Reference pan

The reference pan should always be of the same type as the sample pan. Ideally, the mass of the reference pan should be close to the mass of the sample pan and sample. This will minimize the start-up hook observed at the beginning of the DSC experiment (see Subsection 2.4.1). To compensate for the sample mass, one or two extra aluminum sample pan lids may be added to the reference pan. 

Once a pan has been sealed, it is difficult to know if it contains a sample or not. It is recommended that a small mark may be scratched on the lid of any empty reference pan in order that it may be easily identified. It can be very costly to discard perfectly good gold or platinum reference pans just because one cannot see inside them. 

FIGURE 2.6 Summary of typical DSC pan configurations used in pharmaceutical DSC 

---

General References Pan N. Garay, P. E., Tump Application Desk Book,... 

Weigh out either 10 mg of glass beads or A1203 into the reference pan or just use an empty reference pan [9]. 

The differential scanning calorimeter (DSC) works on a technique that detects physicochemical transition in a system by measuring the amount of heat absorbed or released as the sample is heat across its suspected transition range. The heat absorbed or released from a sample of known mass compared with that of an empty reference pan. Modulated differential scanning calorimeter (mDSC) works on an advanced technology version of DSC, where the signal quality has been improved using... 

Specific heat, Cp, is one of the many material properties that can be measured with DSC. During a DSC temperature sweep, the sample pan and the reference pan are maintained at the same temperature. This allows the measurement of the differential energy required... 

These devices have a disk (e.g. constantan alloy) on which the sample and reference pans rest on symmetrically placed platforms. Thermocouple wire (e g. chromel alloy) Is welded to the underside of each platform. The chromel-constantan junctions make up the differential thermocouple junctions with the constantan disk acting as one leg of the thermocouple pair. 

The reference material (e.g., sapphire or A1203) is placed in the reference pan which is placed in the reference holder, and scanning from T, to Tc is carried out to obtain curve IV. 

A DuPont Model 990 thermal analyzer equipped with a Model 910 DSC cell base was used for differential scanning calorimetry. Samples were analyzed as 15 (w/w) solutions of freeze-dried RDP which had been dialyzed to remove excess buffer salts. A heating rate of 5°C/min was used runs were performed in a nitrogen atmosphere (5 psi). A known weight of water was used in the reference pan to balance the heat capacity of the sample pan. 

Two principal DSC designs are commercially available—power compensated DSC and heat flux DSC. The two instruments provide the same information but are fundamentally different. Power-compensated DSCs heat the sample and reference material in separate furnaces while their temperatures are kept equal to one another (Fig. IB). The difference in power required to compensate for equal temperature readings in both sample and reference pans are recorded as a function of sample temperature. Heat flux DSCs measure the difference in heat flow into the sample and reference, as the temperature is changed. The differential heat flow to the sample and reference is monitored by chromel/ constantan area thermocouples (Fig. IC). ... 

Accurate heat capacity, Cp, measurements may be obtained by DSC under strict experimental conditions, which include the use of calibration standards of known heat capacity, such as sapphire, slow accurate heating rates (0.5-2.0 K/min), and similar sample and reference pan weights. MDSC or DDSC also have been used to determine the heat capacity of several pharmaceutical materials. ... 

The principle of DSC is as follows two ovens are linearily heated one oven contains the sample in a pan, the other contains an empty pan as a reference pan. If no change occurs in the sample during heating, the sample pan and the reference pan are at the same temperature. If a change such as melting occurs in the sample, energy is used by the sample and the temperature remains constant in the sample pan while the temperature of the reference pan continues to increase. Therefore a difference of temperature occurs between the sample pan and reference pan. 

There are several different types of instrument covered under the term DSC, which have evolved from differential thermal analysis (DTA) and measure the temperature difference between sample and reference pans located in the same furnace. This is then converted to heat flow using a calibration factor. A detailed analysis of DSC requires consideration of the various sources of heat loss, and these are generally captured in the calibration routine for the instrument. Absolute temperature calibration is achieved through the use of pure indium (156.6 °C) and tin (231.9 °C) melting-point standards. A comprehensive analysis of the theory of DSC contrasted with DTA may be found in several reference works (Richardson, 1989, Gallagher, 1997). 

In the case of DTA, an inert material is placed in the reference pan such that the heat capacity of the sample is approximately matched. Under these conditions, when the sample and reference are being heated at a constant rate, the DTA signal will be small when no transition is occurring. Ideally, the arrangement of the pans in the furnace is exactly symmetrical so when the heat capacity of sample and reference are exactly the same, the temperature difference is zero. 

In a typical DSC experiment, a weighed sample is encapsulated in an aluminum pan. This is then placed into the DSC together with a reference pan. The sample and reference are then heated in a controlled environment, and the heat flow difference between them is recorded. Similar experiments are made with standard materials in order to obtain calibration constants so that quantitative temperature and heat flow data may be obtained in subsequent experiments. The variables and issues arising from this simple description of a typical DSC experiment can be split into three categories equipment, sample, and experiment. These areas are described in more detail later. 

The magnitude of start-up hook can be minimized by matching the mass of sample and reference pans. Figure 2.8 shows the heat flow data for a series of experiments on a pharmaceutical material where the reference mass has been... 

FIGURE 2.8 Comparison of several DSC heat flow curves for a potential drug candidate. No reference pan reference pan matched to sample pan weight matched reference pan mass plus an additional aluminum lid matched reference pan plus two additional aluminum lids. All runs are at 10°C/min. Nitrogen purge gas at 10 ml/min. 

In Figure 4 above, a small feature is observed in the experimental data near the onset of reaction. The magnitude of this feature varied from run to run and is attributed to two factors, unbalance between illumination on the sample and reference pans in the DSC and an exotherm associated with the initiator production reaction between the sensitizer and activator. It is not veiy reproducable but is most probably an extremely fast reaction temporally unresolved by the instrumentation. 

---