Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

The effect of Boswellia Serrata on neurorecovery following diffuse axonal injury.

OBJECTIVES: This pilot trial was conducted to establish whether Boswellia Serrata (BS), a traditional herbal medicine, could improve the outcome of patients who have diffuse axonal injury (DAI). METHODS: In total, 38 patients with pure DAI were enrolled in this 12-week, double-blind, randomized, cross-over study. The patients were randomly assigned to receive either placebo (group A, n = 20) or BS capsules (group B, n = 18) for 6 weeks and then switched to the other intervention for another 6 weeks. The disability rating scale (DRS) was used to assess the outcome at 2-, 6- and 12-weeks post-trauma. RESULTS: A non-significant trend for improvement of DRS total scores was observed after the use of BS. Regarding the DRS sub-scores, however, there was significant improvement in 'cognitive ability to self-care' during the second 6 weeks in group A on BS compared to an insignificant spontaneous recovery in group B during the same period on placebo. Moreover, both groups experienced a close-to-significant increase in the cognitive function-related items of the DRS during the periods they were on BS. The reported adverse events were all of mild quality and had similar frequency between the groups. CONCLUSION: These results suggest that BS resin does not significantly affect general outcome, but may enhance the cognitive outcome of patients with DAI.

Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome.

OBJECTIVE: This trial aimed to evaluate the effects of zinc sulfate in comparison with placebo on markers of insulin resistance, oxidative stress, and inflammation in a sample of obese prepubescent children. METHODS: This triple-masked, randomized, placebo-controlled, crossover trial was conducted among 60 obese Iranian children in 2008. Participants were randomly assigned to two groups of equal number; one group received 20 mg of elemental zinc and the other group received placebo on a regular daily basis for 8 weeks. After a 4-week washout period, the groups were crossed over. In addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A-1 (ApoA-I) and B, high-sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde were determined at all four stages of the study. RESULTS: Irrespective of the order of receiving zinc and placebo, in both groups, significant decrease was documented for Apo B/ApoA-I ratio, ox-LDL, leptin and malondialdehyde, total and LDL-cholesterol after receiving zinc without significant change after receiving placebo. In groups, hs-CRP and markers of insulin resistance decreased significantly after receiving zinc, but increased after receiving placebo. In both groups, the mean body mass index (BMI) Z-score remained high, after receiving zinc, the mean weight, BMI, BMI Z-score decreased significantly, whereas these values increased after receiving placebo. CONCLUSION: These results are particularly important in light of the deleterious consequences of childhood obesity and early changes in markers of inflammatory and oxidative stress. We suggest exploring the direct clinical application of zinc supplementation in childhood obesity in future studies.

Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats.

BACKGROUND: Anti-inflammatory drugs with high potency and low systemic adverse effects, such as budesonide, are drugs of choice for the treatment of ulcerative colitis (UC). Budesonide controlled-release formulations are now being used to induce and maintain clinical remission of Crohn's disease. Budesonide-dextran conjugates were synthesized as novel prodrugs of budesonide for oral controlled delivery of the major part of the drug to the colon without needing to coat the pellets of the drug. The aim of this study was to evaluate the in vivo efficacy of this conjugate against acetic acid-induced colitis in rats. MATERIALS AND METHODS: Experimental UC was induced by rectal instillation of 4% solution of acetic acid to rats. After induction of colitis, rats were treated with vehicle (dextran solution), mesalasine (120 mg/kg), budesonide suspension (300 microg/kg) and BSD-70 (equivalent to 300 microg/kg of budesonide), prednisolon (4 mg/kg), hydrocortisone acetate enema (20 mg/kg), and 5-ASA enema (Asacol) (400 mg/kg) for 5 days and then colon macroscopic and microscopic sections were examined for inflammatory response. RESULTS: Vehicle-treated rats presented bloody diarrhoea and gross lesions. The effective formulations for attenuating the damage were BSD-70, oral prednisolon and hydrocortisone acetate enema. Rats treated with BSD-70 showed huge improvement in macroscopic and histological scores of colitis compared to the negative control group and mesalasine and budesonide suspension. CONCLUSION: Data indicated that budesonide-dextran conjugate is effective in improving signs of inflammation in experimental model of colitis through selective delivery of the drug to the inflamed area.

Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome.

BACKGROUND: Since premenstrual syndrome (PMS) can cause suicide, dissociation of familial relationships, abnormalities in the daily work and inter-personal relationships in the patients, and bring about direct and indirect economic burden for the society, it is important to resolve the problems of the patients. The objective of the current study is to determine the effect of magnesium (Mg), combination of vitamin B6 and Mg, and the placebo on the severity of PMS in the patients affected by the disease referred to the health centers of Isfahan University of Medical Sciences during 2009-2010. METHODS: The participants were randomly assigned to two intervention groups and one control group. The study was carried out for four months in ten selected health centers in Isfahan. To confirm the PMS diagnosis in patients, they were asked to fill out the PMS daily symptom record form for two months and then, when the diagnosis was confirmed, the participants were randomly assigned to one of the three groups of the study (Mg, Mg plus vitamin B6, and placebo). Medical intervention was carried out in two menstrual cycles and the results of pre- and post-test were compared. RESULTS: After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group. CONCLUSIONS: The findings indicated that Mg plus vitamin B6 and placebo has the greatest and the least effect on the mean score of PMS, respectively.

Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children.

OBJECTIVE: Zinc, an essential trace element and a component of many enzymes, is involved in the synthesis, storage and release of insulin. The aim of the present study was to assess the effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children. DESIGN: This triple-masked, randomized, placebo-controlled cross-over trial was conducted among 60 obese Iranian children in 2008. Pertinent clinical findings, fasting serum glucose, insulin and lipid profile were assessed. Participants were randomly assigned to two groups of equal number; one group received 20mg elemental zinc and the other group received placebo on a regular daily basis for eight weeks. After a 4-week wash-out period, the groups were crossed over. RESULTS: The mean age of participants was 9.1 +/- 1.1 years. After receiving zinc, the mean fasting plasma glucose (FPG), insulin and HOMA-IR decreased significantly, while body mass index (BMI), waist circumference (WC), LDL-C and triglycerides (TG) did not significantly change. After receiving placebo, the mean FPG, insulin and HOMA-IR increased significantly, while BMI, WC, LDL-C and TG showed a non-significant increase. CONCLUSION: Besides lifestyle modification, zinc supplementation might be considered as a useful and safe additional intervention treatment for improvement of cardiometabolic risk factors related to childhood obesity.

Enhancement of follicular delivery of finasteride by liposomes and niosomes 1. In vitro permeation and in vivo deposition studies using hamster flank and ear models.

Finasteride is indicated orally in the treatment of androgenetic alopecia and some other pilosebaceous unit (PSU) disorders. We wished to investigate whether topical application of finasteride-containing vesicles (liposomes and niosomes) could enhance drug concentration at the PSU, as compared to finasteride hydroalcoholic solution (HA). Liposomes consisted of phospholipid (dimyristoyl phosphatidylcholine (DMPC) or egg lecithin):cholesterol:dicetylphosphate (8:2:1, mole ratio). Niosomes were comprising non-ionic surfactant (polyoxyethylene alkyl ethers (Brij series) or sorbitan monopalmitate):cholesterol:dicetylphosphate (7:3:1, mole ratio). Vesicles were prepared by the film hydration technique and characterized with regard to the size, drug entrapment efficiency and gel-liquid transition temperature (T(c)). In vitro permeation of (3)H-finasteride through hamster flank skin was faster from hydroalcoholic solution (0.13 microg/cm(2)h) compared to vesicles (0.025-0.058 microg/cm(2)h). In vivo deposition of (3)H-finasteride vesicles in hamster ear showed that liquid-state vesicle, i.e. those made of DMPC or Brij97:Brij76 (1:1), were able to deposit 2.1 or 2.3% of the applied dose to the PSU, respectively. This was significantly higher than drug deposition by gel-state vesicles (0.35-0.51%) or HA (0.76%). Both in vitro permeation and in vivo deposition studies, demonstrated the potentials of liquid-state liposomes and niosomes for successful delivery of finasteride to the PSU.