Oral biopharmaceutics tools – Time for a new initiative – An introduction to the IMI project OrBiTo

Lennernäs, Hans; Aarons, Leon; Augustijns, Patrick; Beato, Stefania; Bolger, Michael B.; Box, Karl; Brewster, Marcus E.; Butler, James; Dressman, Jennifer B.; Holm, René; Frank, Kerstin; Kendall, Richard; Langguth, Peter; Sydor, Jens; Lindahl, Anders; McAllister, Mark; Muenster, Uwe; Müllertz, Anette; Ojala, K.; Pépin, Xavier; Reppas, Christos; Rostami‐Hodjegan, Amin; Verwei, Miriam; Weitschies, Werner; Wilson, Clive G.; Karlsson, Christer; Abrahamsson, Bertil

doi:10.1016/j.ejps.2013.10.012

Cited by 94 publications

(89 citation statements)

References 29 publications

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“…Indeed, this is currently performed within the IMI project OrBiTo (Oral Biopharmaceutics Tools). [38][39][40] Conclusions This study demonstrated that salts could be successfully used to improve the intestinal absorption and achieve therapeutic plasma exposure of the low-solubility basic drug candidates AZD1175 and AZD2207 in humans. It was also exemplified that the dissolution mechanisms may be significantly different even for salts of structurally similar drugs.…”

Section: Discussionmentioning

confidence: 96%

Biopharmaceutic Profiling of Salts to Improve Absorption of Poorly Soluble Basic Drugs

Tannergren

Karlsson

Sigfridsson

et al. 2016

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 96%

Biopharmaceutic Profiling of Salts to Improve Absorption of Poorly Soluble Basic Drugs

Tannergren

Karlsson

Sigfridsson

et al. 2016

Journal of Pharmaceutical Sciences

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“…In addition, one of the main goals of the Pan-European project Oral Biopharmaceutical Tools (OrBiTo), funded by the Innovative Medicines Initiative (IMI), is to provide the necessary information to improve our understanding of how orally administered drugs become absorbed from the GI tract and to generate better in vitro and in silico tools that allow a better prediction of their in vivo performance (http://www.orbitoproject.eu/objectives). Therefore, the aforementioned permeability investigations are part of the main goals of the project (76).…”

Section: Discussionmentioning

confidence: 99%

Translating Human Effective Jejunal Intestinal Permeability to Surface-Dependent Intrinsic Permeability: a Pragmatic Method for a More Mechanistic Prediction of Regional Oral Drug Absorption

Olivares‐Morales

Lennernäs

Aarons

et al. 2015

AAPS J

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Abstract. Regional intestinal effective permeability (P eff ) values are key for the understanding of drug absorption along the whole length of the human gastrointestinal (GI) tract. The distal regions of the GI tract (i.e. ileum, ascending-transverse colon) represent the main sites for GI absorption when there is incomplete absorption in the upper GI tract, e.g. for modified release formulations. In this work, a new and pragmatic method for the estimation of (passive) intestinal permeability in the different intestinal regions is being proposed, by translating the observed differences in the available mucosal surface area along the human GI tract into corrections of the historical determined jejunal P eff values. These new intestinal P eff values or Bintrinsic^P eff (P eff,int ) were subsequently employed for the prediction of the ileal absorption clearance (CL abs,ileum ) for a set of structurally diverse compounds. Additionally, the method was combined with a semimechanistic absorption PBPK model for the prediction of the fraction absorbed (f abs ). The results showed that P eff,int can successfully be employed for the prediction of the ileal CL abs and the f abs . P eff,int also showed to be a robust predictor of the f abs when the colonic absorption was allowed in the PBPK model, reducing the overprediction of f abs observed for lowly permeable compounds when using the historical P eff values. Due to its simplicity, this approach provides a useful alternative for the bottom-up prediction of GI drug absorption, especially when the distal GI tract plays a crucial role for a drug's GI absorption.KEY WORDS: intestinal permeability; oral drug absorption; physiologically based pharmacokinetic modelling.

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“…Successful drug development processes benefit from the combination of in vitro methods and in silico simulations that can predict the in vivo response (Lennernäs et al, 2014a). To enable accurate in vivo predictions from in vitro drug-release data, the drug must be released from the formulation by a similar mechanism both in vivo and in vitro (Larsen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A miniaturized in vitro release method for investigating drug-release mechanisms

Ahnfelt

Sjögren

Axén

et al. 2015

International Journal of Pharmaceutics

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We have evaluated a miniaturized in vitro method, based on the μDISS Profiler™ technique that enables on-line monitoring of drug release from a 21 μl sample with 10 ml of release medium. Four model drugs in eight clinically used formulations, including both solid and non-solid drug delivery systems, were investigated. The acquired data were compared with historical in vitro release data from the same formulations. Use of the Weibull function to describe the in vitro drug-release profiles allowed discrimination between the selected formulations with respect to the drug-release mechanisms. Comparison of the release data from the same formulation in different in vitro set-ups showed that the methodology used can affect the mechanism of in vitro release. We also evaluated the ability of the in vitro methods to predict in vivo activity by comparing simulated plasma concentration-time profiles acquired from the application of the biopharmaceutical software GI-Sim to the in vitro observations. In summary, the simulations based on the miniaturized-method release data predicted the plasma profiles as well as or more accurately than simulations based on the historical release data in 71% of the cases and this miniaturized in vitro method appears to be applicable for both solid and non-solid formulations.

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Oral biopharmaceutics tools – Time for a new initiative – An introduction to the IMI project OrBiTo

Cited by 94 publications

References 29 publications

Biopharmaceutic Profiling of Salts to Improve Absorption of Poorly Soluble Basic Drugs

Biopharmaceutic Profiling of Salts to Improve Absorption of Poorly Soluble Basic Drugs

Translating Human Effective Jejunal Intestinal Permeability to Surface-Dependent Intrinsic Permeability: a Pragmatic Method for a More Mechanistic Prediction of Regional Oral Drug Absorption

A miniaturized in vitro release method for investigating drug-release mechanisms

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