Synthesis, Characterization and Biocompatibility Evaluation of Novel Chitosan Lipid Micro-Systems for Modified Release of Diclofenac Sodium.

The purpose of our study was the obtaining, characterization and biocompatibility estimation of novel carrier systems for diclofenac. Diclofenac is a potent nonsteroidal anti-inflammatory drug with frequent gastrointestinal side effects, impairing the quality of the patient's life. Original diclofenac-loaded micro-vesicles coated with chitosan were prepared and physico-chemical analyzed. We investigated their in vitro hemocompatibility and in vivo biocompatibility in rats. The animals were treated orally as follows: group 1 (Control): distilled water 0.3 mL/100 g body weight; Group 2 (CHIT): 0.3 mL/100 g body weight 0.5% chitosan solution; Group 3 (DCF): 15 mg/kg body weight diclofenac; Group 4 (DCF-ves): lipid vesicles loaded with diclofenac 15 mg/kg body weight. Blood samples were collected for assessing: red blood cells, hemoglobin, hematocrit and leukocyte formula. A series of specific parameters of the liver and kidney function, some markers of immune defense, as well as the activity of some enzymes involved in oxidative processes, were also investigated. At the end of the experiment, the animals were sacrificed and fragments of liver, kidney and stomach were collected for histopathological examination. No blood hemolysis was evidenced by the in vitro test with the administration of diclofenac vesicles. The animals treated with diclofenac lipid vesicles stabilized with chitosan did not display any notable differences in their hematological and biochemical profile compared to control animals. These data correlated with the histological results, which showed the absence of architectural changes in the examined tissues. Biological in vitro and in vivo evaluation revealed that the microvesicles containing diclofenac are biocompatible, with potential to be used as delivery systems to modify the drug release, thus making them an attractive candidate for biomedical applications.

Magnesium Potentiates the Vortioxetine's Effects on Physical Performances and Biological Changes in Exercise-Induced Stress in Rats.

Background and objectives: Vortioxetine (VRT) is a relatively new selective serotonin reuptake inhibitor (SSRI) antidepressant and serotonin receptor modulator, approved for the treatment of major depression and generalized anxiety disorder. Depression has been linked with psychomotor disengagement, oxidative stress burden and decreased blood levels of brain-derived neurotrophic factor (BDNF). In our study we performed the experimental investigation of VRT, magnesium and of their association on the rats' endurance capacity, motor behavior and blood biological disturbances in rats subjected to forced exercise in treadmill test. Materials and Methods: The substances were administered orally for 14 consecutive days, as follows: group 1 (control): distilled water 0.3 mL/100 g body; group 2 (Mg): magnesium chloride 200 mg/kg body; group 3 (VRT): VRT 20 mg/kg body; group 4 (VRT+Mg): VRT 20 mg/kg body + magnesium chloride 200 mg/kg body. Magnesium was used as positive control substance with known effects in treadmill test. The consequences of VRT treatment on glucose, cortisol, BDNF and oxidative stress biomarkers (superoxide-dismutase, malondialdehyde, glutathione-peroxidase, lactate dehydrogenase) were also assessed. Results and conclusions: The use of VRT resulted in an improvement in motor capacity and an increase of the rats' endurance to physical effort. The administration of VRT increased the serum BDNF levels and reduced the oxidative stress in rats subjected to physical effort. The association of magnesium potentiated the effects of VRT on physical performances, the antioxidant activity and the decreasing in serum stress markers in treadmill test in rats.

Assessment of the In Vivo Release and Biocompatibility of Novel Vesicles Containing Zinc in Rats.

This paper is focused on the in vivo release and biocompatibility evaluation in rats of some novel systems entrapping zinc chloride in lipid vesicles. The particles were prepared by zinc chloride immobilization inside lipid vesicles made using phosphatidylcholine, stabilized with 0.5% chitosan solution, and dialyzed for 10 h to achieve a neutral pH. The submicrometric systems were physico-chemically characterized. White Wistar rats, assigned into four groups of six animals each, were treated orally with a single dose, as follows: Group I (control): deionized water 0.3 mL/100 g body weight; Group II (Zn): 2 mg/kg body weight (kbw) zinc chloride; Group III (LV-Zn): 2 mg/kbw zinc chloride in vesicles; Group IV (LVC-Zn): 2 mg/kbw zinc chloride in vesicles stabilized with chitosan. Haematological, biochemical, and immune parameters were assessed after 24 h and 7 days, and then liver fragments were collected for histopathological examination. The use of zinc submicrometric particles-especially those stabilized with chitosan-showed a delayed zinc release in rats. No substantial changes to blood parameters, plasma biochemical tests, serum complement activity, or peripheral neutrophils phagocytic capacity were noted; moreover, the tested substances did not induce liver architectural disturbances. The obtained systems provided a delayed release of zinc, and showed good biocompatibility in rats.

The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination.

OBJECTIVES: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations. METHODS: The oral tablets were made by using a Christ freeze-dryer alpha 2-4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams. RESULTS: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets. CONCLUSION: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the 'codrug' complex, which do not affect the release of the bioactive compounds.

New Nitric Oxide Donors With Therapeutic Potential.

Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.

Imidazoline receptor antagonists idazoxan and efaroxan enhance locomotor functions in rats.

UNLABELLED: Discovered in 1984, imidazoline receptors (I1, I2, I3) are located centrally and peripherally being involved in various physiologic and pathophysiologic processes in the body. Experimental and clinical investigations have suggested the interrelations between imidazoline, adrenergic, dopaminergic, glutamatergic and opioid systems, which may explain the influence of different substances acting on imidazoline receptors in cognitive disorders, behavioral disturbances and motor diseases pathways. AIM: To investigate the effects of two imidazoline receptor antagonists on locomotor activity and endurance capacity in rats. MATERIAL AND METHODS: The experiment was carried out with white male Wistar rats (200-250 g) divided into 3 groups of 7 animals each, treated intraperitonealy with the same volume of solution as follows: Group I (Control): distilled water 0.3 ml/100 g body weight; Group II (IDZ): idazoxan 3 mg/kbw; Group III (EFR): efaroxan 1 mg/kbw. Exercise capacity was evaluated using a locomotor PanLAB treadmill test. The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. Experimental protocol was implemented according to recommendations of the Gr.T. Popa" University Committee for Research and Ethical Issues. RESULTS: Intraperitoneal administration of idazoxan and efarox- an resulted in a significant increase in running distance compared with the control group (p < 0.05). At the same time a reduction in the number and time of electric shocks delivered to motivate the animal to keep running was observed. In this experimental behavioral model the effects of idazoxan on the evaluated parameters were more intense than those of efaroxan. CONCLUSIONS: In our experimental conditions we demonstrated the ability of imidazoline receptor antagonists idazoxan and efaroxan to improve fatigue resistance during forced running in rats.

Effects of some dopamine antagonists on spatial memory performance in rats--experimental research.

UNLABELLED: Dopamine is a neurotransmitter with an important role in forming long-lasting memories for some time, especially in episodic memory. Literature data show that dopamine receptor stimulation may be detrimental to spatial working memory functions in lab animals. (R)-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride derivative--SCH-23390 is a synthetic compound that acts as a selective, high-affinity antagonist of D1 receptors. Experimental studies suggest that SCH 23390 may prevent the spatial working memory disturbances induced by the active substances of marijuana. Melperone is an atypic antipsychotic drug presenting also dopaminergic D2 and 5-HT2A receptor antagonistic activity. This neuroleptic agent is used in the treatment of some types of schizophrenia. AIM: Experimental research on the effects of two dopamine receptor antagonists on spatial memory performance in rats. MATERIAL AND METHODS: The experiment was carried out in white Wistar rats (200-250g), divided into 3 groups of 7 animals each, treated intraperitoneally with the same volume of solution for 14 days, as follows: Group I (Control): saline solution 0.1 ml/10g kbw; Group II (coded SCH): SCH-23390 0.3 mg/kbw; Group III (coded MLP): melperone 2 mg/kbw. The dopaminergic agent spatial memory performance was assessed by recording spontaneous alternation behavior in a single session in Y-maze. Each animal was placed at the end of one arm and allowed to move freely through the maze during an 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed with the following formula: number of alternations divided by total number of arm visits minus 2. Data were presented as +/- standard deviation and significance was tested by SPSS Statistics for Windows version 13.0 and ANOVA method. P-values less than 0.05 were considered statistically significant compared to those in the control group. Experimental researches were carried out in compliance with the regulations of our University Committee for Research and Ethical Issues. RESULTS: SCH-23390 (0.3 mg/kbw) and melperone (2 mg/kbw) intraperitoneal injection for 14 days determined a statistically significant (p < 0.05 and p < 0.01, respectively) increase in spontaneous alternation rate (compared to controls in Y-maze test). CONCLUSIONS: Our research revealed that the 14 consecutive days administration of these two dopamine receptor antagonists was associated with the improvement of short-term memory in rats, more intense for SCH-23390 compound.

Visible spectrophotometric method for amiodarone.

Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmia, both ventricular and supraventricular (atrial) arrhythmia. A spectrophotometric method for the assay of amiodarone was established. Based on the reduction of potassium ferricyanide in hydrochloric acid medium to potassium ferrocyanide forming a blue colored complex ferric ferrocyanide with Fe (III) ions. The compound was most stable in a mixture of ethylic alcohol and water (2:1, v/v) and it had an absorption maximum at 725 nm. The data were according to the Lambert-Beer Law in the concentration range of 0.5-5.0 microg/sample: correlation and coefficient R = 0.99977, R2 = 0.999541, slope of the line 0.12775, intercept 0.042077. The detection limit (DL) was 0.1032 microg/sample and the quantification limit (QL) 0.344 microg/ sample.

Zinc--essential micronutrient for child health and nutrition.

Ubicuity of zinc in nature has generally lead to the idea that human zinc deficiency is hardly to appear; however, the last 40 years of research studies showed clear correlation between zinc deficiency and several clinic manifestations: growth retardation, predisposal to infections, delay of wound healing, hypogonadism in boys. Zinc plays multiple roles, especially in pregnant women and children. Although the issue of micronutrient malnutrition has been pointed out in developing countries, it has been remarked also in developed ones, due to unbalanced nutrition and diets. The article aims pointing out important aspects related to zinc micronutrient: metabolic pathway, daily dosage, health benefits as prophylaxis and therapy of respiratory and digestive infections in children.

[Oral disintegrating tablets. A new, modern, solid dosage form]. / Comprimatele orodispersabile forma farmaceutica moderna.

The pharmaceutical market shows lately an increasing interest in orally disintegrating tablets, due to their good acceptability among certain age categories (ex. elderly, children), and other patients with difficulties in swallowing classic solid dosage forms. Some of the methods of preparing such tablets have gained industrial applicability: molding, lyophilization, direct compression with highly soluble excipients, super disintegrants and/or effervescent systems. Some of the patients have had a good impact on the pharmaceutical market and more improvements are expected in the next few years, with new drugs to be formulated as fast dissolving dosage formulations.