PROGRESS UPDATES

 

Mechanistic understanding of food effects: water diffusivity in gastrointestinal tract is an important parameter for the prediction of disintegration of solid oral dosage forms.

Radwan A, Ebert S, Amar A, Münnemann K, Wagner M, Amidon GL, Langguth P.

Mol Pharm. 2013 Jun 3;10(6):2283-90. doi: 10.1021/mp3006209.


Mechanistic basis for unexpected bioavailability enhancement of polyelectrolyte complexes incorporating BCS class III drugs and carrageenans.

Heinen C, Reuss S,  Saaler-Reinhardt S, Langguth P

Eur. J. Pharm. Biopharm. 85 (1): 26-33 (2013). doi:10.1016/j.ejpb.2013.03.010


Ion pairing with bile salts modulates intestinal permeability and contributes to food-drug interaction of BCS class III compound trospium chloride.

Heinen CA, Reuss S, Amidon GL, Langguth P.

Mol Pharm. 2013 Nov 4;10(11):3989-96. doi: 10.1021/mp400179v.


In vitro – in vivo correlations. General Principles and Methodologies ( Part 1)

Hühn E, Langguth P

Pharm. Ind. 75(1) 143-152 (2013)


In vitro – in vivo correlations. General Principles and Methodologies ( Part 2)

Hühn E, Langguth P

Pharm. Ind. 75(2) 312-318 (2013)


The innovative medicines initiative OrBiTo project – developing the next generation predictive tools for oral biopharmaceutics.

McAllister M., Abrahamsson B., Lennernäs H. (2014)

European Industrial Pharmacy. December 2013, Issue 19: 9-11.


Intragastric volume changes after intake of a high-caloric, high-fat standard breakfast in healthy human subjects investigated by MRI.

Koziolek M, Grimm M, Garbacz G, Kühn JP, Weitschies W.

Mol Pharm. 2014 May 5;11(5):1632-9. doi: 10.1021/mp500022u.


Oral Biopharmceutics- Current status and identified gaps of understanding.

Lennernäs H , Abrahamsson B , Langguth P

EJ Pharm. Sci. (2014) doi: 10.1016/j.ejps.2014.02.001


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

Lennernäs H, Aarons L, Augustijns P, Beato S, Bolger M, Box K, Brewster M, Butler J, Dressman J, Holm R, Julia Frank K, Kendall R, Langguth P, Sydor J, Lindahl A, McAllister M, Muenster U, Müllertz A, Ojala K, Pepin X, Reppas C, Rostami-Hodjegan A, Verwei M, Weitschies W, Wilson C, Karlsson C, Abrahamsson B.

Eur J Pharm Sci. 2014 Jun 16;57:292-9. doi: 10.1016/j.ejps.2013.10.012


Early pharmaceutical profiling to predict oral drug absorption: Current status and unmet needs.

Bergström CA, Holm R, Jørgensen SA, Andersson SB, Artursson P, Beato S, Borde A, Box K, Brewster M, Dressman J, Feng KI, Halbert G, Kostewicz E, McAllister M, Muenster U, Thinnes J, Taylor R, Mullertz A.

Eur J Pharm Sci. 2014 Jun 16;57:173-99. doi: 10.1016/j.ejps.2013.10.015.


In vitro models for the prediction of in vivo performance of oral dosage forms.

Kostewicz ES, Abrahamsson B, Brewster M, Brouwers J, Butler J, Carlert S, Dickinson PA, Dressman J, Holm R, Klein S, Mann J, McAllister M, Minekus M, Muenster U, Müllertz A, Verwei M, Vertzoni M, Weitschies W, Augustijns P.

Eur J Pharm Sci. 2014 Jun 16;57:342-66. doi: 10.1016/j.ejps.2013.08.024. Epub 2013 Aug 27.


PBPK models for the prediction of in vivo performance of oral dosage forms.

Kostewicz ES, Aarons L, Bergstrand M, Bolger MB, Galetin A, Hatley O, Jamei M, Lloyd R, Pepin X, Rostami-Hodjegan A, Sjögren E, Tannergren C, Turner DB, Wagner C, Weitschies W, Dressman J.

Eur J Pharm Sci. 2014 Jun 16;57:300-21. doi: 10.1016/j.ejps.2013.09.008. Epub 2013 Sep 21


In vivo methods for drug absorption - comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects.

Sjögren E, Abrahamsson B, Augustijns P, Becker D, Bolger MB, Brewster M, Brouwers J, Flanagan T, Harwood M, Heinen C, Holm R, Juretschke HP, Kubbinga M, Lindahl A, Lukacova V, Münster U, Neuhoff S, Nguyen MA, Peer Av, Reppas C, Hodjegan AR, Tannergren C, Weitschies W, Wilson C, Zane P, Lennernäs H, Langguth P.

Eur J Pharm Sci. 2014 Jun 16;57:99-151. doi: 10.1016/j.ejps.2014.02.010.


Use of the pentagastrin dog model to explore the food effects on formulations in early drug development.

Zane P, Guo Z, MacGerorge D, Vicat P, Ollier C.

Eur J Pharm Sci. 2014 Jun 16;57:207-13. doi: 10.1016/j.ejps.2013.09.018. Epub 2013 Oct 1


Bio-predictive tablet disintegration: effect of water diffusivity, fluid flow, food composition and test conditions.

Radwan A, Wagner M, Amidon GL, Langguth P

Eur J Pharm Sci. 2014 Jun 16;57:273-9. doi: 10.1016/j.ejps.2013.08.038.


The Biohharmaceutics classification system: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC.

Tsume Y, Mudie D, Langguth P, Amidon G, Amidon G

E J Pharm Sci. 2014) doi: 10.1016/j.ejps.2014.01.009


Improvement of trospium-specific absorption models for fasted and fed states in humans.

Cvijić S, Langguth P.

Biopharm Drug Dispos. 2014 Jul 17. doi: 10.1002/bdd.1911. [Epub ahead of print]


Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification.

Cvijić S, Parojčić J, Langguth P.

Eur J Pharm Sci. 2014 Sep 30;61:40-53. doi: 10.1016/j.ejps.2014.04.008


Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: Lactose in solid oral dosage forms.

Kubbinga M, Moghani L, Langguth P.

Eur J Pharm Sci. 2014 Sep 30;61:27-31. doi: 10.1016/j.ejps.2014.03.008. Epub 2014 Apr 13


Resolving intraluminal drug and formulation behaviour: gastrointestinal concentration profiling in humans.

Brouwers J, Augustijns P

EJ Pharm Sci. 2014 Sept 30: Volume 61, Pages 2-10. doi:10.1016/j.ejps.2014.01.010


Gastrointestinal transfer: In vivo evaluation and implementation in in vitro and in silico predictive tools.

Hens B, Brouwers J, Anneveld B, Corsetti M, Symillides M, Vertzoni M, Reppas C, Turner DB, Augustijns P.

Eur J Pharm Sci. 2014 Oct 15;63:233-42. doi: 10.1016/j.ejps.2014.07.008.


Direct In Vivo Human Intestinal Permeability (Peff ) Determined with Different Clinical Perfusion and Intubation Methods.

Dahlgren D, Roos C, Sjögren E, Lennernäs H.

J Pharm Sci. 2014 Nov 19. doi: 10.1002/jps.24258. [Epub ahead of print]


Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of Biopharmaceutics Classification System Class II drugs

Khadra I, Zhou Z, Dunn C, Wilson CG, Halbert G.

Eur J Pharm Sci. 2015 Published online: 22-Nov-2014: 65-75 doi: 10.1016/j.ejps.2014.10.019


Gastrointestinal transfer: in vivo evaluation and implementation in in vitro and in silico predictive tools

Hens B, Brouwers J, Anneveld B, Corsetti M, Symillides M, Vertzoni M, Reppas C, Turner DB, Augustijns P.

Eur J Pharm Sci. 2014 Oct 15;63:233-42. doi: 10.1016/j.ejps.2014.07.008. Epub 2014 Jul 23.


Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap(®) System

Koziolek M, Grimm M, Becker D, Iordanov V, Zou H, Shimizu J, Wanke C, Garbacz G, Weitschies W.

J Pharm Sci. 2014 Nov 19. doi: 10.1002/jps.24274. [Epub ahead of print]


Intragastric volume changes after intake of a high-caloric, high-fat standard breakfast in healthy human subjects investigated by MRI 

Koziolek M, Grimm M, Garbacz G, Kühn JP, Weitschies W.

Mol Pharm. 2014 May 5;11(5):1632-9. doi: 10.1021/mp500022u. Epub 2014 Apr 15


Oral solid dosage form disintegration – The forgotten test

J. Al-Gousous and P. Langguth

J Pharm Sci. 2014 Dec 24. doi: 10.1002/jps.24303. [Epub ahead of print]


Dissolution of mesalazine modified release tablets under standard and bio-relevant test conditions

Garbacz G, Rappen GM, Koziolek M, Weitschies W.

J Pharm Pharmacol. 2015 Feb;67(2):199-208. doi: 10.1111/jphp.12332. Epub 2014 Dec 31.


The Influence of Chitosan on the Oral Bioavailability of Acyclovir-a Comparative Bioavailability Study in Humans

Kubbinga M, Nguyen MA, Staubach P, Teerenstra S, Langguth P.

Pharm Res. 2015 Jan 22. [Epub ahead of print]


Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data.

Sjögren E, Dahlgren D, Roos C, Lennernäs H

Mol Pharm. 2015 Jun 1;12(6):2026-39. doi: 10.1021/mp500834v. Epub 2015 May 6.


In vitro simulation of luminal conditions of performance of oral drug products choosing the appropriate test media.

Markopoulos C, Andreas C, Vertzoni M, Dressman J, Reppas C

E J Pharm Bio. 2015 June: Volume 93, pp 173-182. doi:10.1016/j.ejpb.2015.03.009


European versus United States Pharmacopeia Disintegration Testing Methods for Enteric-Coated Soft Gelatin Capsules

Al-Gousous J, Langguth P.

Dissolution Technologies 2015 Aug.  dx.doi.org/10.14227/DT220315P6 


Development of a high-throughput in vitro lipolysis model for rapid screening of lipid-based drug delivery systems.

Mosgaard M, Sassene P, Mu H, Rades T, Müllertz A

E J Pharm. Bio. 2015 August: Volume 94, pp 493-500. doi:10.1016/j.ejpb.2015.06.028


Oral solid dosage form disintegration - The forgotten test

Al-Gousous J, Langguth P

J Pharm Sci. 2015 Sept: Volume 104, Issue 9, pp 2664-2675. DOI: 10.1002/jps.24303


Investigation of pH and temperature profiles in the GI-tract of fasted human subjects using the IntelliCap® system.

Koziolek M, Grimm M, Becker D, Iordanov V, Zou H, Shimizu J, Wanke C, Garbacz G, Weirschies W

J Pharm Sci. 2015 Sept: Volume 104, Issue 9, pp2855-2863. DOI: 10.1002/jps.24274


Computational fluid dynamics simulation of hydrodynamics and stresses in the PhEur/USP disintegration tester under fed and fasted fluid characteristics.

Kindgen S, Wachtet H, Abrahamsson B, Langguth P

J Pharm Sci. 2015 Sept: Volume 104, Issue 9, pp 2956-2968. DOI: 10.1002/jps.24511


Two-stage single-compartment models to evaluate dissolution in lower intestine.

Markopoulos C, Vertzoni M, Symillides M, Kesisoglou F, Reppas C

J Pharm Sci. 2015 September: Volume 104, Issue 9, pp 2986-2997. DOI: 10.1002/jps.24485


Gastrointestinal behavior of nano- and micronized fenofibrate: in vivo evaluation in man and in vitro assessment of the permeation potential.

Hens B, Brouwers J, Corsetti M, Augustijns P

E J  Pharm. Sci. 2015 Sept 18: Volume 77, Pages 40-47. doi:10.1016/j.ejps.2015.05.023


Characterization of contents of distal ileum and cecum to which drugs/drug products are exposed during BA/BE studies in healthy adults.

Reppas C, Karatza E, Goumas C, Markolpoulos C, Vertzoni

Pharm. Research. 2015 Oct, Volume 32, Issue 10, pp 3338-3349. 10.1007/s11095-015-1710-6


Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations.

Gesquiere I, Darwich A, Schueren B, Hoon J, Lannoo M, Matthys C, Rostami A, Foulon V, Augustijn P

BJCP. 2015 Nov: Volume 80, Issue 5, pp 1021-1030. DOI: 10.1111/bcp.12666


In vitro biorelevant models for evaluating modified release mesalamine products for forecasting effect of formulation and meal intake on drug release.

Andreas C, Chen Y, Markopoulos C, Reppas C, Dressman J

E J Pharm. & BioPharm. 2015 Nov: Volume 97, Part A, pp 39-50. doi:10.1016/j.ejpb.2015.09.002


Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies.

Koziolek M, Schneider F, Grimm M, Modeβ C, Seekamp A, Roustom T, Siegmund W,Weitschies W.​

2015 Dec 28;220(Pt A):71-8. doi: 10.1016/j.jconrel.2015.10.022.

 

Hens B, Corsetti M, Brouwers J, Augustijns P

J Pharm Sci. 2016 May 10. doi:10.1016/j.xphs.2016.03.027


Effectiveness of supersaturation promoting excipients on luminal albendazole concentrations following in complete gastric dissolution in fasted healthy adults.

Kourentas A, Vertzoni M, Symillides M, Goumas K, Gibbon R, Butler J, Reppas C

E J Pharm Sci. 2016 May 13. doi:10.1016/j.ejps.2016.05.013


An in vitro biorelevant gastrointestinal transfer (BioGIT) system for forecasting concentrations in the fasted upper small intestine: Design, implementation and evaluation.

Kourentas A, Vertzoni M, Stavrinoudakis N, Symillidis A, Brouwers J, Augustijns P, Reppas C, Symillides M

E J Pharm Sci. 2016 Jan 20. doi:10.1016/j.ejps.2015.11.012


Gastrointestinal behavior of weakly acidic BCS class II drugs in man - case study diclofenac potassium.

Abeele J, Brouwers J, Mattheus R, Tack J, Augustijns P

J Pharm Sci. 2015 Sept. DOI: 10.1002/jps.24647


Elucidating the Molecular Interactions Occurring during Drug Precipitation of Weak Bases from Lipid-Based Formulations: A Case Study with Cinnarizine and a Long Chain Self-Nanoemulsifying Drug Delivery System.

Sassene PJ, Mosgaard M, Löbmann K, Mu H, Larsen F, Rades T, Müllertz A

Mol. Pharmaceutics, 2015, 12 (11), pp 4067–4076. DOI: 10.1021/acs.molPharmaceut.5b00498


Supersaturation and precipitatioin of posaconazole upon entry in the upper small intestine in humans.

Hens B, Brouwers J, Corsetti M, Augustijns P

J Pharm Sci. 2015 Oct 27. doi: 10.1002/jps.24690


Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper GI tract (TIM-1 and tiny TIM) for investigating the bioaccessibility of Pharm.ceutical compounds from oral dosage forms.

Verwei M, Minekus M, Zeijdner E, Schilderink R, Havenaar R

Int J Pharm. 2016 Feb 10: Volume 498, Issues 1-2, pp 178-186. doi:10.1016/j.ijpharm.2015.11.048


Meta-Analysis of Magnetic Marker Monitoring data to characterize the movement of single unit dosage forms though the gastrointestinal tract under fed and fasting conditions.

Hénin E, Bergstrand M, Weitschies W, Karlsson M

Pharm. Research. 2016 March. Volume 33, Issue 3, pp 751-762. doi:10.​1007/​s11095-015-1824-x


Semi-mechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes.

Alskär O, Bagger J, Røge R, Knop F, Karlsson M, Visbøll, Kjellsson M

J Clin Pharmacol. 2016 Mar;56(3):340-8. doi: 10.1002/jcph.602. Epub 2015 Oct 12


Koziolek M, Grimm M, Schneider F, Jedamzik P, Sager M, Kühn JP, Siegmund W, Weitschies W.

Adv Drug Deliv Rev. 2016 Jun 1;101:75-88.doi: 10.1016/j.addr.2016.03.009.


Effectiveness of supersaturation promoting excipients on albendazole concentrations in upper gastrointestinal lumen of fasted healthy adults.

Kourentas A, Vertzoni M, Symillides M, Goumas K, Gibbon R, Butler J, Reppas C.

Eur J Pharm Sci. 2016 Aug 25;91:11-9. doi: 10.1016/j.ejps.2016.05.013.


Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

Kourentas A, Vertzoni M, Khadra I, Symillides M, Clark H, Halbert G, Butler J,Reppas C.

J Pharm Sci. 2016 Sep;105(9):2896-903. doi: 10.1016/j.xphs.2016.04.037.


Regional Intestinal Permeability of Three Model Drugs in Human.

Dahlgren D, Roos C, Lundqvist A, Abrahamsson B, Tannergren C, Hellström PM, Sjögren E, Lennernäs H.

Mol Pharm. 2016 Sep 6;13(9):3013-21. doi: 10.1021/acs.molpharmaceut.6b00514.


The dynamic gastric environment and its impact on drug and formulation behaviour.

Van Den Abeele J, Rubbens J, Brouwers J, Augustijns P.

Eur J Pharm Sci. 2016 Sep 2. pii: S0928-0987(16)30349-9. doi: 10.1016/j.ejps.2016.08.060.


Gastrointestinal and Systemic Monitoring of Posaconazole in Humans After Fasted and Fed State Administration of a Solid Dispersion.

Hens B, Corsetti M, Brouwers J, Augustijns P.

J Pharm Sci. 2016 Sep;105(9):2904-12. doi: 10.1016/j.xphs.2016.03.027.


Resolving the physiological conditions in bioavailability and bioequivalence studies: comparison of fasted and fed state.

Schneider F, Grimm M, Koziolek M, Modeß C, Dokter A, Roustom T, Siegmund W, Weitschies W.

Eur J Pharm Biopharm. 2016 Sep 14. pii: S0939-6411(16)30558-6. doi: 10.1016/j.ejpb.2016.09.009.


Supersaturation and Precipitation of Posaconazole Upon Entry in the Upper Small Intestine in Humans.

Hens B, Brouwers J, Corsetti M, Augustijns P.

J Pharm Sci. 2016 Sep;105(9):2677-84. doi: 10.1002/jps.24690