Iranian Journal of Pharmaceutical Sciences

A major hurdle in pharmaceutical formulation is water insolubility of most of drugs affecting their stability and bioavailability. If the drug is also insoluble in organic medium, it is difficult to deliver it in a sufficiently bioavailable form and hence it is a great challenge to formulation researchers to overcome such difficulty. Although some approaches are available for enhancing the dissolution of poorly soluble
drugs, there has been certain draw backs like use of organic solvents, low drug loading and large doses. However, a new solution to poorly water soluble drug candidates is now available, i.e. nanonisation that leads to much more soluble, more biologically available and safer dosage form of poorly soluble and poorly bioavailable drugs. Controlled release of these drugs is also possible by forming nanostructured
matrices. In this article, a brief description of production methods of drug nanoparticles and commercialized methods are presented along with brief overview on second generation of drug nanocrystal (Smart crystal technology), controlled release of hydrophobic drugs and recent works thereof are also presented.

Losartan potassium is a well known orally active non-peptide angiotensin II receptor antagonist. Losartan potassium and its principle active metabolites block the vasoconstrictor and aldosterone secreting effect of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptors. The drug is reported to promote the decrease in ventricular hypertrophy, salt and water excretion and vascular smooth muscle relaxation. Present investigation was aimed at the formulation of transdermal therapeutic system of losartan potassium for effective control over hypertension since the drug shows considerable first pass metabolism when administered through oral route. Blends of hydrophobic and hydrophilic polymers like ethyl cellulose with polyvinyl pyrrolidone and ethyl cellulose with hydroxypropyl methyl cellulose were used in the formulation of the medicated films. Films were prepared using dibutyl phthalate as plasticizer with eighteen different combinations of these three polymers by solvent evaporation technique. Polyvinyl alcohol was used to prepare the backing membrane. Several physicochemical parameters like moisture content, moisture uptake, thickness, film folding endurance, tensile strength, skin irritation and surface morphology of the films were studied. For all the formulations, skin permeation of the loaded drug through albino mice skin was studied using Keshary-Chien diffusion cell. Formulations containing higher proportion of hydrophilic polymers blended with lower proportions of hydrophobic polymer were found less consistent in comparison to the patches comprised of higher proportion of hydrophobic polymer.

Tropicamide is an antimuscarinic agent used as eye drops for refractive examinations. The aim of this study was to develop a simple and suitable analytical method for determination of tropicamide in eye drops in the presence of excipients. A zero-crossing third and fourth derivative spectrophotometric method was described for determination of tropicamide in eye drops. The measurements were carried out
at wavelengths of 263.8 and 255.4 nm for third- and fourth-derivative, respectively. The method was found to be linear (r2> 0.999) in the range of 10-100 µg/ml for tropicamide in the presence of excipients. The limit of determination was 10 mg/ml for tropicamide. The method was successfully applied for determination of tropicamide in eye drops without any interference from excipients or need to prior separation before analysis.

Reaction of 5-phenyl tetrazole with ethyl chloroacetate to form ethyl (5-phenyl-1H-tetrazol-1-yl) acetate (1). Compound 1 react with hydrazine hydrate in ethanol yield 2-(5-phenyl-1H-tetrazol-1-yl) acetohydrazide (2). The condensation of (2) with various aldehydes yield the corresponding substituted N'-[-arylidene]-2-(5-phenyl-1H-tetrazol-1-yl) acetohydrazide (3a- j). The compounds obtained were identified by spectral data and have been screened for antimicrobial activity. The most promising compounds having good antibacterial activity were 3b, 3c and 3i, and the best for antifungal activity were 3b, 3c and 3e.

This study presents the influence of hydroxypropyl-ß-cyclodextrin (HPBCD) on the aqueous solubility of acyl esters of cyproterone. First, a number of esters of cyproterone were synthesized. Then the phase solubility analysis of the compounds in the presence of HPBCD was investigated in phosphate buffer solution at a pH of 7.4. To gain a better understanding of the complexation mechanism, the synthesized
compounds were docked inside the HPBCD cavity using the Autodock program. The results show that the interaction between the synthesized compounds and HPBCD is of type AL and all of the compounds exhibited higher solubility as a result of complexation with HPBCD. The extent of increase in solubility was consistently greater as the ester chain length ascends by 4 carbon atoms. This increase in solubility is in agreement with the results obtained by calculating docking scores.

The effects of hydroalcoholic extract (HE) of Curculigo orchioides Gaertn. rhizome (Hypoxidaceae) and its alkaloidal and non-alkaloidal fractions (AF) and (NAF) were evaluated in carrageenan-induced paw edema experimental models of inflammation. The oral administration of HE, their AF and NAF fractions were used at doses of 100, 300 and 500 mg/kg. The effect produced by the HE, AF and NAF fractions were comparable to that of indomethacin with a dose of 10 mg/kg as the reference drug. The percentage of inhibition of inflammation of all extracts was dose dependent. The crude HE showed 22.45%, 35.62% and 39.03% inhibition; AF showed 31.68%, 36.89% and 41.17% inhibition; and NAF showed 28.34%, 34.49% and 37.43% inhibition of induced hind paw edema in rats at doses of 100 mg/kg, 300 mg/kg and 500 mg/kg, respectively, while indomethacin inhibited 48.66% of the edema. The acute toxicity evaluation showed that all extract were not toxic up to 2000 mg/kg (p.o). The results suggest that the anti-inflammatory effects of the extracts as claimed in folk Indian medicine.

This paper describes 3D-QSAR analysis and biological evaluation of 1,5-benzodiazepine analogues. Benzodiazepine nucleus with its simple structure gives a good opportunity for further modification regarding an increase of its antimicrobial activity. We synthesized a series of benzodiazepine analogues from condensation of various chalcones and halo substituted o-phenelynene diamines. All compounds were assayed in vitro against, E. coli, P. aeruginosa, S. aureus. The models were generated on the Vlife MDS 3.5; selected models showed a correlation coefficient (r2) above 0.9 with cross-validated correlation coefficient (q2) above 0.8, respectively, for all the selected organisms. The 3D-QSAR models generated were externally validated for all models using a test set of 6 molecules for which the predictive r2 (r2-pred) was found to be above 0.45. The results of 3D-QSAR indicate that contours can be used to design some potent antibacterial agents.

Pharmacy as the last unit in the pharmaceutical supply chain is responsible for supplying and dispensing medicines to the patients and giving required advices to them, based on their needs and physician’s prescriptions according to standard protocols of the country. Beside this responsibility, which is primarily on drugstores, this unit is regarded as a small business unit and should have economical feasibility
and acceptable profit, so that it’s main responsibility will not be negatively affected by unfavorable economic situation. In this study, the profitability of pharmacies, in case they merely supply medicine and work out no other business, has been put into consideration. To carry out the research, case studies and interviews along with archival reviews and historical records have been used and income statement of case
pharmacies has been inspected. The results show that in the case that Iranian pharmacies simply supply medicines, they will be loss-baring and to improve them and increase their outcome some measures need to be taken. Some recommendations have been offered in the discussion and conclusion section of this paper.

Random samples from asymptomatic leaves and branches of five native medicinal plants: Stachys lavandulifolia, Rumex pulcher, Hypericum scabrum, Starja bachteriarica and Achillea kellalensis were collected from Chaharmahal province of Iran and examined for the presence of endophytic bacteria and fungi with biological activity. From 8 isolated endophytic fungi, all displayed considerable activity against at least one indicator fungi. Fungal isolates from R. pulcher leaves and branches showed activity against Aspergillus niger, Penicillium spp, Alternaria spp and S. aureus. Five Bacillus spp strains were isolated from R. pulcher leaves and branches, four (80%) showed activity against S. aureus, and two strains were active against all indicator fungi. Bacillus spp strain isolated from leaves of H.scabrum was active against S. aureus and all 3 indicator fungi. None of the isolated endophytes showed antibacterial activity against E- coli.