**1.5 Characterization and evaluation of co-crystals**

Co-crystal characterization is an important constituent part within co-crystal research. The basic physicochemical properties of co-crystals can usually be

#### *Modification of Physicochemical Properties of Active Pharmaceutical Ingredient… DOI: http://dx.doi.org/10.5772/intechopen.110129*

characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, Raman spectroscopy, solid-state nuclear magnetic resonance spectroscopy and terahertz spectroscopy.

#### *1.5.1 Scanning calorimetry (DSC)*

In this characterization method, two specimens—one serving as a sample and the other as a reference—are each subjected to the same temperature as well as a controlledrate environment of heating or cooling. Plotting the amount of energy required to achieve a temperature difference between the two specimens that is zero leads to illuminating conclusions. Two different types of DSC are employed frequently. First up is the power compensation DSC, which keeps the two samples in various identical furnaces. By adjusting the power input, the temperature of both is brought to the same level. As a result, the energy is translated into enthalpy or heat capacity. Another type of DSC involves keeping both sample holders in the same furnace and connecting them *via* a low-resistance heat flow path. The remainder of the interpretation is unchanged. The most widely used technique for the thermal analysis of co-crystals is differential scanning calorimetry. Differential scanning calorimetry is an ideal technique for obtaining complete melting point data and additional thermal records, such as enthalpy of melting, can also be concurrently obtained. Addition to the characterization technique, DSC has presently been used as a selection tool for rapid co-crystal screening [62, 63].

#### *1.5.2 XRD*

Phase identification is used in this analytical technique to provide information on unit cell dimension. The crystalline sample and monochromatic X-ray are constructively diffracted to produce this. The cathode ray tube used to create the monochromatic ray filters and collimates the radiation to create monochromatic radiation, which is then directed at the sample. In the sample preparation scenario, the sample is finely ground to create a homogeneous sample and to analyse the average bulk composition. D-spacing analysis is performed on the sample. A set of d-spacing is produced as the sample is positioned in a random orientation. The sample is therefore examined because each mineral has a unique set of d-spacing. The sample must adhere to Bragg's law, which links the electromagnetic radiation's wavelength to the diffraction angle 2 (nλ = 2d sin θ), in order for any of this to occur. Co-crystals' solidstate structure can be determined at the atomic level using a characterization method called XRD. The issue is that it is not always possible to produce a single pharmaceutical co-crystal that is suitable for SXRD testing. PXRD is therefore used more often to confirm the formation of co-crystals [64].

#### *1.5.3 Vibrational spectroscopy (IR and Raman)*

For determining organic structure, electromagnetic radiation with frequencies between 4000 and 400 cm−1 has been one of the most powerful tools. This electromagnetic radiation is known as infrared (IR) radiation and IR spectroscopy for its use in organic chemistry. The interatomic bonds absorb the bombarded radiation. A particular chemical bond will therefore absorb various radiations at various frequencies in various environments. Thus, inferring some conclusions about the structure from their absorption data, which is provided as a spectrum, is helpful [64].
