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Open AccessArticle

High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

1
Drug Transport & Delivery Group, Department of Physics, Chemistry & Pharmacy, University of Southern Denmark, 5230 Odense, Denmark
2
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 30-6088 Krakow, Poland
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 227; https://doi.org/10.3390/pharmaceutics11050227
Received: 9 April 2019 / Revised: 1 May 2019 / Accepted: 7 May 2019 / Published: 10 May 2019
Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeation employing a two-compartment 96-well plate. Freeze-drying from hydro-alcoholic solutions was used to prepare amorphous formulations. The screening approach was tested on amorphous and crystalline tadalafil formulations with and without Soluplus®. The workflow consisted of: (1) dispersion of the formulations; (2) incubation within the two-compartment plate, where a dialysis membrane separated donor (dispersed formulation) and acceptor; (3) sampling (donor and acceptor), where donor samples were centrifuged to remove non-dissolved material; and (4) quantification by UHPLC-UV. To identify optimal screening conditions, the following parameters were varied: dispersion medium (buffer/biomimetic media), acceptor medium (buffer/surfactant solutions), and incubation time (1, 3, and 6 h). Surfactants (acceptor) increased tadalafil permeation. Biomimetic medium (donor) enhanced dissolution, but not permeation, except for freeze-dried tadalafil, for which the permeated amount increased. The predictiveness was evaluated by comparing dissolution-/permeation-results with in vivo bioavailability. In general, both dissolution and permeation reflected bioavailability, whereof the latter was a better predictor. High-throughput dissolution/permeation is regarded promising for formulation screening. View Full-Text
Keywords: solubility; dissolution; supersaturation; solubilization; permeability; biomimetic; sink; high-throughput screening; amorphous solid dispersions solubility; dissolution; supersaturation; solubilization; permeability; biomimetic; sink; high-throughput screening; amorphous solid dispersions
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MDPI and ACS Style

Jacobsen, A.-C.; Krupa, A.; Brandl, M.; Bauer-Brandl, A. High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach. Pharmaceutics 2019, 11, 227.

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