Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media
1
Science for Life Laboratory, Department of Pharmacy, Uppsala University, Uppsala Biomedical Center P.O. Box 580, SE-75123 Uppsala, Sweden
2
Department of Pharmacy, Uppsala University, Uppsala Biomedical Center P.O. Box 580, SE-75123 Uppsala, Sweden
3
The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Uppsala Biomedical Center P.O. Box 580, SE-75123 Uppsala, Sweden
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 493; https://doi.org/10.3390/pharmaceutics12060493
Received: 6 May 2020 / Revised: 23 May 2020 / Accepted: 25 May 2020 / Published: 28 May 2020
(This article belongs to the Special Issue Mechanistic In Vitro and In Silico Modeling of Oral Drug Absorption)
The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.
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Keywords:
intrinsic dissolution rate; biorelevant dissolution media; FaSSIF; FeSSIF; poorly water-soluble drugs; physicochemical properties; controlled suspension
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Teleki, A.; Nylander, O.; Bergström, C.A. Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media. Pharmaceutics 2020, 12, 493.
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