Iranian Journal of Pharmaceutical Research
Volume:7 Issue: 4, Autumn 2008

The aim of this investigation was to prepare, characterize and optimize the aceclofenac proniosomes using central composite design and carry out stability studies. Three independent variables selected were molar ratio of drug to lipid (X1), surfactant loading (X2) and volume of hydration (X3). Based on central composite design, 16 batches of proniosomes were prepared by slurry method and evaluated for the percentage drug entrapment (PDE) and mean volume diameter (MVD). The PDE and MVD (dependent variables) and the transformed values of independent variables were subjected to multiple regressions to establish a second order polynomial equation. Contour plots were constructed to further elucidate the relationship between the independent and dependent variables. The conformity of the polynomial equations was checked by preparing three checkpoint batches. From the computer optimization process and contour plots, predicted levels of independent variables X1, X2, and X3 (-0.77, -0.8 and 0 respectively), for an optimum response of PDE with constraints on MVD were determined. The optimized batch was subjected to stability studies. The polynomial equations and contour plots developed using central composite design allowed us to prepare proniosomes with optimum responses. Proniosomes stored refrigerated and at room temperature, were both found to be stable.

Frequent dosing of the potent anti-androgen, flutamide, is necessary to reach a therapeutic level for the treatment of prostatic carcinoma. Sustained delivery of the drug could reduce the adverse effects such as gastrointestinal disorders and improve patient compliance. In the present study sustained-release matrix tablets of flutamide were prepared by direct compression method using different polymers. Cellulose ethers (HPMC and NaCMC), natural gums (guar and xanthan gums) and compressible Eudragits (RSPO and RLPO) and their combinations were used in different ratios to examine their influence on tablet properties and drug release profile. Tablets were evaluated by measurement of hardness, friability, content uniformity, weight variation and drug release pattern. All the tablets met the pharmacopoeial requirements for physical tests, based on USP 29. Almost in all formulations, with increasing the percentage of polymer, release rate decreased, though drug release pattern was mainly dependent on the type of polymer. Formulations H2F4 (contained 25% HPMC) and S3F4 (contained around 40% RSPO) met the desired requirements for a sustained-release dosage form. These two formulations released their drug content with a first order kinetic.

The objective of the current study was to develop and optimize a sublingual tablet formulation of captopril which is an effective drug in the treatment of hypertension. Captopril containing tablets were prepared by direct compression method using different ingredients such as polyvinyl pyrrolidone، starch 1500، sodium starch glycolate and lactose (independent variables) and magnesium stearate، talc and aspartame (fixed components). Tablets were evaluated for the physical properties including hardness، disintegration time and friability which were considered as responses in a D-optimal experimental plan. Results were statistically examined using special cubic model and polynomial mathematical equations and found to be statistically significant (p<0. 05) for disintegration time and friability data. Meanwhile linear model was best fitted with hardness data. The obtained results were used to generate optimized overlay plot. The physical data from the numerical optimization were verified and found to be very close to those predicted from the regression analysis. Additional experiments including drug content، in vitro drug dissolution rate and accelerated stability studies were also performed on the optimum formulation. All results were in accordance with the requirements of a sublingual tablet.

Infant formula has a fatty acid composition that meets the needs of the neonates for unsaturated fatty acids.These fatty acids are of major importance during this period of life in which the brain and retina are developing, and will therefore have an influence upon visual acuity and learning abilities.Oxygen reacts readily with unsaturated fatty acids, so that every time these compounds are handled there is a danger of contaminated with oxidative products. Oxidative stability is an important parameter in characterization of fats and oils.The purpose of this study was to predict the shelf life of an infant formula using accelerated stability test (rancimat), to save time. The Rancimat method is based on conductometric determination of volatile degradation products and features automatic plotting of the conductivity against time. The evaluation was performed graphically after completion of the experiments.The stability of a commercially available infant formula in Tehran, Iran was measured using rancimat method at temperatures of 60, 80, 90, 100, 110, 120 and 130 °C.Equations have been derived by which the shelf life can be predicted on the basis of the Rancimat method, thus avoiding the time-consuming long-term studies. The shelf life of the commercial infant formula studied was estimated as 534 days (approximately 18 months).

Due to high resolution power of sulfated cyclodextrins (HS-CDs), utilization of these selectors for chiral resolution of 7 basic and 2 zwitterionic drugs have been examined. Experiments were performed on a HP3DCE instrument equipped with an on-column diode array UV absorbance detector. Fused silica capillaries with an inner diameter of 50 μm, an outer diameter of 365 μm, and a total length of 45.5 cm (8.5 cm to the detector) were used. Capillaries were rinsed with PEO once daily. To reduce analysis time, short-end injection technique was applied. The electrophoretic conditions for the stereoselective analysis of drugs were in the carrier mode with 25 mM sodium phosphate buffer containing 1.25% w/v of each HS-CD at pH 2.5 with an applied voltage of +15 kV. At these conditions, rapid enantioresolution(≤3.9 min) of all drugs were achieved.

Black seed (Nigella sativa) is considered as a biological response modifier. Thymoquinone (TQ) is the bioactive and the most abundant constituent of the volatile oil of this seed which has been shown to possess anti-inflammatory, antioxidant and anti-neoplastic effects. In this study, the effect of TQ on HepG2 cell line was investigated in an attempt to identify its potential mechanism of action. Cell viability and proliferation were assessed in presence of different concentrations of TQ, which revealed a remarkable inhibition of HepG2 cells by TQ in a dose dependant manner. TQ ability to induced apoptosis was determined by Flowcytometry and colorimetric measurement of Caspases 3 and 9. The apoptotic effect of TQ was much more dramatic after 12 h treatment and the activity of Caspases 3 and 9 was increased. Also, Flowcytometric analysis of cell cycle revealed an early G1/S arrest of cells, which is characteristic of apoptosis. It could be concluded that Thymoquinone is a promising anti-cancer agent for hepatocellular carcinoma.

During the last two decades, various medicinal plants have been studied for their possible antimicrobial activity to discover new antimicrobial agents capable of resolving problems such as the development of drug resistance in pathogenic microorganisms as well as the side effects of some present antibiotics. In this study, the antibacterial activity of methanolic extract of T. pubescens (rich in flavonoids) was investigated.The aerial parts of the plant were collected from Alvand mountainside (Hamadan, Iran) in May 2005 and identified by Hamadan Natural Sources Organization. The air-dried plant materials were ground to fine powder and then extracted by soxhelet apparatus using methanol. The extract was tested at a concentration of 100 mg/ml against a panel of Gram-positive and Gram-negative bacteria using the disk diffusion technique. This methanolic extract demonstrated antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Streptococcus pyogenes, Enterococcus faecalis, Vancomycin-resistant E. faecalis (VRE) and Micrococcus luteus, and produced inhibition zones with 8-16 mm diameters. However, it showed no activity against Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa and Salmonella spp. Minimum concentrations (MC) of the extract forming a clear zone were determined against susceptible bacteria. MC90 of the extract against 10 MRSA strains tested was 1.56 mg/ml, indicating its good activity against this important nosocomial pathogen. T. pubescens seems to be a good candidate for further phythochemical studies in an attempt to find new chemical entities combating resistant bacteria.

α-Amylase inhibitory activities of ethanol extracts from six selected Iranian Salvia species (S. hydrangea DC., S. hypoleuca Benth., S. officinalis L., S. reuterana Boiss., S. verticillata L. and S. virgata Jacq.) were examined, using in vitro model. In addition, antioxidant capacities (DPPH• radical scavenging) and total flavonoid cotents of the extracts were also determined. The results showed that the extracts of S. verticillata and S. virgata, significantly and concentration dependently, inhibited α-amylase activity. All the extracts exhibited antioxidant activities, among which S. verticillata, S. virgata, S. officinalis, S. hypoleuca and S. hydrangea were found to be the most active in terms of assay. S. hypoleuca and S. reuterana extracts had the highest total flavonoid contents. However, a favorable correlation was not found between α-amylase inhibitory effects or antioxidant activities and the total flavonoid contents of the extracts.

The objective of this study was to determine the frequency of microorganisms isolated from blood samples of patients admitted to Intensive Care Unit (ICU), and the rate of their resistance to common administered antibiotics in an Iranian ICU. One-hundred patients with Systemic Inflammatory Response Syndromes (SIRS), hospitalized in ICU of Sina Hospital, Tehran, Iran, were entered to this cross-sectional study from March 2005 to March 2006. Blood samples were taken from these patients and transferred to culture medium. After detecting the type of microorganism, minimum density for inhibition of growth of microorganisms by antibiotics, using minimum inhibitors concentration (MIC) method, was determined for ceftazidime, ceftriaxone, amikacin, ciprofloxacin, meropenem and cefepime. Culture results of 38 patients were positive (38%). Klebsiella (14 patients, 37%), coagulase negative Staphylococcus (9 patients, 23.6%), Pseudomonas and Acinetobacter (each of them recovered in 6 patients, 15.8%), Staphylococcus aureus (one patient, 2.6%) and gram positive bacilli (2 patients, 5.2%) were detected microorganism. Only Staphylococcus aureus was resistant to all studied antibiotics. Gram-negative bacilli showed resistance to all antibiotics except for amikacin and meropenem.The rate of septicemia detected was higher in comparison to developed countries. Clinical suspicion with appropriate microbiological tests is essential for early diagnosis to prevent adverse outcomes in patients admitted to ICU.