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Novel stirring method for small-scale dissolution test: Rotating vessel method
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DOI：10.5599/admet.3136.png)
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Abstract
En 中文
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 & micro;DISS ProfilerTM (& micro;DISS). 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 & micro;DISS. In this study, a novel stirring method, the rotating vessel method (RV), was developed for & micro;DISS. The dissolution and precipitation profiles of model drugs in RV-& micro;DISS were then compared with those in MSB-& micro;DISS, as well as with the results of conventional dissolution tests using an ORP. Experimental approach: In RV-& micro;DISS, 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-& micro;DISS and MSB-& micro;DISS, 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-& micro;DISS method. In contrast, no crystalline precipitation was observed in RV-& micro;DISS and ORP-CV, and the drug phase-separated as a liquid (oil) phase (liquid-liquid phase separation). The precipitation rate of CBZ in RV-& micro;DISS was similar to that in ORP-MV, but slower than that in MSB-& micro;DISS. Conclusion: The precipitation profile in RV-& micro;DISS was close to those in ORP-CV and ORP-MV. RV-& micro;DISS would be a useful tool for the assessment of the precipitation profiles of drugs. (c) 2026 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
Keywords:
Hydrodynamics
precipitation
magnetic stirrer
ibuprofen
carbamazepine