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The tangential flow absorption model (TFAM) - a novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives.
Eur J Pharm Biopharm. 2020 Jun 22 [Online ahead of print]EJ

Abstract

There is a substantial demand for absorptive dissolution tests, as single vessel dissolution experiments were originally not designed for testing supersaturating systems. Current approaches suffer from inadequate mass transfer of the dissolved active from the dissolution site, discrepancies in the fluid volume compared to in vivo intestinal fluid volumes or the dilution of functional excipients. In this work a novel dissolution apparatus was developed that enables adjustable mass transfer of the active through a membrane, while retaining the functional polymeric excipients at the dissolution site. Using this setup the dissolution behavior of various spray dried amorphous solid dispersions containing carbamazepine, hydrochlorothiazide and ketoconazole as model actives at intermediate and high supersaturation levels was evaluated. Compared to non-absorptive dissolution experiments, differences in concentration-time profiles were noted. The experiments with a high supersaturation of ketoconazole revealed a concentration decrease over time under absorptive conditions. Additionally, it was observed that the difference between "spring" as well as "spring and parachute" formulations was less pronounced with increasing drug efflux. Further, the apparatus was also tested with Fasted State Simulated Intestinal Fluid as dissolution medium and results were compared to phosphate buffer pH6.8. As major benefits of the new TFAM apparatus the easy experimental procedure and sample preparation for drug concentration measurements using spectroscopy in the permeate, without the necessity for additional filtration and/or centrifugation to remove precipitated drug molecules, could be highlighted. This TFAM approach seems to be a promising tool for identifying formulations for amorphous solid dispersions with optimal in vitro performance.

Authors+Show Affiliations

Division of Pharmaceutics, Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Cauerstrasse 4, 91058 Erlangen, Germany.Division of Pharmaceutics, Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Cauerstrasse 4, 91058 Erlangen, Germany.Faculty of Applied Natural Sciences, TH Koeln (Cologne University of Applied Sciences), CHEMPARK E28, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany. Electronic address: heiko.schiffter@th-koeln.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32585350

Citation

Haering, Bastian, et al. "The Tangential Flow Absorption Model (TFAM) - a Novel Dissolution Method for Evaluating the Performance of Amorphous Solid Dispersions of Poorly Water-soluble Actives." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 2020.
Haering B, Seyferth S, Schiffter HA. The tangential flow absorption model (TFAM) - a novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives. Eur J Pharm Biopharm. 2020.
Haering, B., Seyferth, S., & Schiffter, H. A. (2020). The tangential flow absorption model (TFAM) - a novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. https://doi.org/10.1016/j.ejpb.2020.06.013
Haering B, Seyferth S, Schiffter HA. The Tangential Flow Absorption Model (TFAM) - a Novel Dissolution Method for Evaluating the Performance of Amorphous Solid Dispersions of Poorly Water-soluble Actives. Eur J Pharm Biopharm. 2020 Jun 22; PubMed PMID: 32585350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The tangential flow absorption model (TFAM) - a novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives. AU - Haering,Bastian, AU - Seyferth,Stefan, AU - Schiffter,Heiko A, Y1 - 2020/06/22/ PY - 2019/12/30/received PY - 2020/05/01/revised PY - 2020/06/19/accepted PY - 2020/6/26/entrez PY - 2020/6/26/pubmed PY - 2020/6/26/medline KW - amorphous solid dispersions KW - crystallization inhibition KW - dissolution testing KW - polymers KW - poorly water-soluble actives KW - spray drying KW - tangential flow filtration JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm N2 - There is a substantial demand for absorptive dissolution tests, as single vessel dissolution experiments were originally not designed for testing supersaturating systems. Current approaches suffer from inadequate mass transfer of the dissolved active from the dissolution site, discrepancies in the fluid volume compared to in vivo intestinal fluid volumes or the dilution of functional excipients. In this work a novel dissolution apparatus was developed that enables adjustable mass transfer of the active through a membrane, while retaining the functional polymeric excipients at the dissolution site. Using this setup the dissolution behavior of various spray dried amorphous solid dispersions containing carbamazepine, hydrochlorothiazide and ketoconazole as model actives at intermediate and high supersaturation levels was evaluated. Compared to non-absorptive dissolution experiments, differences in concentration-time profiles were noted. The experiments with a high supersaturation of ketoconazole revealed a concentration decrease over time under absorptive conditions. Additionally, it was observed that the difference between "spring" as well as "spring and parachute" formulations was less pronounced with increasing drug efflux. Further, the apparatus was also tested with Fasted State Simulated Intestinal Fluid as dissolution medium and results were compared to phosphate buffer pH6.8. As major benefits of the new TFAM apparatus the easy experimental procedure and sample preparation for drug concentration measurements using spectroscopy in the permeate, without the necessity for additional filtration and/or centrifugation to remove precipitated drug molecules, could be highlighted. This TFAM approach seems to be a promising tool for identifying formulations for amorphous solid dispersions with optimal in vitro performance. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/32585350/The_tangential_flow_absorption_model_(TFAM)_-_a_novel_dissolution_method_for_evaluating_the_performance_of_amorphous_solid_dispersions_of_poorly_water-soluble_actives L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(20)30182-X DB - PRIME DP - Unbound Medicine ER -
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