Improved oral bioavailability of poorly water soluble drugs using rapid freezing processes

textA growing number of therapeutic compounds currently being developed by pharmaceutical companies are poorly water soluble leading to limited and/or erratic bioavailability. The rate limiting step for absorption of these compounds is dependent on the dissolution and apparent solubility. Nanoparticle formation has been exploited as a method to improve the bioavailability of these poorly water soluble active pharmaceutical ingredients (API) by increasing the dissolution rates and apparent solubilities. The influence of hydrophilic stabilizers in powder compositions prepared by the spray freezing into liquid (SFL) process using either an emulsion feed dispersion or organic co-solvent feed solutions on enhancing the wetting and dissolution properties of nanostructured aggregates containing itraconazole (ITZ). Subsequently, an in vivo pharmacokinetic study was conducted comparing the SFL processed powder to commercial Sporanox®. An ultra-rapid freezing (URF) technology has been developed to produce high surface area powders composed of solid solutions of an active pharmaceutical ingredient (API) and a polymer stabilizer. Rapid freezing technologies are known to enhance the physico-chemical properties of APIs and thus increase bioavailability. However, the effect of the different freezing geometries and rates in the URF process are unknown. Therefore, this study investigated how solvent properties and thin film geometry of the droplet affect the freezing rate and thus the physico-chemical properties of micronized danazol powders. Amorphous nanoparticles containing tacrolimus (TAC) in a solid dispersion were prepared using the Ultra-rapid Freezing (URF) process. The objective of this study was to assess the effects of combinations of polymeric stabilizers on the maximum degree and extent of supersaturation of TAC. An attempt to establish if an in vitro-in vivo correlation exists between supersaturation and improved pharmacokinetic parameters for orally dosed TAC was performed. Enteric solid dispersions could overcome limitations of premature precipitation of supersaturated solutions by 1.) delaying dissolution until the compound enters the intestines where absorption is favored and 2.) increasing the apparent solubility at higher pH to increase the driving force for absorption. The objective of the study is to investigate the influence of composition parameters including drug:polymer ratio and polymer type, and particle structure of enteric solid dispersions on the release of ITZ.Pharmac

PEER GROUP INFLUENCES UPON ADOLESCENT DRINKING PRACTICES

Utilizing longitudinal data on 345 high school students, this study investigates the impact that peer identification, sociability, activity, and perceptions of peer attitudes governing the use of alcohol have upon adolescent alcohol use, and the likelihood of experiencing personal problems as a consequence of drinking. The major findings are that adolescent orientations toward alcohol are responsive to all but peer identification, and that the predictors generally exert their strongest influences upon youthful drinking in and around the junior year. Similarly, alcohol use and personal problems associated with drinking each exert varying degrees of influence upon the predictors within and across time, though these effects generally cluster around the junior year as well

The Effect of Thermal Increases on the Acute Toxicity of Copper and Hexavalent Chromium to Channel Catfish (Ictalurus punctatus)

48-hr, 96-hr, and incipient median tolerance limits of channel catfish (Ictalurus punctatus Rafinesque) to copper and hexavalent chromium were determined at temperatures of 50, 60, 70, and 80 F. Standard static bioassay procedures were used. The incipient TLm for copper ranged from 0.56 ppm to 2.15 ppm and from 22.5 to 39.5 ppm for hexavalent chromium. The 48-hr and 96-hr results were somewhat higher. The highest resistance for both metals occurred at 70 F. At 80 F, however, there was a sharp decrease in tolerance. Increased oxygen consumption and opercular movement offer a possible explanation since they would cause more metal to be drawn into the fish. Death from copper was attributed to destruction of the gill epithelium. Although no internal investigations were made, chromium was though to have caused death by damaging the gut epithelium. Further studies are needed to determine long-term safe levels, mechanisms of lethal action, and accumulation and elimination in the tissues

PERCEPTUAL RESPONSESOF VICTIMIZATION IN RURAL COMMUNITIES

Relationships between frequency and severity of household victimization and fears, concerns and behavioral responses to crime are investigated utilizing a mailed victimization questionnaire among a predominantly rural/farm market population. Frequency of victimization is defined as the number of personal and property offenses experienced by household members. Severity is defined as the proximity of the victim to the offense. Fear is measured by three items relating to percep tions of the relative safety of one's residential area. Concern is measured by three items relating to attitudes or percep tions about crime in general. Behavioral measures include minor avoidance reactions, such as altering entertainment practices partially in response to crime, and major avoidance or retreatist actions, such as moving in response to crime. Major findings and conclusions are as follows: (1) as the frequency and severity of victimization increases, fear of, but not concern about, crime increases; (2) though victimization appears to be an important factor in minor behavioral adaptations, this relationship is not as conclusive for major avoidance reactions; (3) fear is considered to be a rational response to people's experiential worlds; and (4) fear may be viewed as an independent consequence of both concern and victimization among the rural population sampled

Federal Court Processing of Corporate, White Collar, and Common Crime Economic Offenders Over the Past Three Decades

The history of white-collar and corporate crime in our nation has been one of toleration. Throughout much of this century, the victims, the government, and the criminal justice system have been largely inactive in attempting to control this form of law-violating behavior. Asa result, occupational and organizational crime offenders have been treated preferentially in our courts when compared to traditional or common crime offenders. Beginning in the 1970s, however, public attitudes began to changeand the government and criminal justice system were given a mandate to pursue these offenders. This paper utilizes aggregate data on the U.S. District Courts for the fiscal years ending June 30, 1964, 1974, and 1984, and is designed to investigate whethera shift in criminal justice policy (arising from public concerns over corporate and white-collar crime) has been put into effect. That is, have equitableoperational policies for the adjudicationand sentencing of corporate, white-collar, and common crime offenders evolved over the past three decades? The conclusions drawn from the data suggest that while corporate and white-collar criminals are more frequently being brought to the attention of the courts, and have beenreceiving more and moreserious sanctions, they are still receiving more lenient penalties for their actions than are common property crime offenders

Accident data issues from the TRACE perspective

Accident data issues from the TRACE perspectiv

Evaluation of Yield and Quality of Cheddar Cheese Manufactured from Milk with Added Whey Protein Concentrate

Large quantities of whey are produced as a by-product from the manufacture of cheese or casein. The United States has an annual cheese production of about 2.2 billion kg. The cheese industry has also experienced a steady increase in cheese production of about 6% a year (44). In the process, nearly 18.1 billion kg of whey are produced. Whey was once a discarded product of little value to the cheese producers. With the advent of laws and regulations governing the disposal of whey, whey became a problem that had few solutions. Even today, with the high cost of disposal and the need to reduce environmental pollution, only about 60% of the whey produced in the United States is processed (72). Concentrating and drying whey eliminates water for easier handling of the product, and increases keeping quality. By far, the single largest use of whey solids is in the form of dry whey. Dry whey powders are used as commodity ingredients mostly in human food applications (65). Use of whey proteins has been limited because of poor physical and functional properties of the commercial products. Within the last 10 years, the efficient and economical removal of the water from whey by membrane filtration has become accepted in the dairy industry. Research results have indicated some advantages for the use of ultrafiltration (UF) for removal of some of the milk serum before cheese manufacture. These include increased productivity and improved cheese yields. The largest use of membrane techniques in the dairy industry is to fractionate whey. Most research indicates that whey protein concentrates (WPC) produced by UF have superior functional properties over conventional heat coagulated wheys. The present commercial market for WPC is small, but considerable evidence indicates that more product formulation work is needed to move WPC into the general marketplace. The purpose of this research was to determine if reconstituted WPC could be used as an additive to milk for cheese making to increase yields

Crafting a critical technical practice

In recent years, the category of practice-based research has become an essential component of discourse around public funding and evaluation of the arts in British higher education. When included under the umbrella of public policy concerned with the creative industries", technology researchers often find themselves collaborating with artists who consider their own participation to be a form of practice-based research. We are conducting a study under the Creator Digital Economies project asking whether technologists, themselves, should be considered as engaging in practice-based research, whether this occurs in collaborative situations, or even as a component of their own personal research [1]

Quality Internships for Part-time Graduate Students: An Exploratory Study of a University/Agency Partnership

The university student population is changing and more students choose to complete graduate programs while working full-time and going to school part-time. Part-time graduate students, who are working towards a professional degree in the human services domain often struggle finding quality internship placements that are available during non-regular office hours. At the same time, non-profit organizations, especially those who are small and lesser known, struggle to recruit, train, and retain high quality volunteers. This is especially problematic since the number of non-profits is increasing and the number of volunteers decreasing. To look for answers both university part-time programs and non-profits must look to innovative solutions. The literature speaks of the necessity of partnerships but there is a lack of specific examples within the literature. This exploratory study describes how a partnership between a university part-time graduate program in social work and a local non-profit grief camp program for children led to a win-win situation that fulfilled the needs of both and provided future social workers with a high quality internship opportunity