ATR-FTIR studies of HME preparation

It is worth emphasizing at this point that PCM was chosen as an interactive API due to the availability of proton donor in its chemical structure. Whereas, CAF is chosen as a non-interactive API as there is no proton donor available in its chemical structure for the interaction with proton acceptor of PVP monomer. This could be further confirmed from ATR-FTIR study of the prepared samples.

3.3.3.3.1. ATR-FTIR studies of HME PCM - PVP K29-32

Figure 3.20 shows the ATR-FTIR spectra of pure PCM, PVP, PM and HME of 20-70% PCM PVP K29-32.

Figure 3.20: ATR-FTIR spectra of PM and HME PCM-PVP K29-32 a) Form I PCM, b) raw PVP K29-32, c) PM 50% PCM and PVP K29-32, d) HME 20% PCM-PVP K29-32, e) HME 30% PCM-PVP K29-32, f) HME 40%

PCM-PVP K29-32, g) HME 50% PCM-PVP K29-32, h) HME 60% PCM-PVP K 29-32, i) HME 70% PCM-PVP K29-32

Carbonyl (C=O) group of PVP monomer reveals stretching at 1652 cm^-1. After the HME processing of PVP K29-32 with PCM, this band was slightly shifted to the lower frequency i.e.

1647 cm^-1. This indicated a certain extent of interaction that occurred at the carbonyl group of PVP monomer.

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The ATR-FTIR spectrum of crystalline PCM indicates a characteristic band at 3324 cm^-1 which is attributed to the NH stretching of PCM. This band was broadened in HME product which suggested the weakening or disappearing of the original –NH stretching vibration. Furthermore, the –OH stretching band of crystalline PCM at region 3100 cm ^-1 was also broadened in the HME PCM PVP K29-32 products as compared to its pure crystalline ATR-FTIR spectrum which shows a moderate stretching band. Both changes of the characteristic peaks in the regions of 3100 cm^-1 and 3324 cm^-1 indicated different vibration mode of -NH and –OH in the HME PVP-based SD. This might be due to the breaking of intermolecular hydrogen bonds of the crystalline PCM that dissolves into the polymer carrier while HME processing.

At the fingerprint region of circa 900-700 cm^-1, triplet peaks were seen for pure PCM and PM 50%

PCM-PVP K29-32. However, in HME products, only a doublet was seen. According to Qi et al.

(2008), the triplet peaks in this region was attributed to the crystalline material of PCM, whereas a doublet peaks infer amorphousness of the PCM. Therefore, based on the ATR FTIR spectra in Figure 3.20, HME 10% to 50% PCM PVP K29-32 extrudates were amorphous in nature as shown by the double band in print region of 900-700 cm^-1. At higher PCM loading of HME PVP-based (60% and 70%) SD, the ATR-FTIR spectra show the reappearance of the diagnostic peaks of crystalline PCM (3100, 3324 and 807 cm^-1) which implies the minor crystal trace in these samples.

This result is in agreement to the MTDSC thermograms as presented in Figure 3.11.

Combining the observations of down-shifted carbonyl stretching band in PVP monomer and the broadening in –NH/-OH stretching band of PCM molecules, it was thus suggested that hydrogen bond interactions were formed between the C=O group of PVP monomer and NH or OH groups of PCM (Nair et al., 2001, Wang et al., 2002). Attributions of each band from the spectra of HME products are further detailed in Table 3.9.

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Table 3.9: Infrared bands of hot melt extrudate of PCM PVP in comparison to the corresponding PM

Wavenumber (cm^-1)

Attribution in pure PCM (Wang et al., 2002)

Changes observed in HME extrudates

3324 NH stretching vibration Broadening of the band indicated stretching of -NH via intermolecular hydrogen bond within the crystal disappears, i.e. irregularity induced by incorporation of PVP or dissolved PCM molecules.

3126 H-OH/OH stretching vibration plus combination band

The glassy state of HME products causes slight shift in this band to higher wave-number which representing the solidified state of solid solution

3174 H-OH/OH This band is till observed due to intra and intermolecular hydrogen bond with polymer molecules

1650 C=O stretching vibration The glassy state of HME products causes slight shift in this band to lower frequency representing the hydrogen bond interaction

1560 NH in plane bending It reduced intensity, shifted to lower frequency due to intermolecular hydrogen breaking in PCM crystal thus indicated amorphous formation

1609, 1504, 1433

Aromatic mode 1512-shift to higher wavenumber due to solid solution form

1374 CH bend Higher peak relatively to aromatic mode

1328 OH bending vibration Shifted to lower wavenumber indicated stronger hydrogen bond interaction

1226-1259 C-O/C-N stretching vibration

broaden and higher frequency due to dispersive within polymer and amorphous have weaker bonds than crystal

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3.3.3.3.2. ATR-FTIR studies of HME PCM in PVPVA 6:4

Figure 3.21 shows the ATR-FTIR spectra of pure PCM, PVPVA 6:4 and HME PCM-PVPVA 6:4 systems. According to Figure 3.21 (b), ATR-FTIR spectra of PVPVA 6:4 indicates two peaks at

Figure 3.21: ATR-FTIR spectra of PCM, PVPVA 6:4 and HME PCM-PVPVA 6:4 systems

Interestingly, it is found that the C=O stretching (1734 cm^-1) of the VA moiety in both PM and HME preparations of binary PCM-PVPVA 6:4 did not shift in comparison to the spectra of PVPVA 6:4 alone. This is in contrast to the C=O stretching of pyrrolidone where down-shifting of its peak position (from 1667 cm^-1 to 1656 cm^-1) was noted in HME PCM-PVPVA 6:4 in comparison to the PM and raw PVPVA 6:4. Therefore it was believed that the main interactions between PCM and PVPVA 6:4 occurs preferentially at the C=O group of the pyrrole group rather than the C=O in vinyl-acetate group. On that basis, the intensity of PCM-polymer interaction was higher in PVP K29-32 carrier system than in HME PVPVA 6:4 system.

3.3.3.3.3. ATR-FTIR studies of HME CAF-PVP K29-32 and PVPVA 6:4

Figure 3.22 compares the ATR-FTIR spectra of CAF, PVP 32 and HME CAF in PVP K29-32. ATR-FTIR spectra of HME 10-20% CAF in PVP K29-32 did not show any significant peak

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(Figure 3.22). This was attributed to the absence of physical interactions between the CAF and PVP (PVP K29-32 and PVPVA 6:4) molecules.

Figure 3.22: FTIR spectra for a) CAF, b) PVP K29-32, c) PM 10% CAF-PVP K 29-32, d) HME 10% CAF-PVP K29-32, e) HME 20% CAF-PVP K29-32

Figure 3.23 shows the ATR-FTIR spectra of CAF, PVPVA 6:4 and HME CAF-PVPVA 6:4.

Similarly, no significant peak shift is noted in the PM and HME of CAF-PVPVA 6:4 which reconfirms the lack of drug-polymer interaction in these systems.

Figure 3.23: ATR-FTIR spectra for a) CAF, b) PVP VA 6:4, c) PM 10% PVPVA 6:4, d) HME 10% CAF-PVPVA 6:4 e) HME 20% CAF-CAF-PVPVA 6:4

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