Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy

The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard

Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109935/1/cptclpt2011109.pd

Depositional constraints from detrital zircon geochronology of strata from multiple lithotectonic belts in south-central Maine, USA

The bedrock geology of south-central Maine is characterized by a series of fault-bounded lithotectonic terranes that were accreted onto the Laurentian margin during Silurian-Devonian orogenesis.  The multiple phases of deformation and metamorphism associated with this tectonism obscured most primary features in the protolith rocks, leading to uncertainties in their pre-accretionary history. Here we present the results of detrital zircon geochronology from five of these terranes and make interpretations on their depositional ages, sediment provenance, and tectonic setting of deposition.Detrital zircon from Silurian rocks of the Vassalboro Group in the eastern-most portion of the Central Maine basin indicate sediment input in an extensional setting from both Laurentian and Ordovician sources.  Results from Ordovician rocks of the Casco Bay Group of the Liberty-Orrington belt support earlier findings that these rocks have strong peri-Gondwanan affinities.  Detrital zircon from the Appleton Ridge Formation and Ghent phyllite of the Fredericton trough are consistent with a peri-Gondwanan sediment source with no evidence of Laurentian sediment input.  These findings are consistent with that of Dokken et al. (2018) for older Fredericton trough strata (i.e., Digdeguash Formation) east of the Fredericton fault in southern New Brunswick.  Two samples from the Jam Brook complex reveal extreme differences in depositional age (Ordovician vs. Mesoproterozoic) and tectonic affinity and support the hypothesis that this narrow belt represents a fault complex containing a wide variety of stratigraphic units.  Detrital zircon from Ordovician rocks of the Benner Hill Sequence indicate a peri-Gondwanan sediment source with no Laurentian input.Collectively, the pre-Silurian rocks of the Liberty-Orrington belt, Jam Brook complex, Benner Hill Sequence, and Late Ordovician-Early Silurian strata from the Appleton Ridge and Ghent phyllite in the Fredericton trough show peri-Gondwanan affinities with no evidence of Laurentian sediment input.  This suggests a barrier exisited between the Laurentian margin and these peri-Gondwanan terranes prior to about 435 Ma.  In contrast, Silurian strata from the eastern portion of the Central Maine basin do show evidence of a Laurentian sediment source, along with deposition in an extensional setting (lacking in all other samples), thus signaling a fundamental change in tectonic regime

Marketing of eastern white pine lumber from Maine and New Hampshire, Station Bulletin, no.452

The Bulletin is a publication of the New Hampshire Agricultural Experiment Station, College of Life Sciences and Agriculture, University of New Hampshire, Durham, New Hampshire

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

Intestinal Dipeptide Absorption Is Preserved During Thermal Injury and Cytokine Treatment

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142293/1/jpen0520.pd

Current land bird distribution and trends in population abundance between 1982 and 2012 on Rota, Mariana Islands

The western Pacific island of Rota is the fourth largest human-inhabited island in the Mariana archipelago and designated an Endemic Bird Area. Between 1982 and 2012, 12 point-transect distance-sampling surveys were conducted to assess bird population status. Surveys did not consistently sample the entire island; thus, we used a ratio estimator to estimate bird abundances in strata not sampled during every survey. Trends in population size were reliably estimated for 11 of 13 bird species, and 7 species declined over the 30-y time series, including the island collared-dove Streptopelia bitorquata, white-throated ground-dove Gallicolumba xanthonura, Mariana fruit-dove Ptilinopus roseicapilla, collared kingfisher Todiramphus chloris orii, Micronesian myzomela Myzomela rubratra, black drongo Dicrurus macrocercus, and Mariana crow Corvus kubaryi. The endangered Mariana crow (x̄  =  81 birds, 95% CI 30–202) declined sharply to fewer than 200 individuals in 2012, down from 1,491 birds in 1982 (95% CI  =  815–3,115). Trends increased for white tern Gygis alba, rufous fantail Rhipidura rufifrons mariae, and Micronesian starling Aplonis opaca. Numbers of the endangered Rota white-eye Zosterops rotensis declined from 1982 to the late 1990s but returned to 1980s levels by 2012, resulting in an overall stable trend. Trends for the yellow bittern Ixobrychus sinensis were inconclusive. Eurasian tree sparrow Passer montanus trends were not assessed; however, their numbers in 1982 and 2012 were similar. Occupancy models of the 2012 survey data revealed general patterns of land cover use and detectability among 12 species that could be reliably modeled. Occupancy was not assessed for the Eurasian tree sparrow because of insufficient detections. Based on the 2012 survey, bird distribution and abundance across Rota revealed three general patterns: 1) range restriction, including Mariana crow, Rota white-eye, and Eurasian tree sparrow; 2) widespread distribution, low abundance, including collared kingfisher, island collared-dove, white-throated ground-dove, Mariana fruit-dove, white tern, yellow bittern, black drongo, and Micronesian myzomela; and 3) widespread distribution, high abundance, including rufous fantail and Micronesian starling. The Mariana crow was dispersed around the periphery of the island in steep forested land-cover types. In contrast, the Rota white-eye was restricted to the high-elevation mesa. Only for the white-throated ground-dove was there a significant difference among cover types, with lower occupancy in open field than in forested areas. Vegetation was included in the best-fit occupancy models for yellow bittern, black drongo, Micronesian myzomela, and Micronesian starling, but vegetation type was not a significant variable nor included in the top models for the remaining five species: white tern, island collared-dove, Mariana fruit-dove, collared kingfisher, and rufous fantail. Given declining population trends, the Rota bird-monitoring program could benefit from establishing threshold and alert limits and identifying alternative research and management actions. Continued monitoring and demographic sampling, in conjunction with ecological studies, are needed to understand why most bird species on Rota are declining, identify the causative agents, and assess effectiveness of conservation actions, especially for the Mariana crow

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product

A Fluorescent hPept1 Transporter Substrate for Uptake Screening

Purpose. To synthesize fluorescent analogues of hPept1 substrates, FITC-Val-OCH 3 , Lys-FITC-OH, and Lys-FITC-OCH 3 , and to characterize their hPept1 transporter-mediated uptake.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41495/1/11095_2004_Article_475835.pd

A model for fire‐induced sediment yield by dry ravel in steep landscapes

Sediment flux from hillslopes to channels commonly increases following wildfires, with implications for the carbon cycle, river habitats, and debris-flow hazards. Although much of this material is transported via dry ravel, existing ravel models are not applicable to hillslopes with gradients greater than the angle of repose, which can constitute the majority of mountainous terrain. To fill this knowledge gap, we develop a continuity model for sediment storage by vegetation dams on steep hillslopes to predict sediment yields following wildfire. The maximum volume of sediment stored prior to wildfire is set to be a function of vegetation density, the capacity of plants to impound sediment, and the contributing hillslope area. Time is required after fire to establish vegetation and replenish hillslope sediment storage, which introduces vegetation regrowth rate, soil production rate, and fire recurrence interval as important variables that affect ravel yield. Model results for the San Gabriel Mountains, California, predict that sediment yield can increase by several orders of magnitude following fire. These results are consistent with field data of ravel yield (~30 mm per contributing area of hillslope in 5 months) we collected following the 2009 Station Fire, as well as postfire sediment flux recorded by 93 debris basins. In contrast to previous work, our model shows that heightened postfire sediment yields can be explained by a change in hillslope sediment storage independent of major changes in the soil production rate and landscape form over geomorphic timescales