Academic Journal
Simulation-guided dissolution testing: Coupling DDDPlus™ and GastroPlus® to predict aripiprazole oral bioperformance
| Title: | Simulation-guided dissolution testing: Coupling DDDPlus™ and GastroPlus® to predict aripiprazole oral bioperformance |
|---|---|
| Authors: | Krstevska, Aleksandra, Nedelkov, Ivana, Petrović, Maša, Ivković, Branka, Dobričić, Vladimir, Cvijić, Sandra |
| Source: | Journal of Drug Delivery Science and Technology |
| Publisher Information: | Elsevier BV, 2026. |
| Publication Year: | 2026 |
| Subject Terms: | DDDPlus™, Solubility, Biopredictive dissolution, Aripiprazole, GastroPlus®, Permeability |
| Description: | Orally administered weakly basic compounds like aripiprazole (ARI) can precipitate in the small intestine due to limited solubility at intestinal pH. This study aimed to identify in vitro biopredictive dissolution tests conditions for ARI immediate release (IR) tablets using a combined GastroPlus® (G+) and DDDPlus™ (D+) modeling approach. ARI solubility was studied in vitro across various pH levels and in biorelevant media, while passive permeability was evaluated using the PAMPA model. These experimental data were used as inputs to build an ARI-specific G+ model, which was used to estimate the in vivo dissolution profiles of ARI following oral administration of IR tablets. D+ was then used to identify in vitro dissolution test conditions predictive of the G+ simulated in vivo dissolution profiles. The in vitro dissolution data for 10 mg, 15 mg and 30 mg ARI IR tablets in 900 mL of compendial media (pH 1.0, pH 4.5 and pH 6.8) using paddle apparatus at 50 rpm and 75 rpm were employed for D+ model development and validation. Experimental findings classified ARI as a low soluble, borderline highly permeable compound. G+ simulations revealed dose-dependent intestinal precipitation followed by subsequent re-dissolution. A three-stage, pH shift dissolution method using basket apparatus was identified as biopredictive of G+ estimated in vivo dissolution profiles, effectively mimicking the G+ simulated precipitation and re-dissolution. This work illustrates an example of how integrated dissolution and absorption modeling can be leveraged to identify biorelevant in vitro test conditions. |
| Document Type: | Article |
| DOI: | 10.1016/j.jddst.2025.107621 |
| Access URL: | https://farfar.pharmacy.bg.ac.rs/handle/123456789/6287 |
| Accession Number: | edsair.od......4877..8337deac47bab64b485c0bc8d0c78b60 |
| Database: | OpenAIRE |
Be the first to leave a comment!