El-Ashmawy Ahmed A, Abdou Aya R, Taha Nesrin F, Elsayed Ebtesam W, Mahmoud Khaled M, Emara Laila H
Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir st.), Dokki, Giza, Egypt.
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, P.O.12622, 33 EL Bohouth St. (former EL Tahrir st.), Dokki, Giza, Egypt.
AAPS PharmSciTech. 2021 Apr 30;22(4):146. doi: 10.1208/s12249-021-02008-8.
In vitro and in vivo studies of gliclazide (GLZ)-loaded freeze-dried alginate-gelatin (AL-GL) beads were carried out, aiming to modify its oral bioavailability. Crosslinked freeze-dried GLZ AL-GL beads (particle size: 1.5- and 3.0-mm) were prepared. In vitro evaluation of GLZ AL-GL beads included SEM, DSC, FT-IR, and release rate study in gradient media. In vivo study was single-dose (4 mg/kg), randomized, parallel-group design, two-treatment (T: test GLZ AL-GL beads and R: reference product Diamicron® 30-mg MR tablet) conducted in 96 healthy rats. Each group was subdivided into 2 sub-groups (G1 and G2) having different blood sampling schemes for up to 72 h. Assessment of level A in-vitro-in-vivo correlation (IVIVC) model was carried out. AL-GL beads successfully increased GLZ release rate compared to R. GLZ percent released (Q) was 109.34, 86.85, and 43.43% for 1.5-mm and 3.0-mm beads and R, respectively. DSC analysis confirmed the interaction of AL-GL via crosslinking. No chemical interaction of GLZ has occurred as proved by FT-IR. Relative bioavailability (T/R) for AUC was 132.45% for G1 and 146.16% for G2. No significant differences between T and R in the primary pharmacokinetic parameters were determined. T values were found to be earlier in the case of G1 than those of G2. A secondary absorption peak of GLZ was clearly detected in the case of R while its sharpness was minimized in T. High IVIVC was established, and hence, the proposed in vitro release model perfectly correlated with the in vivo study. The current study design might be a platform to enable panoramic view for GLZ variability in vivo.
开展了载有格列齐特（GLZ）的冻干海藻酸钠 - 明胶（AL - GL）微球的体外和体内研究，旨在改善其口服生物利用度。制备了交联冻干GLZ AL - GL微球（粒径：1.5毫米和3.0毫米）。GLZ AL - GL微球的体外评估包括扫描电子显微镜（SEM）、差示扫描量热法（DSC）、傅里叶变换红外光谱法（FT - IR）以及在梯度介质中的释放速率研究。体内研究采用单剂量（4毫克/千克）、随机、平行组设计，在96只健康大鼠中进行两种治疗（T：试验性GLZ AL - GL微球和R：参比产品达美康®30毫克缓释片）。每组再细分为2个亚组（G1和G2），具有不同的采血方案，最长至72小时。进行了A级体外 - 体内相关性（IVIVC）模型评估。与参比产品相比，AL - GL微球成功提高了GLZ的释放速率。1.5毫米和3.0毫米微球以及参比产品的GLZ释放百分比（Q）分别为109.34%、86.85%和43.43%。DSC分析证实了AL - GL通过交联的相互作用。FT - IR证明GLZ未发生化学相互作用。G1组AUC的相对生物利用度（T/R）为132.45%，G2组为146.16%。未确定T和R在主要药代动力学参数方面的显著差异。发现G1组的达峰时间比G2组更早。参比产品中明显检测到GLZ的二次吸收峰，而在试验组中其尖锐度最小化。建立了高度的IVIVC，因此，所提出的体外释放模型与体内研究完美相关。当前的研究设计可能是一个平台，能够全面了解GLZ在体内的变异性。
