SYSTAG Automation: “Easy accessibility” solution for determining MSZ of product solvent mixture

SYSTAG Automation: “Easy accessibility” solution for determining MSZ of product solvent mixture

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Products & Services | SYSTAG, System Technik AG


SYSTAG Automation has added a proven solution for determination of the metastable zone (MSZ) of a product solvent mixture to its ‘Easy Accessibility’ portfolio.

The solution enhances the efficiency of laboratory work in the general process of development for R&D purposes, as well as in particular in EPR-Operations (Established Parameter Ranges), stress tests and DoE (design of Experiments).

The solution is reproducible and yet individual, with independent and complete recorded test series to determine and interpret the metastable zones of a product solvent mixture.

It avoids sated range of product concentration, with associated risk of spontaneous crystallization, along with significant problems, like a loss of yield etc.

Hardware Setup

The solution is based on twin parallel reactors, both 250ml size, with two gravimetric feeds on each reactor unit.

The reactors use individual temperature control with pH-Sensor and turbidity sensor.

The process is driven by SYSTAG Automation FlexyCUBE with Recipe Task for 24h operation with on-line trend for data visualization.

Proof of concept

The solution was proved by two individual teams, to ensure reproducibility. Each team consisted of a Chemist and Chemical Engineer.

The teams performed 25 experiments apiece, both in manual mode and in recipe mode.

Solution design

The experiments included individual heating and cooling cycles, programmed by recipe software.

They included automatic dosing of Isopropyl Acetate (IPAc) to achieve different concentrations.

Turbidity sensors were used to detect the start of crystallization and measure solubility at different temperatures and different concentrations.


The 25 experiments demonstrated that the original process and distillation was carried out very close to the border of the meta stable zone (solubility limit) in which spontaneous crystallization might occur at any time.

Knowledge gained included high risk of loss of yield, quality and time by spontaneous crystallization during scale-up or production.

The concentration of the process was modified to avoid risk of spontaneous crystallization at any time.

The knowledge of the MSZ is essential for crystallizations to achieve a fast and successful scale up, allowing more robust processes to be achieved.


Both teams found determination of the data very easy, using FlexyCUBE in connection with the turbidity probe.

It was further found that preparation of recipes took about 30 minutes and the preparation of the experiment a further 30 minutes.

With experiments running 24 hours a day, there was almost a three-factor time saving compared to conventional reaction methods, with additional (and even higher) savings in time required to collect, display and evaluate all the data.


Click on SYSTAG Automation: MSZ determination solution for other information.
Click on SYSTAG to contact the company directly.

Twin reactor set up

Twin reactor set up

Result of original process

Result of original process

Result of modified process

Result of modified process

Supplier Information
Supplier: SYSTAG, System Technik AG
Address: Bahnhofstrasse 76, CH-8803 Rüschlikon, Switzerland
Tel: +41 (0)44 704 54 54
Fax: +41 (0)44 704 54 55

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