**3.6 Molecular dynamics**

*Drug Design - Novel Advances in the Omics Field and Applications*

**140**

**Sample** Nizatidine Cimetidine Famotidine

Ranitidine

**Table 4.**

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

**IP (Ionization** 

**EA (Electron** 

χ **(Electronegativity)**

μ **(Chemical** 

ω **(Electrophilicity** 

η **(Hardness)**

**S (Softness)**

**index)**

3.387

1.91 2.348 3.051

2.279 2.789 2.399 2.338

0.214

0.208

0.179

0.219

**potential)**

−3.929 −3.264 −3.356 −3.776

**affinity)**

1.65 0.475 0.957 1.439

3.929 3.264 3.356 3.776

**potential)**

6.209 6.052 5.755 6.114

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

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

**Figure 7.** *Dielectric loss curves obtained for nizatidine in the supercooled liquid state [21].*

is closely connected to crystallization process [22]. And it is found that nizatidine is stable over the measured temperature range up to 307.15 K. Of course, the dielectric studies is only giving an indication on the molecular mobility, for detailed information regarding the molecular mobility of nizatidine in glassy and supercooled liquid state refer paper published by Sailaja et al. [21].
