Design and development of microemulsion drug delivery system of atorvastatin and study its intestinal permeability in rats

The objective of this study was to design and develop microemulsion drug delivery system of Atorvastatin and to investigate its intestinal transport behavior using the single-pass intestinal perfusion method in rat. Microemulsion drug delivery system of Atorvastatin was prepared by water titration method and optimized formulation was characterized. The permeability behavior of Atorvastatin over three different concentrations (10, 20 and 40 μg/mL) was studied in each isolated region of intestine (i.e. duodenum, jejunum, ileum and colon) of rat by single-pass intestinal perfusion method in rat method at a flow rate of 0.2 ml/min. The concentration of the sample was determined by HPLC and the effective permeability coefficients were calculated. Considering the high correlation of rat permeability coefficient values with those of human, the human intestinal permeability was predicted using the Lawrence compartment absorption and transit model. The intestinal permeability of Atorvastatin in microemulsion, plain drug suspension and marketed formulation was also compared. The particle size and zeta potential of Atorvastatin microemulsion were (18.2±0.3) nm and (–9.19±0.8) mV respectively. There was no significant difference in permeability coefficient in jejunum, duodenum and ileum with same concentration but higher in colon was observed. The permeability coefficient in jejunum at 10 μg/mL was significantly higher than that at 40 μg/mL (p< 0.01). The estimated human intestinal permeability of Atorvastatin for the microemulsion was relatively higher. Based on the above results, it could be concluded that microemulsion formulation could enhance the intestinal permeability of Atorvastatin and thus could be presented as a possible alternative to traditional oral formulations for improving the oral absorption of Atorvastatin.Keywords: Microemulsion;, Zeta potential; Atorvastatin; Single-pass intestinal perfusion (SPIP) method; Compartment absorption and transit model (CAT

Quantum version of transport coefficients in Nambu--Jona-Lasinio model at finite temperature and strong magnetic field

We have estimated parallel and perpendicular components of electrical conductivity and shear viscosity of quark matter at finite magnetic field and temperature by using their one-loop Kubo expressions in the framework of Nambu--Jona-Lasinio (NJL) model. At finite magnetic field, a non-trivial medium dependence of those quantities can be found. Previously these NJL-profiles have been addressed in relaxation time approximation, where cyclotron motion of quarks with medium dependent mass plays the key role. With respect to the earlier estimations, the present work provides further enriched profiles via Kubo framework, where field theoretical descriptions of quark transport with medium dependent mass and (Landau) quantized energy have been identified as the key ingredients. Hence the present study can be considered as the complete quantum field theoretical description of the transport coefficients in the framework of NJL model at finite temperature and magnetic field.Comment: 16 pages, 2 figure

Chemical Enrichment at High Redshifts

We have tried to understand the recent observations related to metallicity in Ly $\alpha$ forest clouds in the framework of the two component model suggested by Chiba & Nath (1997). We find that even if the mini-halos were chemically enriched by an earlier generation of stars, to have [C/H] $\simeq$ -2.5, the number of C IV lines with column density $>10^{12} cm^{-2}$, contributed by the mini-halos, at the redshift of 3, would be only about 10% of the total number of lines, for a chemical enrichment rate of $(1+z)^{-3}$ in the galaxies. Recently reported absence of heavy element lines associated with most of the Ly $\alpha$ lines with H I column density between $10^{13.5} cm^{-2}$ and $10^{14} cm^{-2}$ by Lu et al (1998), if correct, gives an upper limit on [C/H]=-3.7, not only in the mini-halos, but also in the outer parts of galactic halos. This is consistent with the results of numerical simulations, according to which, the chemical elements associated with the Ly $\alpha$ clouds are formed in situ in clouds, rather than in an earlier generation of stars. However, the mean value of $7 \times 10^{-3}$ for the column density ratio of C IV and H I, determined by Cowie and Songaila (1998) for low Lyman alpha optical depths, implies an abundance of [C/H] =-2.5 in mini-halos as well as in most of the region in galactic halos, presumably enriched by an earlier generation of stars. The redshift and column density distribution of C IV has been shown to be in reasonable agreement with the observations.Comment: 23 pages, 6 figures, To appear in Astrophysical Journa

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: a preliminary investigation

yesRationale: Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Methods: Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for seven days, followed by seven days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Results: Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial (P<0.01). scPCP produced a significant deficit in NOR (P<0.05 vs. control) and no PFC dopamine increase was observed. Conclusions: These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology

Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors

Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer’s disease. A structure–activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved

Development of cucurbocitrin based nutraceutical formulation: A potential adjuvant herbal therapy in the management of hypertension

Nearly half of the hypertensive patients fail to manage their blood pressure despite pharmacological interventions, which reflects the dire need for adjuvant anti-hypertensive therapies. Nutraceutical formulations are attractive in this regard owing to their efficacy, ease of availability, and moderate pricing. The current investigation involves the formulation of cucurbocitrin nutraceutical tablets by direct compression method and evaluated for its anti-hypertensive effect in the management of hypertension. Cucurbocitrin is a natural compound prepared from Citrullus lanatus seeds belonging to the family Cucurbitaceae. The powder blend was examined for pre-compression studies such as angle of repose, bulk density, tapped density, Carr’s index, Hausner's ratio, etc. Based on acute-oral toxicity results, two tablet formulations were prepared using a different dose of cucurbocitrin and evaluated for post-compression parameters such as friability, hardness, weight variation, disintegration time, and in vitro drug release studies. In vivo studies were also performed for both formulations using a 10% Glucose solution-induced hypertension model in albino rats to observe its anti-hypertensive activity. The study indicated that nutraceutical formulation was found to be effective in reducing hypertension in an animal model