An approach to determine crystalline content of Granisetron in transdermal patches using X-ray diffraction technique

Granisetron is a drug used to treat nausea and vomiting after chemotherapy. Crystallization of drug is always a major concern in the transdermal drug delivery system. In view of consistent biopharmaceutical performance, monitoring and controlling the crystallization during product development and shelf life is very important. The need was felt to have an accurate method for determination of crystallinity in transdermal patches.The present study is about development and validation of a quantitative X-ray diffraction method for the determination of the extent of crystallization of the drug in transdermal formulation of Granisetron. Specimens of different physically spiked concentrations were carefully prepared accurately by weighing and distributing crystalline active pharmaceutical ingredient (API) onto placebo liner patches, pasted on Silicon low background sample holder (diameter of 24.5 mm, made up of Si crystal). All the specimens thus prepared were scanned using optimized instrumental parameters while enabling specimen rotation during the diffraction analysis to ensure homogeneous exposure to the incident X-rays. Using this novel approach, limit of detection

Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study

BACKGROUND & AIMS: The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. METHODS: In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. RESULTS: Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P 365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. CONCLUSIONS: Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality

General method for prediction of thermal conductivity for well-characterized hydrocarbon mixtures and fuels up to extreme conditions using entropy scaling

A general and efficient technique is developed to predict the thermal conductivity of well-characterized hydrocarbon mixtures, rocket propellant (RP) fuels, and jet fuels up to high temperatures and high pressures (HTHP). The technique is based upon entropy scaling using the group contribution method coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state. The mixture number averaged molecular weight and hydrogen to carbon ratio are used to define a single pseudo-component to represent the compounds in a well-characterized hydrocarbon mixture or fuel. With these two input parameters, thermal conductivity predictions are less accurate when the mixture contains significant amounts of iso-alkanes, but the predictions improve when a single thermal conductivity data point at a reference condition is used to fit one model parameter. For eleven binary mixtures and three ternary mixtures at conditions from 288 to 360 K and up to 4,500 bar, thermal conductivities are predicted with mean absolute percent deviations (MAPDs) of 16.0 and 3.0% using the two-parameter and three-parameter models, respectively. Thermal conductivities are predicted for three RP fuels and three jet fuels at conditions from 293 to 598 K and up to 700 bar with MAPDs of 14.3 and 2.0% using the two-parameter and three-parameter models, respectively

FHA-Mediated Cell-Substrate and Cell-Cell Adhesions Are Critical for Bordetella pertussis Biofilm Formation on Abiotic Surfaces and in the Mouse Nose and the Trachea

Bordetella spp. form biofilms in the mouse nasopharynx, thereby providing a potential mechanism for establishing chronic infections in humans and animals. Filamentous hemagglutinin (FHA) is a major virulence factor of B. pertussis, the causative agent of the highly transmissible and infectious disease, pertussis. In this study, we dissected the role of FHA in the distinct biofilm developmental stages of B. pertussis on abiotic substrates and in the respiratory tract by employing a murine model of respiratory biofilms. Our results show that the lack of FHA reduced attachment and decreased accumulation of biofilm biomass on artificial surfaces. FHA contributes to biofilm development by promoting the formation of microcolonies. Absence of FHA from B. pertussis or antibody-mediated blockade of surface-associated FHA impaired the attachment of bacteria to the biofilm community. Exogenous addition of FHA resulted in a dose-dependent inhibitory effect on bacterial association with the biofilms. Furthermore, we show that FHA is important for the structural integrity of biofilms formed on the mouse nose and trachea. Together, these results strongly support the hypothesis that FHA promotes the formation and maintenance of biofilms by mediating cell-substrate and inter-bacterial adhesions. These discoveries highlight FHA as a key factor in establishing structured biofilm communities in the respiratory tract

Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study

The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study

Design and characterization of delavirdine ethosomal drug delivery to enhance the bioavailability via topical drug delivery

The increasing demand for efficient administration and delivery of pharmaceutical dosage forms possessing the attributes namely minimum side effects, improved patient compliance has resulted in the formulation of novel drug delivery system. Ethosomes are very effective since they enhance the penetration of drugs via skin to several times whose compound to the simple creams, elixirs and liposomal carriers. Hence, there is an absolute necessity to formulate ethosomes of the selected drugs, In the presant work ethosomal formulations of, delaviridine, was prepared for obtaining the objective of improving skin permeability and bioavailability. The prepared formulations gave good percentage yield and size distribution. The best formulation of ethosomes of each respected drug were incorporated into carbopol based gel systems for controlled release and the invitro studies proven that the formulations followed zero order release mechanisms. Compatability studies were performed for the materials selected and results are observed o be possitive. Stability studies indicated that the formulations were stable at low temperatures but can undergo rapid deformation at higher temperatures

Performance of 4- and 8-State TCM Schemes with Asymmetric 8-PSK in Fading Channels

For Rayleigh fading channels, Ricean fading channels with a small parameter and shadowed Rician channels with the code design criteria are to maximize the effective length as well as the minimum product distance of the code. In this paper, we use two different asymmetric 8-PSK signal sets in 4-state and I- state rate 2/3 trellis-coded modulation (TCM) schemes and show performance gain over TCM schemes with symmetric 8-PSK constellations. The performance gain is due to an increase in the minimum product distance compared to that of the best known TCM schemes of comparable states using symmetric 8-PSK signal sets while the effective length remains same. Simulation is performed over the Rayleigh, Ricean, and shadowed Rician fading channels to demonstrate the performance gain of the asymmetric 8-PSK TCM schemes over the symmetric 8-PSK TCM

Performance of 4- and 8-State TCM Schemes with Asymmetric 8-PSK in Fading Channels

For Rayleigh fading channels, Ricean fading channels with a small parameter and shadowed Rician channels with the code design criteria are to maximize the effective length as well as the minimum product distance of the code. In this paper, we use two different asymmetric 8-PSK signal sets in 4-state and I- state rate 2/3 trellis-coded modulation (TCM) schemes and show performance gain over TCM schemes with symmetric 8-PSK constellations. The performance gain is due to an increase in the minimum product distance compared to that of the best known TCM schemes of comparable states using symmetric 8-PSK signal sets while the effective length remains same. Simulation is performed over the Rayleigh, Ricean, and shadowed Rician fading channels to demonstrate the performance gain of the asymmetric 8-PSK TCM schemes over the symmetric 8-PSK TCM