Iranian Journal of Pharmaceutical Research
Volume:6 Issue: 2, Spring 2007

The aim of this study was to prepare liposomes of acyclovir (ACY) by thin layer evaporation (TLE) and reverse phase evaporation (REV) methods. Twenty-seven batches of liposomes from each method were prepared using technique of three variables at three levels (33) factorial design. Drug/Lipid (molar ratio), hydration volume and hydration time were considered three independent variables in TLE method while that of Drug/Lipid (molar ratio), organic phase volume and aqueous phase volume in REV method. Liposomes, obtained by TLE method (TLEs) and REV method (REVs) were evaluated for geometric mean diameter, and percent drug entrapment (PDE). REVs of 3.5(2.3) µm with 77.2% and of 3.4(2.2) µm with 71.1% drug entrapment was obtained with Drug/PC/CHOL (in molar ratio) of 1:4:0.5 and 1:2:0.5 respectively while TLEs of 4.3(1.7) µm with 79.5% drug entrapment was obtained with Drug/PC/CHOL (in molar ratio) of 1:20:10. In vitro studies were conducted to compare drug diffusion pattern across the human cadaver skin (HCS) of promising batches of TLEs and REVs. A significantly low (p<0.05) flux [0.628(0.046) μg/cm2/h] obtained by TLEs when compared with the flux [0.785(0.050) μg/cm2/h] obtained by REVs across HCS. The flux values of ACY TLEs and REVs revealed the lamellarity. Low flux in TLEs than REVs across HCS indicated the formation of multilamellar vesicles (MLVs) in TLE method while oligolamellar vesicles (OLVs) with few lamellae surrounding the large aqueous core in REV method. Multilamellarity of the TLEs makes the liposomes to supply drug in more sustained way in the layer of HCS as indicated by high amount of drug deposition (350.7 µg) in the HCS after 72 h of application when compared with drug deposition in the HCS (321.0 µg) for the same period by REVs.Thus, the finding of the study establishes the role of REV method producing OLVs of ACY with high PDE using 5-10 fold less amount of high costing phosphatidylcholine when compared to MLVs prepared by TLE method with insignificant change in PDE but significant change in flux, which affects the release of drug at the target site.

In order to improve particle properties, new processes combining granulation and crystallization are being developed. This work deals with the spherical crystallization process by the quasi-emulsion mechanism applied to carbamazepine, a pharmaceutical drug. The aim of the present study was to produce of spherical grains made of mall crystals of a drug that have adequate properties for direct compression when manufacturing tablets. Crabamazepine was crystallized under different conditions and the obtained spherical crystals were examined in terms of flow properties, particle size analysis, compression and dissolution behaviors. Physical characteristics of the crystals were studied for the morphology of crystals using scanning electron microscope, for the identification of polymorphism by x-ray powder diffraction and for thermodynamic properties using differential scanning calorimetry. The results showed that the agglomerates produced at 5°C under stirring rate of 300 rpm had superior flow than other agglomerates. Further more the results suggest that agglomerates flow and pack smoothly from the hopper into the die and that tablets formed from agglomerates attain uniformity in weight due to spherical shape of the treated samples. The results showed that, generally, the treated carbamazepine samples (agglomerated forms) possessed superior mechanical and better dissolution rate characteristics to untreated crystals. The results of DSC and x-ray showed that untreated sample and agglomerates were form III and form I of carbamazepine respectively.

Paracetamol is a sparingly soluble bitter tasting drug. It is widely used as an analgesic and antipyretic. Complexation of drug with different cyclodextrins (α, β and HP-β-CD) was attempted to improve solubility of Paracetamol. During the drug excipient interaction studies, α, β cyclodextrins elicited analytical interference and showed considerable absorbance at λmax (243.5 nm) of Paracetamol while the ones constituting of hydroxypropyl-beta-cyclodextrin (HP-β-CD) did not show any such interference. Therefore, the present study is concentrated on exploring HP-β-CD as complexing agent. Phase solubility studies showed that complexation of Paracetamol/HP-β-CD at molar ratio 1:1 and showed AL type solubility curve. Complexation was done by various methods like physical mixing, kneading and freeze drying and resulting drug complexes were characterized by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The thermograms obtained showed an endothermic peak for Paracetamol, for physical mixture to some extent for kneaded mixture, but was completely eliminated for freeze dried product (Inclusion complex). Similar results were obtained during IR studies. Therefore, solid inclusion complex of paracetamol prepared by freeze drying method was found to be an ideal complex. The solubility of paracetamol, was significantly increased (six folds of normal solubility) by complexation with HP-β-CD.

The characteristics of manganese and iron binding to human apotransferrin (apo-tf) have been investigated and compared in this study. Both metal ions were taken up by human apo-tf and formed complexes, with the maximum absorbances observed at 410 and 340 nm for manganese-transferrin (Mn-tf) and 465 nm for iron-transferrin (Fe-tf). Addition of manganese (1. 5 µg/ml) to the reaction mixture containing iron and apo-tf, reduced Fe binding to apo-tf by 20 percent, in comparison to the control sample. The binding of both metals to apo-tf appears to be time and pH dependent processes. Using the equilibrium dialysis technique, the binding constant of manganese to apo-tf was also determined. The binding constatnt of Mn to apo-tf was calculated, using the Scatchard plot analysis. The calculated Ka was 3. 1ױ09 M-1. The binding of manganese and iron to human apo-tf has been discussed and compared in this work, using different biochemical techniques.

Based on the accumulated data, FTIR spectroscopy seems to be a highly sensitive tool in cervical cancer diagnosis. We, therefore, employed this technique in a screening type of research here in Tehran. The purpose of this study was to look for the spectral pattern differences between normal and malignant cervix samples in Iranian women. Through formal and informal announcements, all gynecology departments in the educational hospitals of Shaheed Beheshti University of Medical Sciences, as well as private clinics were asked to inform us of any volunteers (healthy or patient) for this research. Ectocervical smears were collected from volunteers with a spatula and then centrifuged to provide a small pellet of cells for FTIR analysis. A small amount of the pellet of cells was placed on a BaF2 window, dried smoothly and placed in the sample holder of the FTIR instrument. For each spectrum, a total of 512 scans at 1 cm-1 resolution were co-added. This grouping of spectra clearly showed changes in the course of the pathologic results obtained for different samples. Under study although we were not able to further categorize and correlate the spectral changes with different pathological states, but a specific FTIR spectral region differentaining between healthy and cancerous patients was detected in the 1000-1200 cm-1 region of FTIR spectra. Wong’s group had also reported that a difference between the FTIR spectra of normal and malignant tissue is possible in this region (Wong et al., Pro. Natl. Acad. Sci. USA 88, 10988‑10992). However, the pattern of our result does not agree with that of Wong. Wong et al. have found some rising peaks for cancerous samples, in this spectral region while we have observed some disappearing peaks in this region of malignant samples. Therefore, the main difference between our finding and that of Wong is that a higher stability has been reported for the DNA backbone in Wong’s study, while no stable bone was do servable in the cancerous tissues of cervix samples that we studied.

In this study using clonidine (a mixed α2 /I1 receptors agonist), tizanidine (pure α2-receptor agonist), rilmenidine (I1 receptor agonist) and yohimbine (α2-receptor antagonist), we tried to clarify the role of imidazoline and α2-receptors in morphine withdrawal syndrome.Morphine-dependence was induced by administration of increasing doses of morphine in mice. After the last administration of morphine, clonidine (0.3 mg/kg, i.p.), tizanidine (1 and 2 mg/kg, i.p.) and rilmenidine (1.5 and 3 mg/kg, i.p.), with / without pretreatment with yohimbine (1 mg/kg, i.p.) were administered 30 min before naloxone (5 mg/kg, i.p.) challenge. Withdrawal symptoms including: jumping, ptosis, piloerection, tremor and diarrhea were recorded. Rilmenidine (3 mg/kg) decreased naloxone-induced jumping and this effect was partially inhibited by yohimbine. Rilmenidine (1.5 mg/kg), tizanidine and clonidine had no significant effect on jumping. None of drugs influenced ptosis. All drugs increased piloerection and decreased diarrhea. Clonidine and tizanidine decreased tremor.We conclude that Imidazoline receptors as well as α2 receptors are involved in morphine withdrawal symptoms and yohimbine as an α2-antagonist can suppress at least some effects of imidazoline agonists. It is suggested that α2-receptors are located down-stream to imidazoline receptors and their blockade can inhibit imidazoline effects.

The present study investigated the possible protective effect of Helicteres isora (Sterculiaceae) bark extracts on certain biochemical markers in streptozotocin (STZ)-induced diabetes in rats. STZ treatment (60 mg/kg/i.p) caused a hyperglycemic state that led to various physiological and biochemical alterations. Blood levels of glucose, urea, uric acid and creatinine, plasma levels of albumin and albumin/globulin ratio and the activities of diagnostic marker enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ -GT) in plasma, liver and kidney were markedly altered in STZ diabetic rats. Oral administration of H. isora (100, 200 mg/kg/p.o) for 21 days restored all these biochemical parameters to near normal levels. Thus, the present results have shown that H. isora bark extract has the antihyperglycemic effect and consequently may alleviate liver and renal damage associated with STZ-induced diabetes in rats

Antimicrobial activity of the roots of Eranthemum roseum (Vahl) R.Br. (Dasmuli), were tested against different bacteria (including Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Shigella sonnei, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Pseudomonas aeruginosa) and fungi (such as Candida albicans and Aspergillus niger) by cup plate diffusion method. Minimal Inhibitory Concentration (MIC) values of each active extract were determined. The results obtained showed strong activity of the petroleum ether extract of the roots of plant against the bacteria and fungi used as test organisms..

The leaves of four cultivated Eucalyptus species, Eucalyptus microtheca var. Microtheca F. Muell., Eucalyptus spathulata, Eucalyptus largiflorens and Eucalyptus torquata were collected in spring from Kashan and Isfahan provinces (central region of Iran). After drying the plant materials in shade, their essential oils were obtained by hydro-distillation. The oils were analyzed by capillary gas chromatography, using flame ionization and mass spectrometric detection.Twenty-two components were identified in the oil of Eucalyptus microtheca with 1,8-cineole (34.0%), p-cymene (12.4%), α-pinene (10.7%) and β-pinene (10.5%) as main constituents. Twenty-one compounds were identified in the oil of Eucalyptus spathulata with 1,8-cineole (72.5%) and α-pinene (12.7%) as main components. Twenty-six compounds were characterized in the oil of Eucalyptus largiflorens with 1,8-cineole (37.5%), p-cymene (17.4%) and neo-isoverbenol (9.1%) as main components. Sixteen compounds were characterized in the oil of Eucalyptus torquata with 1,8-cineole (66.9%) α-pinene (13.9%) and trans-pinocarveol (6.3%) as main constituents. The results showed that although the 1,8-cineole was the main component of the essential oils of all Eucalyptus species, but its relative content was higher in the oil of Eucalyptus spathulata and Eucalyptus torquata.

The methanolic extracts of Indigofera aspalathoides (MEIA) and Wedelia calendulaceae (MEWC) were evaluated for their anticancer activity against Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice. On day 1, the extract of Indigofera aspalathoides at a dose of 250 and 500 mg/kg body weight and the extract of Wedelia calendulaceae at a dose of 250 and 500 mg/kg body weight were administered orally and continued for 9 consecutive days. The anticancer activity of MEIA and MEWC were examined by determining the tumor volume, tumor cell count, viable tumor cell count, nonviable tumor cell count, mean survival time and increase in life span in experimental animal models. Both these extracts increased the life span of EAC treated mice and restored the hematological parameters as compared with the EAC bearing mice. Thus, the present study revealed that the MEIA and MEWC showed anticancer activity in the tested animal models.

Due to the limited availability of effective pharmaceutical products and serious side effects of the available therapy for leishmaniasis, search for useful medicinal plants is necessary. Previous studies reported preventative effect of Echinacea against Leishmania infections through immunologic stimulation. Here we tested concentrated ethanolic extract of the root of Echinacea purpurea prepared from Zardband Pharmaceutical Co. for its direct leishmanicidal activity in Leishmania culture. Leishmania major promastigotes (stationary phase) were cultured in different concentrations of the extract (0.5–125 mg/ml) for 30 min. Then the extract was removed and cell viability was determined during 120 h. LD50 for the promastigotes were determined as 22.3, 16.7, 3.66, 1.98 and 1.23 mg at 8, 16, 24, 48 and 72 h respectively. The results showed the irreversible leishmanicidal activity of the E. purpurea. Although all concentrations of the extract had antileishmanial effect, we suggest using this crude extract in concentrations of 50 mg/ml and more for application in related medicinal targets.