Pharmaceutical Sciences
Volume:16 Issue: 1, 2010

The purpose of this study was to prepare and evaluate carbamazepine (CBZ) superdisintegrants agglomerates by spherical crystallization technique. The process involved recrystallization of CBZ and its simultaneous agglomeration with disintegrants: sodium starch glycolate (SSG) or croscarmellose sodium (CCS). An ethanol, isopropyl acetate, water system was used, where they acted as solvent, bridging liquid and non-solvent respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), FTIR and Scanning electron microscopy and were evaluated for micromeritic properties, disintegration time and drug release. In comparison to conventional drug crystals, the agglomerates depicted significantly improved micromeritic properties and their dissolution rates were enhanced. Although CBZ-CCS agglomerates showed better disintegration time than CBZ-SSG agglomerates, CCS had lower effect on dissolution rate, probably due to possible charge interactions with drug. Spherical crystallization is an efficient and simple technique, which is useful for preparing drug-superdisintegrants agglomerates to improve the micromeritic properties and the dissolution rates.

This study initiated to evaluate the pathologic changes of pancreas, liver and kidney in diabetes rats treated with T. polium. In an experimental study, the crude extract of T. polium was administered orally to a group of streptozotocin (STZ) diabetic rats for 6 consecutive weeks. The control healthy rats and the control diabetic rats received distilled water. Tissue samples were routinely processed and stained with H&E and PAS. Significant decrease in blood glucose, increase in serum alkaline phosphatase and insulin secretion were observed in treated diabetic rats. Histopathologic study of diabetic rats revealed reduction in the number of pancreatic islets as well as their number of β-cells and insulitis (inflammation of pancreatic islets) with lymphocytes infiltration. Regeneration of pancreatic islets and β-cells, along with a reduction in the number of infiltrated lymphocytes, hepatitis with hypertrophy and hyperplasia of Kupffer's cells and infiltration and sequestration of polymorphonuclears and tubulointerstitial nephritis with focal necrosis were present in plant extract-treated diabetic rats. The plant extract seems to be capable of regenerating the islets of langerhans in the treated rats compared to the untreated diabetic rats. Severe changes due to the plant extract in organs such as liver and kidney could explain increase of alkaline phosphatase activity. Further works are required to explore exactly the mechanisms of islet regeneration by the plant extract its side effects.

Many evidence indicated that glucocorticoids have modulatory effects on pain and probably one of the mechanism that mediate of these effects is nitric oxide system. The aim of this study was determine of interaction between corticosterone and Nitric oxide (NO) system on acute (Neurogenic) and chronic (Inflammatory) pains in Formalin Test (FT) model in mice. In this experimental study we used 70 male albino mice (25-30 g) in 7 groups. Also we used of FT for evaluation of acute and chronic pain. The criteria for evaluation of pain was measure of all time that animal reaction to pain responses (Licking Time) after injection of formalin 5%) in sub-plantar area of the right hind paw in each of 5 min, during 40 min. All animals received two IP injection, L-Name (10 mg/kg) as a NO synthesis inhibitor or L-arginine (20 mg/kg), as a NO precursor, 60 min and different doses of corticosterone (1and 3 mg/kg) or Vehicle (Propylene glycol 40% + Saline in 6 ml/kg) were injected 30 min before of FT. Analysis of data indicated that corticosterone at doses of 1 and 3 mg significantly reduced pain reaction in mice. Also pretreatment of L-Name enhanced the analgesic effects of corticosterone in chronic pain, while injection of Larginine, as a NO precursor had not significantly effects. The findings indicated that glucocorticoids induce analgesic effects probably through of modulation of NO system.

Atropine is a pharmaceutical important alkaloid, with anticholinergic activity. Elicitor treatment appears to be the most successful techniques employed to stimulate biosynthesis of secondary metabolites. In present study callus culture of Datura metel were treated with salicylic acid in order to stimulate the biosynthesis of atropine. Callus culture of Datura metel were established by transferring seedling on solidified MS medium. Optimal callus of fifth generation were subjected to medium supplemented with different concentration of salicylic acid. After twenty eight days calluses were collected, dried and extracted. The atropine was determined using HPLC method. Treatment of the culture with 25, 50, 200 μM salicylic acid increased callus dried weight. No significant differences were observed in atropine production in callus treated with 25, 50, 200 μM salicylic acid. It seems that salicylic acid in specific concentration can stimulate primary metabolism in callus culture of Datura metel but no changes was observed in secondary metabolism related to atropine production. It may conclude that salicylic acid effect on secondary metabolite production in plant cell culture related to the moiety of target compound and plant genetics.

Ornithogalum cuspidatum Bertol is an Iranian species of the genus Ornithogalum L. (family: Liliaceae). In the Iran, the aerial parts of O. cuspidatum are used as food additives and also as an anti-irritant and relaxant by soothing the throat and bronchial tubes during dry coughs. Only limited phytochemical investigation has yet been carried out on O. caspidatum. The essential oils were obtained by hydrodistillation in a clevenger extractor and the composition of essential oils of flowers, leaves and bulbs were determined by coupled GC-MS analysis. The yields of essential oils of fresh flowers, leaves and bulbs were 0.016%, 0.007% and 0.037% respectively. The GC-MS analysis of the essential oils of bulbs, flower and leaves led to the identification and quantification of a total of 155, 20 and 23 compounds respectively. The major components of flower’s oil were hexacosane (31.49%), ethyl linoleolate (2.74%), tricosane (7.72%), tetracosane (3.46%), heptacosane (5.65%), Octacosane (25.22%) and tetracosane,11-decyl- (10.03%); and about leave’s oil were Hexahydro farnesyl acetone (5.71%), Palmitic acid (16.01%), tricosane (17.42%), linolenic acid methyl ester (9.01%), heneicosane (5.30%) and phytol (20.71%). Also the major components of bulb’s oil were nonane (2.65 %), 4-methyl nonane (2.76%), decane (9.65 %) and undecane (7.73 %). Analysis of the essential oil of different parts of O. cuspidatum showed that the essential oils of flower and bulb consisted mainly of saturated hydrocarbon compounds. Although, the essential oil of the leaves consisted mainly of from oxygenated hydrocarbons. Also, the essential oil of the flower contained oxygenated terpenoid compounds (4.84%).

Parkinson is a neurodegenerative disease characterized by damage of striatal dopaminergic neurons. Recently it has been reported that other neurotransmitter systems, such as serotonergic neurons are involved in pathogenesis of Parkinson disease. Thus, we investigated the effect of fluoxetine, as a specific serotonin reuptake inhibitor, on motor disorders induced by unilateral infusion of 6-OH-dopamine into the substantia nigra, compact part (SNc). Study was carried out on male Wistar rats weighing between 180-200 g. In oredr to induce experimental model of Parkinson disease, 6-hydoxydopamine (6- OHDA, 8 μg/rat) was injected unilaterally into the SNc. 6-OHDA-induced catalepsy and balance disturbances were assessed respectively by using bar test and rotarod 5, 60, 120 and 180 minutes after intraperitoneal (i.p.) injections of the drugs. 6-OHDA (8 μg/rat, Intra-SNc) induced noticeable (P<0.01, 0.001) motor disorders of Parkinson disease. Fluoxetine alone (0.1, 0.5 and 1 mg/kg, i.p.) did not produced significant effect (P>0.05) in bar test and rotarod. Whereas, fluoxetine (0.1, 0.5 and 1 mg/kg, i.p.) attenuated (P<0.01, 0.001) and increased (P<0.05, 0.01) 6-OHDA induced catalepsy and motor disturbances respectively. In 6-OHDA-lesioned rats, the effect of fluoxetine (0.5 mg/kg, i.p.) on catalepsy and balance disturbances was reversed (P<0.01, 0.001) by NAN-190 (0.5 mg/kg, i.p.). Fluoxetine reduces -OHDA-induced catalepsy by affecting on 5-HT1A receptors. Adjuvant therapy with fluoxetine and antiparkinsonian drugs may produce better control in Parkinson disease symptoms.

The delivery of protein pharmaceuticals to the systemic circulation through oral administration is the goal of many research groups. This route of administration is hindered by numerous barriers. New drug delivery systems such as vesicles can overcome this barriers. Different niosomal formulations composed of sorbitan monoesters (Spans®)/ polyoxyethylen sorbitan esters (Tweens®)/cholesterol were prepared for encapsulation of insulin with or without aprotinin. In vitro characterization of vesicles were carried out including size distribution analysis, microscopic observation, insulin release measurement and SDS-gel electerophoresis.The protection of protein against three enzymes was evaluated. Span/Tween 80 did not form niosomes, but the other surfactant combinations formed stable niosomal suspensions. Insulin was protected from proteolytic effects of enzymes efficiently (p<0.05). the mean volum diameter of prepared lipid vesicles was related directly to hydrophilicity of surfactants indicated by hydrophilicic-lipophilic balance (HLB) of the used amphiphiles. The maximum encapsulation of insulin 48.9±13.08, was seen in Span/Tween 60 formulations. The release profile of insulin was tow-phasic in both simulated gastric and intestinal fluids. Aprotinin had no significant effect on the protection of insulin (p<0.05). these results indicated that niosomes could be developed as oral dosage forms for delivery of proteins such as insulin.