Glimepiride/hydroxypropyl-β-cyclodextrin inclusion compound: preparation, characterization, and evaluation.

Objective: To enhance solubility and bioavailability of GM, an inclusion compound of glimepiride/hydroxypropyl-β-cyclodextrin (GM/HP-β-CD) was prepared using mechanical ball milling.

Significance: Based on response surface optimization for the ball milling preparation of the inclusion compound, this study investigates its in vitro and in vivo release and pharmacokinetics.

Methods: GM/HP-β-CD inclusion compound was prepared by optimized ball milling based on response surface methodology and characterized using powder x-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy, and the stability of the compound was studied. In addition, GM/HP-β-CD inclusion compound's in vitro release and in vivo release assays were performed.

Results: Optimal ball milling conditions for a 1:1 molar ratio of GM/HP-β-CD were a milling speed of 296 rpm, a milling time of 88 min, and a filling rate of 17.7%. Solubility and dissolution rate experiments indicated that the solubility of the GM/HP-β-CD inclusion compound was 20 times higher than that of GM, and the dissolution rate was 12.7 times faster. Additionally, the thermal stability and photostability of the inclusion compound were improved. In vivo pharmacokinetics and pharmacodynamics studies showed that, compared to GM, the GM/HP-β-CD inclusion compound shortened the T_max by 1 h, increased the maximum plasma concentration by nearly 3.5 times, and significantly enhanced bioavailability.

Conclusion: GM/HP-β-CD inclusion compound demonstrates potential for developing sustained-release formulations, thereby prolonging the hypoglycemic effect of GM, reducing dosing frequency, and improving patient compliance with oral administration.