# Novel stirring method for small-scale dissolution test: Rotating vessel method

## TL;DR

A new stirring method called rotating vessel (RV) was developed for small-scale drug dissolution tests, showing similar results to traditional methods and avoiding unwanted drug precipitation.

## Contribution

The novel rotating vessel method enables small-scale dissolution testing with flow patterns similar to conventional methods while avoiding contact-induced nucleation.

## Key findings

- The dissolution rate of ibuprofen sodium was similar across all methods.
- RV-μDISS avoided crystalline precipitation seen in MSB-μDISS for ibuprofen free acid.
- RV-μDISS produced precipitation rates for carbamazepine similar to conventional ORP methods.

## Abstract

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.

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).

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.

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.