Results and discussion
The phase-solubility diagram obtained was classified as AL type because the apparent solubility of nabumetone increased linearly (R2 5 0.968) with β-CD concentration over the entire concentration range studied, thereby suggesting the formation of a water
soluble complex. A slope value of less than 1.00 indicated that an inclusion complex in a molar stiochiometric ratio of 1:1
was formed between the drug and β-CD in solution. The stability constant (411.76 M–1), computed from the slope and intercept of the phase solubility diagram, indicated considerable interaction between the hydrophobic
drug and the hydrophobic cavity of β-CD. The values of stability constants described in the literature ranged from 100 to
20,000 M–1 for drug β-CD complexes (22).
The IR spectra of the drug, β-CD, and the kneaded complex are portrayed in Figure 1. The IR spectra of the complex revealed
that many functional groups of the drug might have interacted with β-CD. A low-intensity peak assignable to the drug carbonyl
stretching appeared to have shifted from 1705 cm–1 to 1690 cm–1 in the spectra of the kneaded complex. This displacement and reduction of the peak intensity suggested the possibility of
the hydrogen-bond formation between the -C=O of the guest molecule and the hydroxyl functional group of β-CD. The spectra
of the complex showed that the broad β-CD band between 3900 and 2900 cm–1 overlapped the drug characteristic peaks as a result of -CH- aromatic stretching and -CH- aliphatic stretching of the same
region. A similar overlapping of the drug characteristic peaks by the β-CD band on complexation has been published (23).
Figure 1: FTIR spectra of (a) nabumetone, (b) b-cyclodextrin, (c) physical mixture, and (d) kneaded complex. All figures
are courtesy of the authors.
The drug peaks at 1645 cm–1 resulting from skeletal vibrations of -C=C- bonds in the aromatic ring decreased in the intensities in the spectra of the
complex, thereby indicating considerable drug and β-CD interaction. These spectral observations suggest that the vibration
and bending of the drug molecule might be restricted because of complexation as the aromatic ring of the drug was inserted
in the β-CD cavity.
Differential scanning calorimetry..
The endothermic peak at 80 °C in the DSC scan of the drug represented the melting-point transition of the crystalline drug
(see Figure 2). The broad band that appeared between 110 °C and 140 °C in the thermogram of β-CD can be attributed to a loss
of water or a molecular dehydration process. The reduced area of the drug endothermic peak in the DSC spectra of the complex
indicated considerable interaction between the drug and β-CD, which substantially reduced the drug crystallinity. This reduction
in the band area and the peak intensity indicates a reduction in the energy required for the melting transition. The β-CD
dehydration band in the DSC scan of the kneaded product shifted to lower temperature between 90 and 130 °C. A similar shift
in the β-CD dehydration band on complexation has been recorded (23).
Figure 2: DSC thermogram of (a) nabumetone, (b) b-cyclodextrin, (c) physical mixture, and (d) kneaded complex. All figures
are courtesy of the authors.