Continuous blending of dry pharmaceutical powders

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 269-279).Conventional batch blending of pharmaceutical powders coupled with long quality analysis times increases the production cycle time leading to strained cash flows. Also, scale-up issues faced in process development causes delays in transforming a drug in research to a drug under commercial production. Continuous blending is as an attractive alternative design choice to batch process and is examined in this work. This work proposes to examine the feasibility of applying continuous blending in pharmaceutical manufacturing. Two kinds of blenders, a double helical ribbon blender and a Zigzag R blender were chosen as experimental systems representing high shear and moderate shear equipment. This work first focuses on developing a process understanding of continuous blending by examining the ow behavior of powders in experimental blenders using impulse stimulus response experiments and subsequent residence time distribution analysis. Powder ow behavior was modeled using an residence time distribution models like axial dispersion models. These ow behavior studies were followed by blender performance studies. The dependence of the mixing performance of the continuous blending system on different operational variables like rotation rates of mixing elements and raw material properties like particle size, shape and cohesion were studied. Mean residence time and time period of fluctuation in the concentration of active ingredient coming at the inlet were the two most important operational variables that affected blender performance. Larger particles and particles with less cohesion were seen to mix well with higher dispersion coefficients in a ribbon blender. A residence time distribution based process model for continuous blending was investigated and shown to depict the process well within experimental errors in determining the parameters of the residence time distribution model.(cont.) The predictive capability of the process model was found to dependent on the scale of scrutiny of the powder mixture in the blender. Choosing the correct scale of scrutiny was demonstrated to be of critical importance in determination of blend quality. Growing pressures on pharmaceutical industry due to patent expirations has forced manufacturers to look beyond the US and EU for potential manufacturing locations in addition to invest in novel manufacturing methods and technologies. The capstone work in this thesis proposes a framework that managers of pharmaceutical and biologics manufacturing can utilize to identify critical issues in globalization of manufacturing and in making strategic manufacturing location decisions.by Lakshman Pernenkil.Ph.D

Transvenous right ventricular pacing in a patient with tricuspid mechanical prosthesis

We report a patient in whom permanent endocardial pacing was accomplished by passage of the electrode through a mechanical tricuspid valve. Echocardiography study showed a minimal tricuspid regurgitation

A review of current techniques for the evaluation of powder mixing

Blending a mixture of powders to a homogeneous system is a crucial step in many manufacturing processes. To achieve a high quality of the end product, powder mixtures should be made with high content uniformity. For instance, producing uniform tablets depends on the homogeneous dispersion of active pharmaceutical ingredient (API), often in low level quantities, into excipients. To control the uniformity of a powder mixture, the first required step is to estimate the powder content information during blending. There are several powder homogeneity evaluation techniques which differ in accuracy, fundamental basis, cost and operating conditions. In this article, emerging techniques for the analysis of powder content and powder blend uniformity, are explained and compared. The advantages and drawbacks of all the techniques are reviewed to help the readers to select the appropriate equipment for the powder mixing evaluation. In addition, the paper highlights the recent innovative on-line measurement techniques used for the non-invasive evaluation of the mixing performance

Trends in breast and colorectal cancer screening among U.S. adults by race, healthcare coverage, and SES before, during, and after the great recession

The aim of this study is examine trends in breast and colorectal cancer screening in the U.S. by race, healthcare coverage, and socio-economic status (SES) before the Great Recession (2003–2005), during the recession (2007–2009), and post-recession/Affordable Care Act (ACA) period (2010−2012). Data on a representative sample of U.S. adults was obtained from the Behavioral Risk Factor Surveillance System (BRFSS). Breast and colorectal cancer screening were defined in line with U.S. Preventative Services Task Force guidelines, and survey weighted statistical methods were utilized to analyze trends in cancer screening among 1,858,572 BRFSS participants. Overall, 83% of women received mammograms in the past 2 years, while 95% of adults received colorectal cancer screening in the past 10 years. Compared with the pre-recession period, the odds of colorectal screening within 5 years were slightly higher during the recession (OR: 1.05, 95% CI: 1.03–1.08) but significantly lower in the post-recession/ACA period (OR: 0.73, 95% CI: 0.72–0.75). Odds of mammography screening were lower during (OR: 0.94,95% CI: 0.91–0.96) and post-recession/ACA period (OR: 0.80, 95% CI: 0.78–0.82). Breast cancer screening rates declined in the recession and post-recession, while colorectal cancer screening rates increased during the recession and decreased post-recession. Low SES adults and those without healthcare coverage were the least likely to receive screening

MANAGEMENT CONTROL SYSTEMS - Make or Break?

Due to the increase in M&A’s more implementations are conducted, a focus for any implementation is to have the company’s control system in place throughout the whole organization, including the new parts. Even though there is an increase in implementations of MCS the existing research in this field is lacking. There are studies showing influencing factors on corporation, culture being the main factor but it is unclear if this influence extend to implementation processes and especially MCS with their high amount of structure. To answer the research question “Can culture be the main part that makes or breaks implementation of management control systems?” a case study of an implementation will be used and information from that case will be put against theories on management control systems and culture’s influence on corporations. The conclusions drawn in this thesis can show that MCS are influenced by culture, the most affected part being personnel control. Depending on the case culture can break the implementation of MCS, especially when culture is not handled during the implementation