Iranian Journal of Pharmaceutical Sciences

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

Ibuprofen solid dispersions were prepared by the solvent and fusion-solventmethods using polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), eudragit RSPO, eudragit RLPO and hydroxypropylmethylcellulose (HPMC) as carriers toimprove physicochemical characteristics of ibuprofen. The prepared solid dispersionswere evaluated for the flowability, solubility characteristics and dissolution behavior.Flowability studies of powders showed that solid dispersion technique improve flowproperties compared with the physical mixtures. Solid dispersion technique foundto be effective in increasing the aqueous solubility of ibuprofen. The dissolution ofibuprofen and polymers (PVP, HPMC, eudruagit and PEG-6000) were investigatedusing UVspectroscopy. Dissolution was carried out in phosphate buffer (pH 6.8)using a standard USPII dissolution apparatus. In vitrodissolution studies showedthat in the dispersion systems containing eudragit or HPMC, dissolution of ibuprofenwas retarded, which attributed to ionic interaction and gel forming, respectively. Butsolid dispersion containing PEG, as a carrier, gave faster dissolution rates than thephysical mixtures. Finally, solid dispersion of ibuprofen:PEG 6000 prepared in 1:1.5ratio showed excellent physicochemical characteristics and was found to be describedby 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 withantifungal drugs search for new drugs to treat fungal infections is ongoing. The aimof this study was to evaluate the physicochemical properties and stability of creamscontaining different concentrations of Zataria multifloraextract as anti-dermatophytepreparations. First, the minimum inhibitory concentration (MIC) of methanolic extractof aerial parts of Z. multiflora was assayed against various dermatophytes by in vitrotube dilution technique (MIC=0.5%). To select the best cream formulation, onegeneral formula of cleansing cream was considered and then corrected. The best baseformula was chosen according to its monotonousness, straightness and externalattractiveness. Formulations containing 1, 2 or 3% of the plant extracts wereprepared. 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%Zatariaextract and water was chosenas the best formulation. The final product was a W/O cream with suitable appearanceand 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 occurred 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 angustifoliaMill. (Lamiaceae)were established and the effect of different culture media on growth rate wasinvestigated. Terpenoids added to suspension culture to investigate their biotrans-formation. All samples were analyzed by gas chromatography (GC) and GC-massspectroscopy (MS). Octan-1-ol, citronellol, linalool, borneol and geraniol werebiotransformed products of octanal, citronellal, linalyl acetate, bornyl acetate andgeranyl acetate, respectively. Citronellol, linalool, borneol, and menthol didn'tchange by L. angustifoliasuspension cultures. Blue pigment production by culturesof L. angustifoliawas also studied. Ester hydrolysis and oxidation were the main reactions which occurred in biotransformation process, which may be attributed tothe presence of related or bifunctional enzymes. This technique is a possible wayof the production of expensive or rare compounds from cheap and plentiful substrates.

In this study a new simple selective and sensitive spectrophotometric procedurefor determination of Fe(III) is described. It is based on the formation of a coloredcomplex between ferric iron and ethyl maltol, a strong and highly selective ligandfor 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 absorbancewas measured at 395 nm. The effect of analytical variables, i.e. amount and typeof the reagents, pH, ratio of Fe(III)/ethyl maltol, presence of other ions, etc., in thedetermination of iron were studied. Our findings showed that the optimum wavelengthfor the measurement was 395 nm. The optimum condition for complex formationand 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 recommendedconditions, formation of the complex is completed in less than 2.5 h. Limit of detectionwas found to be 2.5×10-6M of Fe(III). Linear regression (r2=0.9998) was observedover the range of 2.5×10-6to 5×10-4M of the Fe(III) with respect to the complexnominal concentration. Ions commonly associated with iron did not interfere in thepresent method. This is a simple, reproducible, and sensitive method for determinationof Fe(III) in μmolar levels.

Asimple, rapid, selective and highly sensitive fluorimetric method fordetermination of two catecholamines, i.e. norepinephrine (NE) and epinephrine (EP),in serum samples was developed. The method is based on the fluorescencesensitization of terbium (Tb3+) by complexation with both catecholamines in thepresence of lanthanum (La3+), as a co-cation, and in a Na2SO3solution (chemicaldeoxygenating agent), which fluoresces intensely with an emission maximum at 545nm when excited at 312 nm. We found that fluorescence enhancement effects wereobserved when La3+was added to the system (co-luminescence effect). In thepresence of this element the fluorescence of the Tb-catecholamines system wasenhanced by a factor of about 15 compared with that of the system without La3+.Optimum conditions for the formation of the complexes were investigated. Underoptimum conditions, a linear relationship was obtained between the fluorescenceintensity and catecholamines concentration in the range of 2.5×10-3to 0.22 μg.ml-1. The detection limits were 0.59 and 0.58 μg.l-1for EPand NE, respectively.Relative standard deviation (RSD) values for two compounds were in the range of1.2-2.1% indicating excellent reproducibility. The proposed method was successfullyapplied to the determination of EPand NE in spiked serum samples after deproteiniza-tion of the samples with acetonitrile. Analytical recoveries from treated serumsamples were in the range of 95-105%.

Drug design is generally achieved through trial and error methods, which is a timeand 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 vasorelaxantactivity (pEC50) of a set of benzopyrane compounds. We used the HyperChemsoftware to extract the molecular features of these compounds (51 molecules);then these features were used to generate the Box-Jenkins model. The dataset wasdivided into three groups: 37 for training, 9 for prediction and 5 for validation. Theabsolute relative deviation of the predicted values was 4.8% and 4.1% for validationand predicton sets, respectively. The correlation coefficient between the predictedpoints and the experimental values was 0.9657, revealing that the proposed modelis capable of representing pEC50 of benzopyranes and could be used to speed updrug discovery processes.