Development of an Osmotically Controlled Drug-Delivery System of Glipizide - Pharmaceutical Technology

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Development of an Osmotically Controlled Drug-Delivery System of Glipizide
The authors describe the development of an inclusion complex of GLZ and formulated an extended-release dosage form based on osmotic technology.


Pharmaceutical Technology
pp. 80-91

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 ΔGt r 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 g/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.


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