Iranian Journal of Pharmaceutical Sciences
Volume:1 Issue: 4, Autumn 2005

The purpose of this study was to prepare and characterize microspheres loaded by cyclosporine A(CyA)-cyclodextrin (CD) complex. To achieve this goal, PLGA microspheres loaded by CyA CD complex were prepared by multiple emulsificationsolvent evaporation methods.Morphology, size, encapsulation efficiency and drug release from these microspheres were evaluated. Microscopic evaluation of microspheres showed that microspheres were spherical in shape. The size analysis results indicated that size range varied from 1 to 50 mm for complex loaded microspheres. Encapsulation efficiency of microspheres was increased by increasing drug to polymer ratio. Drug release was found to be biphasic with a first more rapid release phase (burst) followed by a slower phase. After two weeks, 43.40%±3.45 of CyA was released from these microspheres. In conclusion, microspheres loaded with CyA-CD complex were prepared that could be used for control delivery of CyA.

In this study, the stability of trinitroglycerin (TNG) in polyethylene (PEG) 400 was investigated according to Arrhenius approach. The reaction rate constant (k) for the thermal disintegration of TNG in PEG 400 at various temperatures was counted based on the percents of remaining TNG at different intervals of time at a specific temperature. The results showed that “k” at 40, 50, 60, 70, 80 and 90 ºC were 6.5x10- 4,3.57x1 0- 3, 4.7x1 0- 3, 3x1 0- 2, 6.2x10- 2 and 6.5x1 0- 2, respectively. By plotting “log k” against temperature (1/T), “k” was obtained at 5 and 20 oC which was 1.47x10- 5 and7.94x10-5, respectively. The results showed the time required to attend 90, 80, 70, and 50 percent of the original TNG at 5 oC was 9.76, 20.7, 33, and 64.2 months, respectively. The results assist in the calculation of the expiration time of TNG/ PEG 400.

In this study, the pharmacokinetic parameters of two marketed tablet formulations of ketoconazole were studied, and the relative bioavailability of the test formulation was compared with a reference formulation. A single dose (12x2) double blind randomized cross-over study of a generic formulation of ketoconazole tablet (2x200 mg), and a commercial brand, Nizoral tablet (2x200 mg, Janssen Pharmaceutica Beerse Belgica) was carried out. All of the tablets met the United States Pharmacopoeia dissolution specifications. The plasma level of ketoconazole was determined by using a modified rapid and selective reverse phase HPLC method. Plasma data was used to evaluate the relative bioavailability and other pharmaco-kinetic parameters characterizing rate [peak plasma concentration (Cmax) and time of peak concentration (Tmax)] and the extent of absorption (AUC). The mean peak plasma concentration (Cmax) of ketoconazole of the two different formulations, A (reference) and B (test), were 7.08±2.81 and 6.74±2.20 mg/l at 1.70±0.48 h and 1.73±0.75 h, respectively. The mean AUC0 −∞ of the two products, were 39.07±16.25 and 31.85±14.64 for Aand B, respectively. Statistical analysis showed no significant d i fferences between various pharmacokinetic parameters of the two diff e r e n t formulations. The 90% parametric confidence intervals for the mean of test/reference ratios of Cmax, AUC0-12,AUC0−∞ and Cmax/AUC0−∞ were within the bioequivalence acceptable range (80-125%). Results of this study showed that the extent and rate of absorption of ketoconazole tablets tested are comparable and the generic formulation is bioequivalent to the commercial product.

The essential oil of Peucedanum ru t h e n i c u m fruits, obtained by hydrodistillation, was analyzed by gas chromatography and gas chromatography mass spectrometry. Among the 31 identified constituents accounting for 83.9% of the total oil, the major components were 1,8-cineole (11.15%), camphor (5.86%), Z-carveol (6.88%), l-carvone (5.61%), 8,9-dehydroisolongifolene (11.35%), caryophyllene oxide (13.65%), and caryophylla-4(12),8(13)-dien-5-β-ol (5.19%). Antimicrobial activity of the essential oil was investigated against various gram-positive and gram-negative bacteria. The essential oil of P. ruthenicum showed activity against gram-positive bacteria but had no effect on the tested gram negative bacteria.

Research advances during recent years offer new insight into therapy and the prevention of gastrointestinal ulcers by using medicinal plants. Flavonoids, tannins, triterpenoids, fatty acids and essential oils are among the most effective herbal constituents that have potential antiulcerogenic properties, and most of them could be found in Zataria multiflora. Z. multiflora is one of the indigenous plants of Iran, which is readily available and traditionally used to improve gastrointestinal disorders. In a recent trial, we decided to study the potential antiulcerogenic effects of the plant on an animal model of duodenal ulcer. Hydroalcoholic extract of the plant with doses of 200, 400, 800 and 1200 mg/kg, ranitidine (50 mg/kg), sucralfate (2 g/kg) and 1 ml of the vehicle were administered orally to different groups of male Wistar rats. Two other groups received (i.p.) vehicle (1 ml) and extract (800 mg/kg). Duodenum ulcers were induced by cysteamine HCl and the number of ulcers, area, and finally ulcer index were assessed. Ranitidine and sucralfate resulted in significant reduction in the duodenal mucosal damage for the entire ulcer factors assessed. Increasing doses of the extract resulted in a significant reduction in ulcerated area and index in a dose dependent manner. We concluded that Z. multiflora extract was effective in protecting against duodenal ulceration, and for the larger doses used, the efficacy was comparable with the reference drugs. The mechanism of action couldn’t be clearly proposed for the plant extract, however; the local mucosal enhancement and cytoprotection may be involved.

The oxidative hemolysis of rat erythrocytes induced by 2,2’-azobis–(2-amidinopropane) (AAPH) and its inhibition by rosemary essential oil was studied. Different concentrations (0.178, 0.357, 0.534 and 0.712 ml/ml) of the essential oil showed no significant hemolysis compared to phosphate buffer solution. AAPH (25 mM and 50 mM) induced hemolysis in a time-dependent manner. Diff e r e n t concentrations of the essential oil inhibited hemolysis induced by 25 mM AAPH. However, in the presence of 50 mM of AAPH, only the two higher concentrations (0.534 and 0.712 ml/ml) of the essential oil inhibited hemolysis. Addition of essential oil 2 or 3 h after incubation with AAPH had no significant effects on the time course of cell lysis. It is concluded that, in addition to its well-established antioxidant effects, rosemary essential oil displays cytoprotective properties.

Diethylstilbestrol (DES) was widely used in the past, as the morning after contraception, but its application became extremely limited due to several complications including delayed clear cell adenocarcinoma in female infants. However, the use of DES increased during the past decade for hormone replacement therapy. The aim of this study was to investigate possible teratogenicity of this synthetic oestrogen. The experiment was conducted on N-MRI mice. Va r i o u s concentrations of DES were administered i.p. to pregnant animals throughout the period of organogenesis (days 9 and 10 of pregnancy). The control group received ethanol as vehicle. Pregnancy was terminated on the 18th day by cervical dislocation. The embryos were then removed and fixed in Bouin’s solution, and parameters currently used in teratogenic studies were assessed. Severe embryo toxicity score was observed following the application of DES at doses of 200 and 400 mg/kg (71.4% and 83.6%, respectively). The weight and the average size of some of the examined parameters were markedly decreased by embryological observation. Furthermore, the size of derm and mosaic cells of urinary bladder, shortening in the length of femur, and abnormal disposition of calcium compound in embryos were markedly different in the treated mice.

This Study was performed to evaluate the effect of atenolol on the serum concentration of TT4 and TT3 in subclinical hyperthyroid patients. Due to the i n s u fficient information about the effect of atenolol on serum level of these hormones, the aim of this research was to shade some light on the subject. Fifteen subclinical hyperthyroid patients entered this study. Each patient received 100 mg/day atenolol. The serum concentration of atenolol, TT4 and TT3 were measured before starting the administration of the drug and on the first, third and seventh day after atenolol administration was started. The serum concentrations of TT4, but not TT3, on the third and seventh day were increased significantly in comparison to the baseline TT4. There was no correlation between plasma atenolol concentration and changes in TT4 and TT3.