Iranian Journal of Pharmaceutical Research
Volume:7 Issue: 3, Summer 2008

Microencapsulation has become a common technique in the production of controlled release dosage forms. Many results have been reported, concerning the use of alginate beads as controlled release drug formulations. Alginate has a unique gel-forming property in the presence of multivalent cations, in an aqueous medium. Ibuprofen is an excellent analgesic and antipyretic, non-steroidal anti-inflammatory agent with a high therapeutic index. Formulation of ibuprofen in beads could reduce its gastric ulcerogenicity. Hence, in this study the formation of Ca-alginate ibuprofen beads, through ionotropic gelation has been investigated.For this purpose, different cross- linking agents including: Ca2+, Ba2+, Mn2+, Co2+, Sn2+ and Pb2+, were used for bead preparation. Next, characterization of the beads, size distribution, encapsulation efficiency of ibuprofen within the beads, the bead swelling and the drug release kinetic were investigated.Results showed that only Ca ion is suitable for the formation of ibuprofen beads. A good swelling profile for beads in phosphate buffer (pH=7.4) and the lack of swelling in hydrochloric acid (pH= 1.2), show the suitable nature of the beads. In addition, formulation of Na-alginate (2%) and Ca-chloride (2%) beads,resulted in an encapsulation efficacy of around 90%. The drug release studies showed a rapid and complete ibuprofen release from the beads, specially those prepared from Na-alginate (2%) and Ca-chloride (2%), in phosphate buffer medium.However, no detectable drug release was observed within the acidic medium.In conclusion, ibuprofen is capable of being n be microencapsulated as a bead formulation, with suitable properties and release profile.

Oral Lichen Planus (OLP) is a chronic inflammatory disease of oral mucosa, with an immunological origin. Atrophic/erosive OLP needs appropriate treatment, due to the pain and malignancy potential. Topical corticosteroids are the most effective drug therapy and mouthwashes are more effective topical dosage forms for this purpose. However, at present there are no corticosteroid mouthwashes available in Iran. In this study, the efficacy of a new mouthwash containing clobetasol, ketoconasole and amitriptyline was evaluated in comparison to the common treatment.In this double blind randomized clinical trial study, 50 patients who had inclusion criteria were grouped randomly, with no difference in demographic data. The experimental group was treated using 5ml of mouthwash four times a day for 5 min, while the control group was treated by dexamethasone tablet, nystatin drop and diphenhydramine syrup. Severity of the lesions and pain were followed as the chief complain and recorded in the initial, 1, 2, 4, 8 and 12 weeks intervals. All the collected data were analyzed with the Chi-Square, Mann-Whitney, student T-test and Mantel-Cox statistical tests, using the SPSS version 13 softwares.There were significant differences in the pain reduction in the 1st (P<0.001), 2nd (P=0.01) and 12th (P=0.025) weeks between the two groups, but the difference in weeks 4 (P=0.058) and 8 (P=0.131) were not significant. The lesion reduction was significantly higher in the experimental group (P<0.001). Complete resolution of lesions occurred on average after 2.65 and 10.75 weeks for the experimental and control groups, respectively. Also most patients in the experimental group (70.6%) had complete subjective satisfaction (75-100%) of treatment but most patients (43.8%) were mildly satisfied (0-25%) in the control group. Survival analysis showed that the possibility of existence of lesions after 3 months in the experimental group and control groups were 0% and 100% (P<0.001), respectively.In conclusion, it seems that the new mouthwash is more effective in short term, with greater convenience for the patients.

The potential to cause tissue damage by metal ions is the matter of widespread investigation. Titanium salts are widely used in industry for ceramic painting, in pharmacy for tablet coating and making chemical sunscreens and in medicine as photo catalysts with bactericidal activity. This may address the idea that the exposure to these salts could play a role in metabolic disorders. In this study the effect of Ti on liver contents of lipid fractions was investigated. Male Wistar rats (200-250 g) were used for the experiments. Groups of animals were injected for 10 days with 2.5 mg/kg of titanium chloride, as acute dose and for 30 and 60 days with 0.75 mg/kg as chronic doses. At the end of the experimental period animals were anaesthetized, the abdomens were opened and the livers were perfused with appropriate buffer. Livers were then removed immediately and used fresh or kept frozen until the analysis. Livers were then homogenized and their contents of triglycerides and phospholipids were determined. Blood samples were also collected before killing to measure the lipid levels.Titanium led to a significant increase in phospholipid content of the liver (about 66 %) whereas triglycerides decreased by about 25 to 30 percent in all treated animals. Titanium also reduced plasma free fatty acids and triglycerides significantly but cholesterol and LDL levels were increased in all treated animals. Lipoprotein lipase activity was also inhibited in titanium treated animals.In Conclusion This study is significant because it shows that chronic inhalation or exposure to titanium at workplaces is associated with changes in liver lipid metabolism. Plasma lipid-related parameters were also affected. Although less information is available concerning the mechanism of toxicity but the induction of reactive oxygen species production may be responsible for this effect.

In addition to its effect on reproductive organs, estrogen exhibits complex effects on brain structure, function and behavior. In this regard, the influence of gonadal hormones especially estrogens on nociception has recently been accepted. Soybean is known as an important phytoestrogen containing plant that is used as an alternative for estrogen replacement therapy. In this study, the influences of soy extract and estrogen on formalin-induced nociception in male rats were examined. In the first experiment, the effect of soy extract added to drinking water (60 mg/kg per day) on the nociception was assessed and compared with a control group (with soy-free drinking water). There was a significant decrease in nociception in rats that received soy extract for two weeks. Furthermore, different doses of soy extract (50, 150 and 200 mg/kg) were injected subcutaneously 30 min before formalin test to assess its effect on acute and chronic pain perception. It was observed that different doses of soy extract had similar antinociceptive effects that were significantly different from saline injected control group. In other experiment, rats treated with a single dose of 150 μg of 17-β estradiol (s.c.) 48 h prior to the formalin test, to be compared with a control group just received estrogen vehicle (DMSO). Acconding to our results Estradiol did not show any significant effect on pain suppression. These results suggest that the antinociceptive effect of soy extract on chronic pain is not aresult of its phytoestrogenic activitiy, it might atherefore be related to other substances within soy extract.

The ameliorative activity of aqueous extract of the flesh of dates (Phoenix dactylifera L.) and ascorbic acid on thioacetamide-induced hepatotoxicity was studied in rats. Sixty male rats were divided into six equal groups of 10. Two groups were controls, one treated with thioacetamide and one with only distilled water. Two groups received extract of flesh Phoenix dactylifera and intraperitoneal (IP) thioacetamide (400 mg/kg) either before or after administration of flesh extract. Two groups received ascorbic acid and intraperitoneal (IP) thioacetamide (400 mg/kg b.wt.) either before or after administration of ascorbic acid. Liver damage was assessed by estimation of plasma concentration of bilirubin and enzymes activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), γ glutamyl transferase and alkaline phosphatase and serum alpha fetoprotein and serum total testosterone. Treatment with aqueous extract of date flesh or by ascorbic acid significantly reduced thioacetamide-induced elevation in plasma bilirubin concentration and enzymes. This study suggests that thioacetamide-induced liver damage in rats can be ameliorated by administration of extract of date flesh and ascorbic acid.

The aim of the study was to evaluate the antioxidant and free radical scavenging properties and to determine the phenolic content of the ethanol extract from five Mentha species [M. longifolia (L.) Huds., M. piperita L., M. pulegium L., M. rotundifolia (L.) Huds., and M. spicata L.]. The antioxidant activities of the extracts were investigated with two different methods, 2,2’-diphenyl-1-picrylhydrazyl radical (DPPH•) and 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+). M. piperita exhibited the strongest activity as a DPPH• scavenger. On the other hand, all the extracts were active in the ABTS•+ assay and no significant difference was observed in this assay. The total phenolic content (TPC) of the extracts was determined by Folin-Ciocalteu method and M. piperita showed the highest TPC. A high correlation was found between the DPPH• scavenging potency and the total phenolic content of the extracts (r2 > 0.989).

Ethanolic extract of leaves of Elaeocarpus ganitrus was analyzed for their total antioxidant capacity, reducing power, metal chelating, ABTS+ (2, 2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical scavenging and hydroxyl radical scavenging activities. The extract at 500 μg/ml showed maximum Iron chelating activity (76.70%) followed by the scavenging of the ABTS+ radical (55.77%) at the same concentration. However, the extract showed only moderate hydroxyl radical scavenging activity (13.43%). Total antioxidant capacity was found to be 24.18 mg ascorbic acid equivalents at 500 µg/ml extract concentration. There was a positive correlation between the total phenolic content and antioxidant capacity, R2 = 0.8547, whereas the correlation between the total flavonoids and antioxidant capacity was determined to be R2=0.8413. The results suggest that phenolics and flavonoids in the leaves provide substantial antioxidant activity.

Methanolic extract of Solanum trilobatum Linn. (MEST) belonging to the family of Solanacea was evaluated by hot plate and acetic acid induced writhing methods to assess its analgesic activity. The extract was also evaluated for its anti-inflammatory activity by subjecting into carrageenan, and cotton pellet induced granuloma tests for its effect on acute and chronic phase inflammation models in rats, as well as analgesic activity in mice. It was found that the extract caused an inhibition on the writhing response induced by acetic acid in a dose dependent manner. 300 mg/kg doses of MEST and indomethacin could block the writhing response by 46.68% and 73.73% (p<0.05), respectively. It was also indicated that the MEST showed significant (p<0.001) antinociceptive action in hot plate reaction time method in mice. This effect was comparable to that of standard drug pentazocine treated controls, suggesting the central activity of MEST. Maximum inhibition (56.71%) was obtained at a dose of 100 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas indomethacin (standard drug) produced 57.65% of inhibition. In the chronic model (cotton pellet induced granuloma) the MEST 300 mg/kg, indomethacin and dexamethasone standard drug showed decreased formation of granuloma tissue by 21.48%, 29.63% and 34.84%, respectively. The results indicate the potent analgesic and anti-inflammatory effects and therapeutic efficacy of Solanum trilobatum extract on animal models which are comparable with those of standard drugs such as pentazocine, indomethacin and dexamethasone, respectively.

The monitoring and reporting of adverse drug reactions (ADRs) in hospitals aims to identify and quantify the risks associated with the use of drugs. The present study was performed to characterize the rate and the pattern of ADRs, due to cardiovascular drugs and anticoagulants, in a tertiary care teaching hospital. For this purpose, all the patients treated with cardiovascular drugs and anticoagulants in the post coronary care unit (CCU) from September 2006 until January 2007 were actively monitored for ADRs. Data evalution was conducted for various parameters which included patient demographics, number of prescribed drugs, drug and reaction characteristics, and outcome of the reactions. Assessment was also done for causality, seriousness, and preventability. A total of 64 ADRs during the 4 months study period were evaluated. The overall rate of ADRs calculated from the patient population was 53%. No significant difference was seen in the overall rate of ADRs in males vs. females. The most commonly affected organ was gastro-intestinal system (14.06%). Nitroglycerin tablet (long-acting) and digoxin were the drugs most frequently reported (28.28%). In 20.31% of the reports, the patient had recovered from the reaction at the time of data collection. Upon causality assessment, the majority of the reports were rated as probable (64.06%). Serious and non-serious reactions accounted for 3.13% and 96.87% of the ADRs, respectively. In 9.37% of the reports, reaction was considered to be preventable. Our data revealed that ADRs in the post CCU occur rather frequently during hospitalization. Such studies enable us to obtain information on the rate and pattern of ADRs in the local population. These evaluations need to be followed by dissemination of the information to healthcare professionals to improve the quality of patient care and ensure safer use of drugs.

In the present study, the effect of steroidal anti-inflammatory drug betamethasone (0.12, 0.24 mg/kg, i.p. acutely) on striatal glutamate level in Parkinsonian rats was studied using the microdialysis technique. Our results showed significant differences (p<0.05) in the level of striatal glutamate between treated and non-treated damaged rats.