Pharmacodynamic assessment of gliclazide multiparticulate system | ||
| Egyptian Pharmaceutical Journal | ||
| Volume 21, Issue 4, October 2022, Pages 411-423 PDF (3.91 M) | ||
| DOI: 10.4103/epj.epj_46_22 | ||
| Authors | ||
| Aya R. Abdou; Nesrin F. Taha; Ahmed A. El-Ashmawy; Ebtesam W. Elsayed; Khaled M. Mahmoud; Laila H. Emara | ||
| Abstract | ||
| Background Conventional dosage forms of oral hypoglycemic drugs, including gliclazide (GLZ), may have a number of limitations, reducing their bioavailability. Thus, efforts are directed to design novel modified-release (MR) dosage forms for these drugs. The possible role of orally administered GLZ-MR multiparticulates in the treatment of hyperglycemia as well as improvement of impaired wound healing associated with type 2 diabetes mellitus was investigated. Objective This study aimed to evaluate the pharmacodynamics (PD) of GLZ-MR multiparticulate system against Diamicron MR tablets in nondiabetic (healthy) and streptozotocin-induced diabetic rats, by measuring blood glucose levels. For the first time, the hypothetical wound-healing capabilities of multiple doses of both treatments in diabetic rats were also studied by evaluating the wound diameter and histology. Materials and methods Novel cross-linked freeze-dried GLZ-alginate-gelatin beads were prepared. Two GLZ treatments at 4 mg/kg [test (T, MR beads) and reference (R, Diamicron MR 30 mg)] were administered to rats. A single-dose PD study was carried out on both healthy and diabetic rats, whereas the multiple-dose study was evaluated in diabetic rats. A single-dose pharmacokinetics (PK) study was conducted for assessment of the PK-PD relationship in healthy rats. Results and conclusion The single-dose study on nondiabetic rats showed that T beads exhibited a greater magnitude of blood glucose level reduction, with 1.5-fold increase in C, compared with R. A direct linear relationship with high correlation was detected between GLZ glucose-lowering effect and its PK parameters, only for T beads. Multiple dosing of T beads was more efficient than R in managing hyperglycemia of wounded diabetic rats. T beads allowed almost complete wound closure, after multiple dosing for 17 days. The proposed GLZ beads could provide a promising therapeutic prospect for managing hyperglycemia as well as resolving impairment of wound healing associated with diabetes. | ||
| Keywords | ||
| antidiabetic activity; gliclazide-alginate-gelatin beads; healthy and diabetic rats; pharmacokinetic-pharmacodynamic relationship; single and multiple dose; Wound healing | ||
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