The Experts below are selected from a list of 81798 Experts worldwide ranked by ideXlab platform

Arik Dahan - One of the best experts on this subject based on the ideXlab platform.

  • the biopharmaceutics of successful controlled release drug product segmental dependent permeability of glipizide vs metoprolol throughout the intestinal tract
    International Journal of Pharmaceutics, 2015
    Co-Authors: Moran Zur, Noa Cohen, Riad Agbaria, Arik Dahan
    Abstract:

    Abstract The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility Class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability Class Boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol’s jejunal permeability. We present an analysis that identifies metoprolol’s jejunal permeability as the low/high permeability Class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form.

  • The Low/High BCS Permeability Class Boundary: Physicochemical Comparison of Metoprolol and Labetalol
    Molecular pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

  • the low high bcs permeability Class Boundary physicochemical comparison of metoprolol and labetalol
    Molecular Pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

  • Regional-Dependent Intestinal Permeability and BCS Classification: Elucidation of pH-Related Complexity in Rats Using Pseudoephedrine
    Aaps Journal, 2013
    Co-Authors: Moran Fairstein, Rotem Swissa, Arik Dahan
    Abstract:

    Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (Peff) Class Boundary, pseudoephedrine was provisionally Classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (Fabs) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized Peff–Fabs correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine’s BCS Classification. Pseudoephedrine’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine’s permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine’s complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between Peff and Fabs is involved in its absorption. Rather, it reflects the complexity behind Peff when considering the whole of the intestine. We propose to allow high-permeability Classification to drugs with Peff that matches/exceeds the low/high Class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

  • The fraction dose absorbed, in humans, and high jejunal human permeability relationship.
    Molecular Pharmaceutics, 2012
    Co-Authors: Arik Dahan, Hans Lennernäs, Gordon L Amidon
    Abstract:

    The drug intestinal permeability (Peff) measure has been widely used as one of the main factors governing both the rate and/or extent of drug absorption (Fabs) in humans following oral administration. In this communication we emphasize the complexity behind and the care that must be taken with this in vivo Peff measurement. Intestinal permeability, considering the whole of the human intestine, is more complex than generally recognized, and this can lead to misjudgment regarding Fabs and Peff in various settings, e.g. drug discovery, formulation design, drug development and regulation. Setting the adequate standard for the low/high permeability Class Boundary, the different experimental methods for the permeability measurement, and segmental-dependent permeability throughout the human intestine due to different mechanisms are some of the main points that are discussed. Overall, the use of jejunal Peff as a surrogate for extent of absorption is sound and scientifically justified; a compound with high jejuna...

Gordon L Amidon - One of the best experts on this subject based on the ideXlab platform.

  • The Low/High BCS Permeability Class Boundary: Physicochemical Comparison of Metoprolol and Labetalol
    Molecular pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

  • the low high bcs permeability Class Boundary physicochemical comparison of metoprolol and labetalol
    Molecular Pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

  • Comparison of the Permeability of Metoprolol and Labetalol in Rat, Mouse and Caco-2 Cells: Use as a Reference Standard for BCS Classification
    Molecular Pharmaceutics, 2013
    Co-Authors: Tuba Incecayir, Yasuhiro Tsume, Gordon L Amidon
    Abstract:

    The purpose of this study was to investigate labetalol as a potential high permeability reference standard for the application of Biopharmaceutics Classification Systems (BCS). Permeabilities of labetalol and metoprolol were investigated in animal intestinal perfusion models and Caco-2 cell monolayers. After isolating specific intestinal segments, in situ single-pass intestinal perfusions (SPIP) were performed in rats and mice. The effective permeabilities (Peff) of labetalol and metoprolol, an FDA standard for the low/high Peff Class Boundary, were investigated in two different segments of rat intestine (proximal jejunum and distal ileum) and in the proximal jejunum of mouse. No significant difference was found between Peff of metoprolol and labetalol in the jejunum and ileum of rat (0.33 ± 0.11 × 10–4 vs 0.38 ± 0.06 × 10–4 and 0.57 ± 0.17 × 10–4 vs 0.64 ± 0.30 × 10–4 cm/s, respectively) and in the jejunum of mouse (0.55 ± 0.05 × 10–4 vs 0.59 ± 0.13 × 10–4 cm/s). However, Peff of metoprolol and labetalol...

  • The fraction dose absorbed, in humans, and high jejunal human permeability relationship.
    Molecular Pharmaceutics, 2012
    Co-Authors: Arik Dahan, Hans Lennernäs, Gordon L Amidon
    Abstract:

    The drug intestinal permeability (Peff) measure has been widely used as one of the main factors governing both the rate and/or extent of drug absorption (Fabs) in humans following oral administration. In this communication we emphasize the complexity behind and the care that must be taken with this in vivo Peff measurement. Intestinal permeability, considering the whole of the human intestine, is more complex than generally recognized, and this can lead to misjudgment regarding Fabs and Peff in various settings, e.g. drug discovery, formulation design, drug development and regulation. Setting the adequate standard for the low/high permeability Class Boundary, the different experimental methods for the permeability measurement, and segmental-dependent permeability throughout the human intestine due to different mechanisms are some of the main points that are discussed. Overall, the use of jejunal Peff as a surrogate for extent of absorption is sound and scientifically justified; a compound with high jejuna...

  • High-Permeability Criterion for BCS Classification: Segmental/pH Dependent Permeability Considerations
    Molecular Pharmaceutics, 2010
    Co-Authors: Arik Dahan, Jonathan M. Miller, Lawrence X Yu, John M Hilfinger, Hans Lennernäs, Shinji Yamashita, Gordon L Amidon
    Abstract:

    The FDA Classifies a drug substance as high-permeability when the fraction of dose absorbed (Fabs) in humans is 90% or higher. This direct correlation between human permeability and Fabs has been recently controversial, since the β-blocker sotalol showed high Fabs (90%) and low Caco-2 permeability. The purpose of this study was to investigate the scientific basis for this disparity between permeability and Fabs. The effective permeabilities (Peff) of sotalol and metoprolol, a FDA standard for the low/high Peff Class Boundary, were investigated in the rat perfusion model, in three different intestinal segments with pHs corresponding to the physiological pH in each region: (1) proximal jejunum, pH 6.5; (2) mid small intestine, pH 7.0; and (3) distal ileum, pH 7.5. Both metoprolol and sotalol showed pH-dependent permeability, with higher Peff at higher pH. At any given pH, sotalol showed lower permeability than metoprolol; however, the permeability of sotalol determined at pH 7.5 exceeded/matched metoprolol’...

Moran Zur - One of the best experts on this subject based on the ideXlab platform.

  • the biopharmaceutics of successful controlled release drug product segmental dependent permeability of glipizide vs metoprolol throughout the intestinal tract
    International Journal of Pharmaceutics, 2015
    Co-Authors: Moran Zur, Noa Cohen, Riad Agbaria, Arik Dahan
    Abstract:

    Abstract The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility Class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability Class Boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol’s jejunal permeability. We present an analysis that identifies metoprolol’s jejunal permeability as the low/high permeability Class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form.

  • The Low/High BCS Permeability Class Boundary: Physicochemical Comparison of Metoprolol and Labetalol
    Molecular pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

  • the low high bcs permeability Class Boundary physicochemical comparison of metoprolol and labetalol
    Molecular Pharmaceutics, 2014
    Co-Authors: Moran Zur, Gordon L Amidon, Marisa Gasparini, Omri Wolk, Arik Dahan
    Abstract:

    Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability Class Boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability Class reference drug. Labetalol’s BCS solubility Class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5–7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol–buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitr...

Erik Olin Wright - One of the best experts on this subject based on the ideXlab platform.

  • The Permeability of Class Boundaries to Intergenerational Mobility Among Men in the United-States, Canada, Norway and Sweden
    American Sociological Review, 1994
    Co-Authors: Mark Western, Erik Olin Wright
    Abstract:

    We explore the differential permeability of three Class boundaries-the boundaries determined by property, authority and expertise-to intergenerational mobility among men in four developed capitalist economies: the United States, Canada, Norway and Sweden. We conclude: (1) In all four countries, the authority Boundary is the most permeable to intergenerational mobility; (2) in the two North American countries, the patterns of permeability of Class boundaries are broadly consistent with the expectations of neo-Marxist conceptualizations of Class-the property Boundary is the least permeable, followed by the expertise Boundary, and then the authority Boundary; (3) in the two Scandinavian countries, especially in Sweden, the property and expertise boundaries do not differ significantly in their degree of permeability; (4) the Class Boundary between workers and capitalists is less permeable than would be predicted from a strictly additive model of the permeability of the three dimensions of the Class structure (property + authority + expertise); and (5) in the United States and Canada, the patterns of Class Boundary permeability to mobility are similar to the patterns of permeability to friendship and crossClass marriages, while mobility patterns in Norway and Sweden differ from friendship

  • The Relative Permeability of Class Boundaries to Cross-Class Friendships: A Comparative Study of the United States, Canada, Sweden, and Norway
    American Sociological Review, 1992
    Co-Authors: Erik Olin Wright, Donmoon Cho
    Abstract:

    The structural analysis of Classes can be divided into the analysis of Class locations and the analysis of permeability of boundaries separating those locations. Marxist analysis of Class structure has been primarily concerned with the first of these while Weberian Class analysis has focused on the second. We attempt to combine a Marxist structural Class concept, which views Class locations in capitalist societies as structured by exploitation based on property relations, authority relations and expertise, with the Weberian concern with the ways lives of individuals traverse the boundaries of that structure. We examine patterns of friendship ties across Class boundaries in four contemporary capitalist societies: the United States, Canada, Sweden, and Norway. Three empirical conclusions stand out: (1) The property-based Class Boundary is the least permeable of the three exploitation dimensions; (2) the authority-based Class Boundary is significantly more permeable than the expertise-based Boundary; and (3) patterns of inter-Class friendships are largely invariant across these four countries.

Feng Wang - One of the best experts on this subject based on the ideXlab platform.

  • an accelerator for support vector machines based on the local geometrical information and data partition
    International Journal of Machine Learning and Cybernetics, 2019
    Co-Authors: Yunsheng Song, Jiye Liang, Feng Wang
    Abstract:

    The support vector machines (SVM) is difficult to deal with large datasets for its low training efficiency. One of the important solutions has been developed by dividing a whole dataset into smaller subsets with data partition and combining the results of the Classifiers over the divided subsets. However, traditional data partition approaches are difficult to preserve the Class Boundary of the dataset or control the size of divided subsets, so that their performance will be greatly influenced. To overcome this difficulty, we propose an accelerator for SVM algorithm based on the local geometrical information. In this algorithm, the feature space is divided into several regions with the approximately equal number of training instances by linear projection, and then each SVM Classifier trained over the extended region only predicts the unlabeled instances within that original region. The proposed algorithm can not only hold the decision Boundary of the raw data, but also saves a lot of execution time for implementing it in a parallel environment. Furthermore, the number of instances within each divided regions can be effectively controlled; it is conducive to choose the complexity of the execution in each of the processors. Experiments show that the Classification performance of the proposed algorithm compares favorably with four state-of-the-art algorithms with the least training time.