Controlled Crystallization of the Lipophilic Drug Fenofibrate During Freeze-Drying: Elucidation of the Mechanism by In-Line Raman Spectroscopy

We developed a novel process, “controlled crystallization during freeze-drying” to produce drug nanocrystals of poorly water-soluble drugs. This process involves freeze-drying at a relatively high temperature of a drug and a matrix material from a mixture of tertiary butyl alcohol and water, resulting in drug nanocrystals incorporated in a matrix. The aim of this study was to elucidate the mechanisms that determine the size of the drug crystals. Fenofibrate was used as a model lipophilic drug. To monitor the crystallization during freeze-drying, a Raman probe was placed just above the sample in the freeze-dryer. These in-line Raman spectroscopy measurements clearly revealed when the different components crystallized during freeze-drying. The solvents crystallized only during the freezing step, while the solutes only crystallized after the temperature was increased, but before drying started. Although the solutes crystallized only after the freezing step, both the freezing rate and the shelf temperature were critical parameters that determined the final crystal size. At a higher freezing rate, smaller interstitial spaces containing the freeze-concentrated fraction were formed, resulting in smaller drug crystals (based on dissolution data). On the other hand, when the solutes crystallized at a lower shelf temperature, the degree of supersaturation is higher, resulting in a higher nucleation rate and consequently more and therefore smaller crystals. In conclusion, for the model drug fenofibrate, a high freezing rate and a relatively low crystallization temperature resulted in the smallest crystals and therefore the highest dissolution rate

Extrapulmonary tuberculosis, human immunodeficiency virus, and foreign birth in North Carolina, 1993 – 2006

<p>Abstract</p> <p>Background</p> <p>The proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important.</p> <p>Methods</p> <p>Case-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB.</p> <p>Results</p> <p>Among all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23).</p> <p>Conclusion</p> <p>Foreign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB.</p

Multimodal corpus EVA 1.0

EVA Corpus 1.0 consists of one episode of an audio/video session plus corresponding orthographic transcriptions with a duration of 57 minutes. The multi-party spontaneous discourse in the recording is from an entertaining evening TV-talk show "A si ti tut not padu", broadcasted by the POP-TV Slovene commercial TV station in 2008, and represents a part of the Slovene spoken corpus GOS (http://hdl.handle.net/11356/1040). The show contains casual conversation about general, informal and personal aspects of interviewee's life. The transcribed session of this recording has been annotated using ELAN 4.9.4. In addition to the original transcription and morphosyntactic annotation from the GOS corpus, the following layers of information are added: - statement sentiment - phrase breaks within statements - prominence of statements - sentences within the statement - sentence sentiment - sentence type - speaker visibility on the scene - gesture units - gesture phrases - emotions - semiotic intent - dialogue rol