 h with a loading dose of 100 mg. Gastric juice was sampled every 24 h for determining the pH and pathogen type. The gastric pH of ranitidine group was higher than of sucralfate group. Common microorganisms colonized in the gastric juice of patients were Pseudomonas, Staphylococcus aureus, Klebsiella, and Candida albicans. Aspiration pneumonia occured in 4 patients in the ranitidine group and 2 patients in the sucralfate group. Similar frequency of colonized microorganisms in the two groups suggests that the effect of pH on bacterial colonization is negligible. Therefore, concurrent consumption of ranitidine and other acid lowering medications may lower the risk of aspiration pneumonia and stress ulcer in patients taking ranitidine. If it is the case, administration of ranitidine would be preferred to sucralfate.

Callus and suspension cultures of Lavandula angustifolia Mill. (Lamiaceae) were established and the effect of different culture media on growth rate was investigated. Terpenoids added to suspension culture to investigate their biotrans-formation. All samples were analyzed by gas chromatography (GC) and GC-mass spectroscopy (MS). Octan-1-ol, citronellol, linalool, borneol and geraniol were biotransformed products of octanal, citronellal, linalyl acetate, bornyl acetate and geranyl acetate, respectively. Citronellol, linalool, borneol, and menthol didn't change by L. angustifolia suspension cultures. Blue pigment production by cultures of L. angustifolia was also studied. Ester hydrolysis and oxidation were the main reactions which occurred in biotransformation process, which may be attributed to the presence of related or bifunctional enzymes. This technique is a possible way of the production of expensive or rare compounds from cheap and plentiful substrates.

In this study a new simple selective and sensitive spectrophotometric procedure for determination of Fe(III) is described. It is based on the formation of a colored complex between ferric iron and ethyl maltol, a strong and highly selective ligand for Fe(III). After mixing sample and reagent, and incubating at the room temperature, Fe(III)-ethyl maltol complex was extracted with different solvents and the absorbance was measured at 395 nm. The effect of analytical variables, i.e. amount and type of the reagents, pH, ratio of Fe(III)/ethyl maltol, presence of other ions, etc., in the determination of iron were studied. Our findings showed that the optimum wavelength for the measurement was 395 nm. The optimum condition for complex formation and determination of Fe(III) were: molar ratio of ethyl maltol/Fe(III) = 6-10; pH = 5. The best solvent for extraction was chloroform. Under the recommended conditions, formation of the complex is completed in less than 2.5 h. Limit of detection was found to be 2.5×10-6 M of Fe(III). Linear regression (r2=0.9998) was observed over the range of 2.5×10-6 to 5×10-4 M of the Fe(III) with respect to the complex nominal concentration. Ions commonly associated with iron did not interfere in the present method. This is a simple, reproducible, and sensitive method for determination of Fe(III) in μmolar levels.

A simple, rapid, selective and highly sensitive fluorimetric method for determination of two catecholamines, i.e. norepinephrine (NE) and epinephrine (EP), in serum samples was developed. The method is based on the fluorescence sensitization of terbium (Tb3+) by complexation with both catecholamines in the presence of lanthanum (La3+), as a co-cation, and in a Na2SO3 solution (chemical deoxygenating agent), which fluoresces intensely with an emission maximum at 545 nm when excited at 312 nm. We found that fluorescence enhancement effects were observed when La3+ was added to the system (co-luminescence effect). In the presence of this element the fluorescence of the Tb-catecholamines system was enhanced by a factor of about 15 compared with that of the system without La3+. Optimum conditions for the formation of the complexes were investigated. Under optimum conditions, a linear relationship was obtained between the fluorescence intensity and catecholamines concentration in the range of 2.5×10-3 to 0.22 μg.ml-1. The detection limits were 0.59 and 0.58 μg.l -1 for EP and NE, respectively. Relative standard deviation (RSD) values for two compounds were in the range of 1.2-2.1% indicating excellent reproducibility. The proposed method was successfully applied to the determination of EP and NE in spiked serum samples after deproteiniza-tion of the samples with acetonitrile. Analytical recoveries from treated serum samples were in the range of 95-105%.

Drug design is generally achieved through trial and error methods, which is a time and resource consuming process and novel methods are needed to improve it. Mathematical modelling is one of the possible solutions to speed up this process. In this study, we have presented Box-Jenkins model, to predict the vasorelaxant activity (pEC50) of a set of benzopyrane compounds. We used the HyperChem software to extract the molecular features of these compounds (51 molecules); then these features were used to generate the Box-Jenkins model. The dataset was divided into three groups: 37 for training, 9 for prediction and 5 for validation. The absolute relative deviation of the predicted values was 4.8% and 4.1% for validation and predicton sets, respectively. The correlation coefficient between the predicted points and the experimental values was 0.9657, revealing that the proposed model is capable of representing pEC50 of benzopyranes and could be used to speed up drug discovery processes.