Evaluation of a Three Compartment In Vitro Gastrointestinal Simulator Dissolution Apparatus to Predict In Vivo Dissolution

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109359/1/jps24112.pd

Automatic Inference of Code Transforms and Search Spaces for Automatic Patch Generation Systems

We present a new system, Genesis, that processes sets of human patches to automatically infer code transforms and search spaces for automatic patch generation. We present results that characterize the effectiveness of the Genesis inference algorithms and the resulting complete Genesis patch generation system working with real-world patches and errors collected from top 1000 github Java software development projects. To the best of our knowledge, Genesis is the first system to automatically infer patch generation transforms or candidate patch search spaces from successful patches

Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS

Alluvial to lacustrine sedimentation in an endorheic basin during the Mio-Pliocene: The Toro Negro Formation, Central Andes of Argentina

A 2400 m-thick sedimentary column belonging to the Toro Negro Formation was recorded along the Quebrada del Yeso, Sierra de Los Colorados (Vinchina Basin), La Rioja province, NW Argentina. The Vinchina basin is a good example of a closed basin surrounded by the Precordillera fold and thrust belt to the west and basement-cored blocks to the north, south (Western Sierras Pampeanas) and east (Sierra de Famatina). Seven facies associations (FA) are described and interpreted to represent fluvial, lacustrine and alluvial environments developed in the southern part of the Vinchina basin from the Late Miocene until the earliest Pleistocene. The depositional evolution of the formation was divided in four phases. Phase I (∼7–6.6 Ma) represents sedimentation in medial (FA I) to distal (FA II) parts of a southward directed distributive fluvial system with a retrogradational pattern. During phase II (6.6–6.1Ma), the distributive fluvial system was replaced by a mixed clastic-evaporitic shallow lake (FA III) in a high aggradational basin. In phase III (∼6.1–5 Ma) the eastward progradation of a fluvial system (FA IV) was recorded as a distal clastic wedge. Finally, phase IV (∼5-2.4Ma) records two depositional cycles of proximal clastic wedge progradation of fluvial-dominated piedmonts (FAV, FAVII) from the southwest (Sierra de Umango) and/or the west (Precordillera) with an intervening playa lake (FA VI). Two new U-Pb ages obtained from zircons in volcanic ash layers confirm the Late Miocene age of the lower member of the Toro Negro Formation and permit a tight correlation with the central part of the basin (Quebrada de La Troya section). The sedimentation rate calculated for the dated lacustrine-fluvial interval is higher than the corresponding one in La Troya area suggesting a higher subsidence in the southern part of the basin. During the Late Miocene (∼7-6.6Ma) the ephemeral drainage was controlled by an arid to semiarid climate and initially dissipated mostly internally as terminal fan/distributive fluvial systems descending from the north. A thick lacustrine interval developed in the southern part of the basin between ∼6.6 and 6.1 Ma during a period of high subsidence and closed drainage. Besides, this interval coincides with increased aridity recorded in other basins in the Northwest of Argentina. By ∼6.1 Ma the area started to receive the first coarse-grained sediments heralding the progradation of a clastic wedge from the southwest-west (Sierra de Umango and Precordillera) which fully developed during the rest of the Pliocene to the earliest Pleistocene (∼5–2.4 Ma). The 6.1–2.4 Ma interval records ameliorating climate conditions.Fil: Ciccioli, Patricia Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Marenssi, Sergio Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Amidon, William H.. Middlebury College; Estados UnidosFil: Limarino, Carlos Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Kylander Clark, Andrew. University of California; Estados Unido

Comparison of ibuprofen release from minitablets and capsules containing ibuprofen: β-Cyclodextrin complex

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Eur J Pharm Biopharm. 2011 May;78(1):58-66. Epub 2010 Dec 30.Mixtures containing ibuprofen (IB) complexed with b-cyclodextrin (bCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray- and freeze-drying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, bCD and IBbCD) were characterized for moisture content, densities (true and bulk), angle of repose and Carr’s index, X-ray and NMR. From physical mixtures and IBbCD complexes without other excipients were prepared 2.5-mm-diameter minitablets and capsules. Minitablets were characterized for the energy of compaction, tensile strength, friability, density and IB release (at pH 1.0 and 7.2), whereby capsules were characterized for IB release. The results from the release of IB were analyzed using different parameters, namely, the similarity factor (f2), the dissolution efficiency (DE) and the amounts released at a certain time (30, 60 and 180 min) and compared statistically (a = 0.05). The release of IB from the minitablets showed no dependency on the amount of water used in the formation of the complexes. Differences were due to the compaction force used or the presence of a shell for the capsules. The differences observed were mostly due to the characteristics of the particles (dependent on the method considered on the formation of the complexes) and neither to the dosage form nor to the complex of the IB

ETHANOL PRODUCTION FROM A MEMBRANE PURIFIED HEMICELLULOSIC HYDROLYSATE DERIVED FROM SUGAR MAPLE BY PICHIA STIPITIS NRRL Y-7124

In an effort to devise inexpensive and sustainable production of ethanol fuel, experiments were conducted to establish conditions for Pichia stipitis NRRL Y-7124 to ferment a membrane treated wood hydrolysate derived from sugar maple to produce ethanol. The degree of aeration required to effectively utilize xylose, produce ethanol, and minimize xylitol formation as well as the optimal hydrolysate concentration were the conditions examined. P. stipitis produced the highest concentrations of ethanol in shake flasks at 150 rpm (14.3 g/L in 71 h), and 50% hydrolysate maximized ethanol yield (12.4 g/L in 51.5 h). In the 50% hydrolysate cultures, P. stipitis produced ethanol at a rate of 0.24 g/Lh with a yield of 0.41 g ethanol/g wood-derived carbohydrate

Understanding Pharmaceutical Quality by Design

This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and understanding including identification of critical material attributes (CMAs); (3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and (5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review

Magnetic resonance imaging quantification of fasted state colonic liquid pockets in healthy humans

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or “pockets”. Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment

The interplay of university and industry through the FP5 network

To improve the quality of life in a modern society it is essential to reduce the distance between basic research and applications, whose crucial roles in shaping today's society prompt us to seek their understanding. Existing studies on this subject, however, have neglected the network character of the interaction between university and industry. Here we use state-of-the-art network theory methods to analyze this interplay in the so-called Framework Programme--an initiative which sets out the priorities for the European Union's research and technological development. In particular we study in the 5th Framework Programme (FP5) the role played by companies and scientific institutions and how they contribute to enhance the relationship between research and industry. Our approach provides quantitative evidence that while firms are size hierarchically organized, universities and research organizations keep the network from falling into pieces, paving the way for an effective knowledge transfer.Comment: 21 pages (including Appendix), 8 figures. Published online at http://stacks.iop.org/1367-2630/9/18