**Table 4.**

**141**

**Figure 7.**

*Studies on Histamine H2-Receptor Antagonists by Using Density Functional Theory*

Comparing the global descriptive parameters of histamine H2 receptor antagonist, nizatidine is found to be having higher softness, ionization potential, electron affinity, chemical potential and lower hardness, which shows that nizatidine is less stable and chemically more reactive. A higher value of electrophilicity index indicates its high biological activity. In case of stability reactivity and biological activity, ranitidine comes next to nizatidine and among them, cimetidine is more stable and

The theoretical studies revealed that nizatidine is highly stable and biological active molecule among the four histamine H2 receptor antagonists. But the value of Gibbs free energy emphasis that the solubility of nizatidine is less. The possible solution to enhance the solubility and bioavailability of the pharmaceutical drug is amorphisation of its crystalline counterpart. We have already reported the molecular dynamics of nizatidine in its glassy and supercooled liquid state using broadband dielectric spectroscopy [21]. The dielectric measurements of nizatidine were performed from 123.15 K to 373.15 K by quench cooling the sample. However, the sample does not crystallize during cooling from the melting temperature. Then the measured dielectric loss spectra (i.e., imaginary part of dielectric permittivity

The dielectric measurements revealed that the sample nizatidine is a good glass former with glass transition temperature Tg around 282.09 K with steepness index 91 without showing any recrystalisation tendency during heating and cooling. The steepness index is the measure of the non-Arrhenius character of the temperature dependence of the α-relaxation times. In contrast to strong liquids (m = 16), fragile glass-forming materials (m = 200) show a fast change in its viscosity (relaxation time) as it approaches the glass transition temperature. The knowledge whether a glass former is strong or fragile seems to be essential in case of choosing the best temperature condition for storing an amorphous pharmaceutical where the structural relaxation

ε" plotted as a function of frequency f) are shown **Figure 7**.

*Dielectric loss curves obtained for nizatidine in the supercooled liquid state [21].*

*DOI: http://dx.doi.org/10.5772/intechopen.95322*

having lower biological activity.

**3.6 Molecular dynamics**

*Global descriptors of studied compounds using DFT/B3LYP/6-31 + G (d) level of theory.*

Comparing the global descriptive parameters of histamine H2 receptor antagonist, nizatidine is found to be having higher softness, ionization potential, electron affinity, chemical potential and lower hardness, which shows that nizatidine is less stable and chemically more reactive. A higher value of electrophilicity index indicates its high biological activity. In case of stability reactivity and biological activity, ranitidine comes next to nizatidine and among them, cimetidine is more stable and having lower biological activity.
