ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2022
On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Small-Volume Dissolution Testing of Pediatric Mini-Tablets Using Miniaturized USP Apparatuses: Regulatory and Methodological Considerations.AAPS PharmSciTech · 2025Article
- Developing In Vitro-In Vivo Correlation for Bicalutamide Immediate-Release Dosage Forms with the Biphasic In Vitro Dissolution Test.Pharmaceutics · 2025Article
- Article
- Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Evaluation of a Three-Fluid Nozzle Spraying Process for Facilitating Spray Drying of Hydrophilic Polymers for the Creation of Amorphous Solid Dispersions.Pharmaceutics · 2023Article
- In Vivo Relevance of a Biphasic In Vitro Dissolution Test for the Immediate Release Tablet Formulations of Lamotrigine.Pharmaceutics · 2023Article
- Best Practices for Integration of Dissolution Data into Physiologically Based Biopharmaceutics Models (PBBM): A Biopharmaceutics Modeling Scientist Perspective.AAPS PharmSciTech · 2023Review
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A small-scale two-stage biphasic system, a small-scale two-stage dissolution-permeation system, the Erweka mini-paddle apparatus, and the BioGIT system were evaluated for their usefulness in assessing the intraluminal performance of two low solubility drugs in the fasted state, one with weakly acidic properties (tested in a salt form, diclofenac potassium) and one with weakly alkaline properties [ritonavir, tested as an amorphous solid dispersion (ASD) formulation]. In all in vitro methods, an immediate-release tablet and a powder formulation of diclofenac potassium were both rapidly dissolved in Level II biorelevant media simulating the conditions in the upper small intestine. Physiologically based biopharmaceutics (PBB) modelling for the tablet formulation resulted in a successful simulation of the average plasma profile in adults, whereas for the powder formulation modelling indicated that gastric emptying and transport through the intestinal epithelium limit the absorption rates. Detailed information on the behaviour of the ritonavir ASD formulation under both simulated gastric and upper small intestinal conditions were crucial for understanding the luminal performance. PBB modelling showed that the dissolution and precipitation parameters, estimated from the Erweka mini-paddle apparatus data and the small-scale two-stage biphasic system data, respectively, were necessary to adequately simulate the average plasma profile after administration of the ritonavir ASD formulation. Simulation of the gastrointestinal transfer process from the stomach to the small intestine was necessary to evaluate the effects of hypochlorhydric conditions on the luminal performance of the ritonavir ASD formulation. Based on this study, the selection of the appropriate in vitro method for evaluating the intraluminal performance of ionisable lipophilic drugs depends on the characteristics of the drug substance. The results suggest that for (salts of) acidic drugs (e.g., diclofenac potassium) it is only an issue of availability and ease of operation of the apparatus. For weakly alkaline substances (e.g., ritonavir), the results indicate that the dynamic dissolution process needs to be simulated, with the type of requested information (e.g., dissolution parameters, precipitation parameters, luminal concentrations) being key for selecting the most appropriate method. Regardless of the ionisation characteristics, early in the drug development process the use of small-scale systems may be inevitable, due to the limited quantities of drug substance available.
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