Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking

An estimated 2.5 billion people are at risk of diseases caused by dengue and West Nile virus. As of today, there are neither vaccines to prevent nor drugs to cure the severe infections caused by these viruses. The NS3 protease is one of the most promising targets for drug development against West Nile virus because it is an essential enzyme for viral replication and because success has been demonstrated with the closely related hepatitis C virus protease. We have discovered a small molecule that inhibits the NS3 protease of West Nile virus by computer-aided high-throughput docking, and validated it using three experimental techniques. The inhibitor has potential to be developed to a drug candidate to combat West Nile virus infections

Statistical evaluation of influence of xanthan gum and guar gum blends on dipyridamole release from floating matrix tablets

The present investigation explored the use of xanthan gum and guar gum for development of floating drug delivery system of dipyridamole using factorial design approach. The content of polymer blends (X(1)) and ratio of xanthan gum to guar gum (X(2)) were selected as independent variables. The diffusion exponent (n), release rate constant (k), percentage drug release at 1 hr (Q(1)) and 6 hr (Q(6)) were selected as dependent variables. Tablets of all batches had desired buoyancy characteristics. Multiple regression analysis with two way ANOVA revealed that both the factors had statistically significant influence on the response studied (pPeer reviewe

Intragastric floating drug delivery system of cefuroxime axetil: In vitro evaluation

This investigation describes the development of an intragastric drug-delivery system for cefuroxime axetil. The 32 full factorial design was employed to evaluate contribution of hydroxypropyl methyl cellulose (HPMC) K4M/HPMC K100 LV ratio (polymer blend) and sodium lauryl sulfate (SLS) on drug release from HPMC matrices. Tablets were prepared using direct compression technique. Formulations were evaluated for in vitro buoyancy and drug release study using United States Pharmacopeia (USP) 24 paddletype dissolution apparatus using 0.1N HCl as a dissolution medium. Multiple regression analysis was performed for factorial design batches to evaluate the response. All formulations had floating lag times below 2 minutes and constantly floated on dissolution medium for more than 8 hours. It was found that polymer blend and SLS significantly affect the time required for 50% of drug release, percentage drug release at 12 hours, release rate constant, and diffusion exponent (P<.05). Also linear relationships were obtained between the amount of HPMC K100 LV and diffusion exponent as well as release rate constant. Kinetic treatment to dissolution profiles revealed drug release ranges from anomalous transport to case 1 transport, which was mainly dependent on both the independent variables

Floating granules of ranitidine hydrochloride-gelucire 43/01: Formulation optimization using factorial design

The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 32 full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X1) and ethyl cellulose (X2) as independent variables, and the percentage drug released in 1(Q1), 5(Q5), and 10 (Q10) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f2=62.43). The temperature sensitivity studies for the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl

Insider Trading in Credit Derivatives

Insider trading in the credit derivatives market has become a significant concern for regulators and participants. This paper attempts to quantify the problem. Using news reflected in the stock market as a benchmark for public information, we report evidence of significant incremental information revelation in the credit default swap (CDS) market, consistent with the occurrence of insider trading. We show that the degree of this activity increases with the number of banks that have lending/monitoring relations with a given firm, and that this effect is robust to controls for noninformational trade. Furthermore, consistent with hedging activity by informed banks with loan exposure, information revelation in the CDS market is asymmetric, consisting exclusively of bad news. We find no evidence, however, that the degree of insider activity adversely affects prices or liquidity in either the equity or credit markets. If anything, with regard to liquidity, the reverse appears to be true