SOLUBILITY ENHANCEMENT OF KETOCONAZOLE VIA SALT AND COCRYSTAL FORMATION

Objective: Pharmaceutical salt and cocrystal is a promising alternative method for improving the solubility and dissolution rate of active pharmaceutical ingredients. In this work, an attempt was made to improve solubility of ketoconazole (KTZ) using salt formation and cocrystallization technique.Methods: Salt and cocrystal were prepared using oxalic acid (OXA) and fumaric acid (FUMA) via slurry conversion method. Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) techniques were employed to investigate the crystallinity, melting point and morphology of salt and cocrystal respectively. KTZ salt and cocrystal were evaluated further for their solubility, stability and antifungal activities.Results: Synthesis of KTZ OXA salt and KTZ FUMA cocrystal were successfully carried out using slurry conversion method using ethyl acetate solvent. The result from PXRD, DSC and SEM analysis confirms the formation of salt and cocrystal of KTZ with OXA and FUMA. Saturation solubility studies in water at 25 °C exhibited a remarkable improvement in the drug solubility. KTZ FUMA and KTZ OXA were considered to be stable over the period of 1 month confirmed by the stability study. In vitro antifungal activity study revealed that the formation of KTZ OXA and KTZ FUMA did not alter the therapeutic activity as an antifungal agent.Conclusion: Salt and cocrystal of KTZ (KTZ OXA and KTZ FUMA) exhibit enhanced solubility compare the pure drug. In vitro antifungal study revealed that both salt and cocrystal of KTZ retained their antifungal activities

Supplement III:31

GCCX cont. : Getsu Fuma De

A Procedure for Characterizing Tactile Sensors

We describe a methodology for the characterization of tactile sensors. We address the questions of verification of manufacturer\u27s claims about the output of a sensor, reliability of the output and robustness of the sensor over time. In our work with tactile sensors, it has become apparent that there is a need for a rigorous methodology of characterizing sensor quality. We implement this as a procedure which is specific for the Lord LTS-200 sensor [ref 1] With some modifications, this methodology could be applied to other tactile sensors

A Real-Time Display for Tactile Images

The tactile array sensor is a key component of the multi-sensory integration work at the General Robotics and Active Sensory Perception Laboratory (GRASP Lab) at the University of Pennsylvania. In our work, tactile sensors provide information about the nature of the contact between an actuated tool, such as a robotic gripper, and its physical domain. This information is used for feedback control of the gripper and robot manipulator to which it is attached, and for tactile perception. The sensor we currently use, LTS-200 from Lord Corp. [r@. I], consists of a two separate modules (see figure 1): • a 10 x 16 tactile array, which measures displacement (or deflection) via optical technology. • a 6 degree of freedom force/torque module using strain gauge technology. The force/ torque module is mounted under the tactile array. This is not an array, its output is scalar. The interface and signal processing circuitry is located in an external box. The data obtained from the LTS-200 tactile array describes the amount of deformation of the sensor cover. The sensor cover, made from a synthetic rubber, can deform, up to a point, to comply with the surface of the object under investigation (see figure 2). The sensing array samples this surface and data is obtained describing the texture and local shape of the contact area. This tactile sensor can be compared to a range finder, but with very limited span. The second module of the LTS-200 provides overall force, in x, y and z direction, and overall moments, around the x, y and z direction, which result from pressing the sensor against an object. In the course of using the LTS-200, or evaluating new sensors, we felt a need for visualizing the tactile information obtained. We looked for a format that provides insight into the tactile image and is suitable for further post-processing

Genome-wide association studies of the self-rating of effects of ethanol (SRE).

The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging