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The stability constant for the complexes at 37 °C, assuming a 1:1 stoichiometry, calculated from the slope of the initial
straight portion of the solubility diagram, was 733 M-1 , which indicated a suitable and stable complex formation.
The ΔGtr° values indicate whether the reaction conditions are favorable or unfavorable for drug solubilization in the aqueous carrier
solution. Negative Gibbs free-energy values indicate favorable conditions. ΔGt° and ΔHt° were negative for HP–β–CD, indicating that the transfer of the drug from pure water to polymer solutions is spontaneous.
Furthermore, as the polymer concentration increases, ΔHt° decreases, which indicates that the process becomes more favorable with higher polymer concentrations.
Figure 2: Differential scanning calorimetry spectra of glipizide and inclusion complexes. COE is coevaporation, KNE is kneading,
and PM is physical mixing.
DSC studies. Figure 2 shows DSC curves obtained for pure GLZ, HP–β–CD, their PMs, and solid dispersions prepared with HP–β–CD. Pure powdered
GLZ showed a melting endotherm at 216.73 °C. A DSC scan of HP–β–CD showed a broad endotherm at 84.7 °C because of the presence
of residual moisture in HP–β–CD. DSC thermograms of PM 2:1 and kneading method 2:1 exhibits both of these endothermic peaks,
although the peak for HP–β–CD is barely discernable.
DSC thermgrams of coevaporation 2:1 showed no endothermic peak for GLZ, and the endothermic peak of HP–β–CD was appreciably
broader. This result seemed to indicate the formation of an inclusion complex.
Figure 3: Fourier transform infrared spectra of glipizide and inclusion complexes. COE is coevaporation, KNE is kneading,
and PM is physical mixing.
IR studies. To further characterize possible interactions between the drug and the polymeric carrier in the solid state, IR spectra were
recorded. Figure 3 shows the spectra of all samples. The chemical interaction between the drug and the carrier often leads
to identifiable changes in complexes' IR profiles. The spectrum of pure GLZ presented characteristic peaks 3325 and 3251 cm-1 (i.e., for the N-H asymmetric stretch), 1690 and 1650 cm-1 (i.e., for the C=O stretch), 1444 and 1332 cm-1 (i.e., for the C-N stretch), and at 1159 cm-1 (i.e., for the SO2 stretch). The authors noted the presence or absence of characteristic peaks associated with specific structural groups of
the drug molecule. The FTIR spectra revealed that the drug was entrapped in the cyclodextrin cavity.
Figure 4: Solubility study of glipizide–HP–β–CD complexes.
Solubility of complexes. The solubility of the drug was determined according to the above method. The solubility of GLZ in pure water at 25 °C was
39 µg/mL. Solid dispersions prepared by coevaporation had the highest solubility, as shown in Figure 4.
Figure 5: Wettability study of Glipizide–HP–β–CD complexes.
Wettability and in vitro drug release studies. Figure 5 shows the improvement in wettability of GLZ by physical mixing and solid dispersion with HP–β–CD. Coevaporation
2:1 showed the highest wettability in water (100%), compared with pure GLZ (23.6%) after 20 min.
Ritesh B. Patel is a lecturer in the Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Gujarat, India.
Articles by Ritesh B. Patel
Rakesh P. Patel is an associate professor in the Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Gujarat, India.
Articles by Rakesh P. Patel
Madhabhai M. Patel
Madhabhai M. Patel is a professor in the Department of Pharmaceutics, Kalol Pharmacy College, Kalol, Gujarat, India.
Articles by Madhabhai M. Patel
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