4.

1 Attenuated Total Reflectance

The ATR accessories, Germanium crystal with a high refractive index is suitable for the FTIR ATR analysis of traditionally difficult samples that require controlled penetration of the infrared beam. The shallow depth of penetration of the Germanium ATR allows the analysis with no band distortion to overcome the often difficult quantitative analysis of strongly infrared absorbing materials [31].

A molecule of paracetamol (Figure 4.1) has a proton-donor NH-group, a proton-acceptor C=O-group, whereas the OH-group can act simultaneously as a proton-donor and a proton-accepter. In the crystalline state, the molecules of paracetamol are linked by NHO and OHO hydrogen bonds into chains. By using ATR-IR, it can detect the interaction between the Paracetamol and P407.

Figure 4.1 Structure of PA (left) and P407 (right) Table 4.1 AT-IR results Funtional Group / Sample PA P407 A : P (1:1) F : M (1:1) B : P (1:3) G : M (1:3) C : P (1:5) H : M (1:5) D : P (3:1) J : M (3:1) E: P (5:1) I : M (5:1) 3323.1 3529.9 3323.1 3322.9 3323.8 3317.3 3323.8 3457.9 3322.4 3323.4 3323.3 3323.0 1650.1 1651.4 1651.9 1651.5 1653.8 1651.2 1651.0 1661.7 1651.5 1650.9 1651.4 1651.7 1563.6 1562.2 1563.1 1561.5 1562.2 1562.9 1565.0 1563.7 1563.0 1563.4 1562.8 1104.9 1107.5 1107.3 1106.5 1106.7 1106.3 1106.4 1105.7 1105.0 1108.0 1103.7 -OH (cm )
-1

C=O (cm )
-1

C-N-C (cm )
-1

C-O (cm-1)

Absence or shifting or broadening of characteristic peaks in IR spectrum on both solid dispersion techniques indicate changes in the drug characteristic or possibilities of PA and P407 interactions. The appearance of all peaks in Table 4.1 confirmed the presence of hydroxyl group, amide group and ether group in both solid dispersion technique [29].

Alcohol groups will show strong and broad hydrogen bonded OH stretching bands centered between 3400 and 3300 cm-1. Parcetamol contain alcohol group and it has appeared at peak 3323.1 cm-1 and for P407 it has appeared at 3529.9 cm-1. The impact of hydrogen bonding is to produce signicant band broadening and to lower the mean absorption frequency. The lowering of the frequency tends to be a function of the degree and strength of the hydrogen bonding. The hydrogen bonding weakens the OH bond by shifting the band to lower frequency. The peak for melting technique (1:3) has shifted to lower frequency 3317.3 cm-1 indicates that there is weak hydrogen bonding occur. While for melting technique (1:5) OH peak differ from the pure PA because the existence of P407 are much stronger than PA. It tends to shift to higher frequency 3457.9 cm-1 close to OH peak for P407 3529.9 cm-1[32] [33].

Since Paracetamol structure consist of secondary amide, it have broad C=O absorption in the range from 1680 to 1630 cm-1. Overlapping bands at that range which indicates that C=O band partially overlapped with N-H bending

band. However, secondary amide gives relatively strong bending bands at about 1550 cm-1. These are attributed to a combination of a C-N stretching band and an N-H bending band [32]. The peak of C=O and C=N bond for melting technique (1:5) has also shifted to higher frequency 1661.7 cm-1 and 1565.0 cm-1 respectively.

On the other hand, C-O stretching has appears in all spectra indicates present of P407 in the sample mixture. This is support by the new peaks shown in both techniques at 2884 cm-1 as it does not appear in pure PA and only exist in P407. However, all ratio in physical technique revealed no considerable interaction between PA and P407 as the position of corresponding bands were similar as in pure PA. So as in melt technique at ratio 1:1, 3:1 and 5:1 shows no considerable interaction. The compounds exist as individual characteristic at the surface. No hydrogen bond has been justified.