Quality Control Dissolution Data Is Biopredictive for a Modified Release Ropinirole Formulation: Virtual Experiment with the Use of Re-Developed and Verified PBPK Model

Abstract

Physiologically based pharmacokinetic and absorption modeling are being used by industry and regulatory bodies to address various scientifically challenging questions. While there is high confidence in the prediction of exposure for the BCS class I drugs administered as immediate-release formulations, in the case of prolonged-release formulations, special attention should be given to the input dissolution data. Our goal was to develop and verify a PBPK model for a BCS class I compound, ropinirole, and check the biopredictiveness of the dissolution data for the prolonged-release formulation administered by Parkinson’s patients. The model was built based on quality control dissolution data reported in the certificates of analysis and verified with the use of data derived from five clinical trial reports. The simulated pharmacokinetic parameters being within a two-fold range of the observed values confirmed acceptable model performance, in vivo relevance of the in vitro dissolution profiles, and indirectly indicated ropinirole stable release from the formulation in the patients’ gastro-intestinal tract. Ropinirole PBPK model will be used for exploring potential clinical scenarios while developing a new formulation.

3D Printed Drug Delivery Systems in Action–Magnetic Resonance Imaging and Relaxometry for Monitoring Mass Transport Phenomena

“…RH is classified as a class I compound in the Biopharmaceutics Classification System (BCS). This means that at its highest therapeutic dose, RH is considered highly soluble, dissolving completely in 250 mL or less of aqueous media across the pH range of 1.2–6.8 at 37 ± 1 °C, and is also highly permeable. − The influence of the polymer and the addition of PEG 400 on matrix functional properties was determined by assessing RH release profiles, which are presented in Figure .…”

Can 3D Printed Tablets Be Bioequivalent and How to Test It: A PBPK Model Based Virtual Bioequivalence Study for Ropinirole Modified Release Tablets

“…The volume of distribution was predicted using Sawada et al 1984, an equation based on tissue-to-plasma partition coefficients predicted by the Rodgers and Rowland model [25,26]. After gaining confidence in distribution and elimination, the absorption model was extended to an Advanced Dissolution, Absorption, and Metabolism (ADAM) model to describe drug absorption from the prolonged release formulation [27]. The model was validated using concentration-time profiles for healthy volunteers (Sim-Healthy Volunteers virtual population), and subsequently for Parkinson's disease patients (Sim-North European virtual population).…”

Report on the Virtual Workshop: A Quest for Biowaiver, Including Next Generation Dissolution Characterization and Modeling

“…This disease requires precise and variable therapy, which could potentially be supported by MIPD, but there are several obstacles inhibiting implementation. These include 3D printing method standardization, high throughput quality control dissolution testing, and others (33,34). This last presentation was followed by a question-andanswer session.…”