Drying of the Glass Transition Using IsoStep - METTLER TOLEDO

Drying of the Glass Transition Using IsoStep

Introduction 

If several thermal events occur simultaneously in a DSC measurement, the problem is then how to separate the different processes involved. Often, a change in heat capacity is overlapped by exothermic or endothermic peaks, e.g. through chemical reactions, crystallization or vaporization. One possible way to separate the different processes is to vary the measurement conditions in the conventional DSC. For example, heating and cooling measurements can be performed at different rates and in different temperature ranges using different types of crucibles. This is of course relatively time-consuming.

IsoStep™ is a new technique that can be used to distinguish between such overlapping processes. It provides both the heat capacity curve and the non-reversing curve simultaneously. In this article, the separation of different thermal events is demonstrated by measuring the glass transition of a spray-dried pharmaceutical substance. The measurement of a similar compound to determine the change of heat capacity during the vaporization of water has been described in a previous article [1, 2]. As an extension of this, the relationship between the water content and the glass transition temperature is analyzed quantitatively using IsoStep™. Knowledge of this relationship is important for processing the powder because it can become sticky if the glass transition temperature is below the processing temperature.

 

 

Experimental Details

The DSC measurements were performed with a DSC822e equipped with an IntraCooler. The STARe software with the IsoStep™ option was used for the evaluation.

In the IsoStep™method, a conventional heat capacity measurement is combined with a quasi-isothermal kinetic evaluation. The temperature program consists of a series of isothermal segments and heating steps. The parameters (length of the isothermal segments, heating rate and step height in the heating step) are not restricted in any way. They can even be different during a measurement depending on the actual task or thermal event investigated.

The heat capacity as a function of temperature is obtained from the heat flow during the heating step, and the non-reversing curve from the heat flow during the isothermal step [3]. The measurements described here used temperature steps of 1 K at 2 K/min. The isothermal period at the beginning of the measurement was 30 s. The measuring cell was purged with nitrogen.

The sample used was a spray-dried pharmaceutical product consisting of two amorphous components. The water content of the starting material was analyzed by TGA/SDTA851e and found to be 6.08%. Samples of about 8 mg were sealed in 40-µl aluminum crucibles with a 50-µm hole in the lid (ME-51140832). The samples were dried each time in the DSC at 80 °C for different periods of time before measurement in order to obtain different water contents. The advantage of this procedure was that the sample did not have to be transported after drying. The small hole in the lid restricts the evaporation of the water so that drying proceeds in a defined way. The moisture content before the beginning of the measurement, wini, was determined by measuring the decrease of the water content during the storage of the crucibles with the TGA/SDTA851e [4]. Trial experiments in the DSC and TGA showed that the samples did not change chemically during the pre-drying step.

Summary

With IsoStep™, the heat capacity and the non-reversing curve can be determined simultaneously in one measurement. This allows glass transition and vaporization processes to be separated. With a spray-dried pharmaceutical substance, it has been shown that the method can be used to quantitatively determine the effect of moisture on the glass transition temperature. The measurement procedure features easy sample preparation, direct measurement and high accuracy.

Drying and Glass Transition using IsoStep™Thermal Analysis Application No. UC 165 | Application published in METTLER TOLEDO Thermal Analysis UserCom 16