ADMET and DMPK, Vol. 14 , 2026.
Original scientific paper
https://doi.org/10.5599/admet.3136
Novel stirring method for small-scale dissolution test: Rotating vessel method
Shiori Ishida
; Molecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan
Samuel Lee
; Pion Inc. (UK) Ltd. Forest Row Business Park, Station Road, East Sussex, RH18 5DW, United Kingdom
Balint Sinko
orcid.org/0009-0005-8256-4348
; Pion Inc. (UK) Ltd. Forest Row Business Park, Station Road, East Sussex, RH18 5DW, United Kingdom
Karl Box
; Pion Inc. (UK) Ltd. Forest Row Business Park, Station Road, East Sussex, RH18 5DW, United Kingdom
Kiyohiko Sugano
orcid.org/0000-0001-5652-1786
; Molecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan
*
* Corresponding author.
Abstract
Background and purpose: In the compendial dissolution test, the overhead rotating paddle method (ORP) has been used for stirring, whereas the magnetic stirring bar method (MSB) has been employed for small-scale dissolution tests, such as the μDISS ProfilerTM (μDISS). Previous reports have indicated that differences exist in the precipitation profiles of a drug between ORP and MSB, because the latter causes contact-induced nucleation. However, it has been difficult to use an ORP and an in situ UV probe simultaneously in μDISS. In this study, a novel stirring method, the rotating vessel method (RV), was developed for μDISS. The dissolution and precipitation profiles of model drugs in RV-μDISS were then compared with those in MSB-μDISS, as well as with the results of conventional dissolution tests using an ORP. Experimental approach: In RV-μDISS, a small paddle (approximately 1/4 of the conventional paddle) was fixed to the UV probe, and the glass vessel was rotated to produce a flow pattern similar to that of ORP. The dissolution and bulk-phase precipitation tests were performed for ibuprofen sodium (IBU Na) and carbamazepine (CBZ), respectively, using RV-μDISS and MSB-μDISS, as well as ORP with the conventional vessel (500 mL, for IBU Na) (CV) or the mini-vessel (50 mL, for CBZ) (MV). Key results: The dissolution rate of IBU Na was similar in all methods. Rapid precipitation of crystalline IBU free acid was observed in the MSB-μDISS method. In contrast, no crystalline precipitation was observed in RV-μDISS and ORP-CV, and the drug phase-separated as a liquid (oil) phase (liquid-liquid phase separation). The precipitation rate of CBZ in RV-μDISS was similar to that in ORP-MV, but slower than that in MSB-μDISS. Conclusion: The precipitation profile in RV-μDISS was close to those in ORP-CV and ORP-MV. RV-μDISS would be a useful tool for the assessment of the precipitation profiles of drugs.
Keywords
Hydrodynamics; precipitation; magnetic stirrer; ibuprofen; carbamazepine
Hrčak ID:
345188
URI
Publication date:
11.1.2026.
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