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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Medicinal Chemistry

Background:

• Gliclazide (Glc) exhibits poor solubility due to its hydrophobic nature, limiting its therapeutic efficacy.
• Developing strategies to enhance Glc solubility and bioavailability is crucial for effective antidiabetic treatment.

Purpose of the Study:

• To improve the solubility and drug release profile of gliclazide (Glc).
• To investigate the potential of binary and ternary complexes involving HPβCD and tryptophan (Tryp) for enhanced bioactivity and antioxidant properties.
• To evaluate the antidiabetic and antioxidant effects of these complexes in animal models.

Main Methods:

• Binary and ternary inclusion complexes of Glc with HPβCD and Tryp were prepared using physical mixing and solvent evaporation methods.
• Characterization involved X-ray diffractometry (XRD), scanning electron microscopy (SEM), and ATR-FTIR spectroscopy.
• Evaluations included equilibrium solubility, in vitro drug release, kinetic modeling, and in vivo antidiabetic and antioxidant activity assessments.

Main Results:

• Both binary and ternary complexes significantly enhanced Glc solubility and drug release.
• Ternary complexes, particularly at a 1:9:1 ratio of Glc:HPβCD:Tryp, exhibited the highest solubility and release rates.
• Ternary complexes demonstrated superior antioxidant activity (increased TAS, SOD, CAT) and a greater reduction in blood glucose levels (49-52%) compared to binary complexes (45-46%) in vivo.

Conclusions:

• HPβCD and Tryp form effective complexes with Glc, overcoming its poor solubility challenges.
• Ternary complexation provides enhanced solubilization and drug release, along with improved antidiabetic and antioxidant activities.
• This approach offers a promising strategy for developing more effective gliclazide formulations.