Gliclazide in Binary and Ternary Systems Improves Physicochemical Properties, Bioactivity, and Antioxidant Activity

Abstract

The poor solubility of the antidiabetic drug gliclazide (Glc) is due to its hydrophobic nature. This research is aimed at improving Glc’s solubility and drug release profile, as well as at investigating additional benefits such as bioactivity and antioxidant activity, by forming binary complexes with HPβCD at different w / w ratios (1 : 1, 1 : 2.5, 1 : 4, and 1 : 9) and ternary complexes with HPβCD and Tryp at 1 : 1 : 1, 1 : 1 : 0.27, 1 : 2.5 : 0.27, 1 : 3.6 : 3.6, 1 : 4 : 1, and 1 : 9 : 1, respectively. Complexes were prepared by the physical mixing (PM) and solvent evaporation (SE) methods. The prepared inclusion complexes were meticulously characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. To verify our findings, the inclusion complexes were evaluated by equilibrium solubility, in vitro drug release profile, kinetic models, and antidiabetic and antioxidant activities in animal models. Our results demonstrated that the solubility and drug release profile were found to be enhanced through binary as well as ternary complexes. Notably, ternary complexes with a ratio of 1 : 9 : 1 showed the highest solubility and drug release profile compared to all other preparations. Data on antioxidant activity indicated that the ternary complex had the higher total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) activity than the binary complex and Glc alone, in contrast to the diabetic group. In vivo antidiabetic activity data revealed a high percentage reduction in the blood glucose level by ternary complexes (49–52%) compared to the binary complexes (45–46%; p ≤ 0.05 ). HPβCD and Tryp provide a new platform for overcoming the challenges associated with poorly soluble Glc by providing greater complexing and solubilizing capabilities and imparting ancillary benefits to improve the drug’s antidiabetic and antioxidant activities.

Multifunctional Pomegranate Peel Microparticles with Health-Promoting Effects for the Sustainable Development of Novel Nutraceuticals and Pharmaceuticals

“…The formation of supramolecular structures with CDs, which are stabilised via noncovalent bonds, provided an additional benefit by protecting bioactives against rapid oxidation by free radicals [ 69 ]. The literature also shows that HP- β -CD could act as a secondary antioxidant and, therefore, increase the system’s natural antioxidant capacity [ 70 , 71 ].…”

Formulation of Silymarin-β Cyclodextrin-TPGS Inclusion Complex: Physicochemical Characterization, Molecular Docking, and Cell Viability Assessment against Breast Cancer Cell Lines

“…According to recent reports, using a ternary system with a drug, CD, and a third auxiliary material can both lower the CD content and improve the complexation effectiveness. , There are numerous ternary substances used to prepare and evaluate inclusion complexes of poorly soluble drugs. − A novel highly water-soluble lipid-based nonionic surfactant approved as a safe excipient by the USFDA is TPGS (Figure C). It also has P-gp inhibitory effects and is well known to improve the solubility and bioavailability of drugs that are insoluble in water. , There is currently no literature describing the application of TPGS as a ternary substance in the formulation of inclusion complex of SIL with CD.…”

“… 25 , 26 There are numerous ternary substances used to prepare and evaluate inclusion complexes of poorly soluble drugs. 30 − 32 A novel highly water-soluble lipid-based nonionic surfactant approved as a safe excipient by the USFDA is TPGS ( Figure 1 C). It also has P-gp inhibitory effects and is well known to improve the solubility and bioavailability of drugs that are insoluble in water.…”