Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan.
Department of Pharmacy, University of Malakand, Chakdara, Khyber Pakhtunkhwa, 18800, Pakistan.
Int J Nanomedicine. 2019 Aug 6;14:6287-6296. doi: 10.2147/IJN.S210548. eCollection 2019.
We aimed to enhance the solubility, dissolution rate, oral bioavailability, and α-glucosidase inhibition of glimepiride (Glm) by fabricating its nanosuspension using a precipitation-ultrasonication approach.
Glm nanosuspensions were fabricated using optimized processing conditions. Characterization of Glm was performed using Malvern Zetasizer, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Minimum particle size and polydispersity index (PDI) values were found to be 152.4±2.42 nm and 0.23±0.01, respectively, using hydroxypropyl methylcellulose: 6 cPs, 1% w/v, polyvinylpyrrolidone K30 1% w/v, and sodium lauryl sulfate 0.12% w/v, keeping ultrasonication power input at 400 W, with 15 minutes' processing at 3-second pauses. In vivo oral bioavailability was assessed using rabbits as a model.
The saturation solubility of the Glm nanosuspensions was substantially enhanced 3.14-fold and 5.77-fold compared to unprocessed drug in stabilizer solution and unprocessed active pharmaceutical ingredient. Also, the dissolution rate of the nanosuspensions ws substantially boosted when compared to the marketed formulation and unprocessed drug candidate. The results showed that >85% of Glm nanosuspensions dissolved in the first 10 minutes compared to 10.17% of unprocessed Glm), 42.19% of microsuspensions, and 19.94% of marketed tablets. In-vivo studies conducted in animals, i.e. rabbits, demonstrated that maximum concentration and AUC with oral dosing were twofold (5 mg/kg) and 1.74-fold (2.5 mg/kg) and 1.80-fold (5 mg/kg) and 1.63-fold (2.5 mg/kg), respectively, and compared with the unprocessed drug formulation. In-vitro α-glucosidase inhibition results showed that fabricated nanosuspensions had a pronounced effect compared to unprocessed drug.
The optimized batch fabricated by ultrasonication-assisted precipitation can be useful in boosting oral bioavailability, which may be accredited to enhanced solubility and dissolution rate of Glm, ultimately resulting in its faster rate of absorption due to nanonization.
通过沉淀-超声法制备格列美脲（Glm）纳米混悬剂，提高其溶解度、溶出速率、口服生物利用度和α-葡萄糖苷酶抑制作用。
采用优化的工艺条件制备 Glm 纳米混悬剂。采用 Malvern Zetasizer、扫描电子显微镜、透射电子显微镜、差示扫描量热法和粉末 X 射线衍射对 Glm 进行表征。结果表明，羟丙基甲基纤维素：6 cPs、1%w/v、聚乙烯吡咯烷酮 K30 1%w/v 和十二烷基硫酸钠 0.12%w/v，超声功率输入 400 W，处理 15 分钟，每 3 秒暂停 1 次，可获得最小粒径和多分散指数（PDI）值分别为 152.4±2.42nm 和 0.23±0.01。采用兔作为模型评估体内口服生物利用度。
与稳定剂溶液中的未加工药物和未加工原料药相比，Glm 纳米混悬剂的饱和溶解度分别显著提高了 3.14 倍和 5.77 倍。与市售制剂和未加工药物相比，纳米混悬剂的溶出速率也显著提高。结果表明，与未加工的 Glm（10.17%）相比，>85%的 Glm 纳米混悬剂在最初 10 分钟内溶解，与未加工的 Glm 相比，42.19%的微混悬剂和 19.94%的市售片剂溶解。在动物（即兔子）体内进行的研究表明，口服给药时，最大浓度和 AUC 分别为 2 倍（5mg/kg）和 1.74 倍（2.5mg/kg）和 1.80 倍（5mg/kg）和 1.63 倍（2.5mg/kg），与未加工的药物制剂相比。体外α-葡萄糖苷酶抑制结果表明，与未加工药物相比，制备的纳米混悬剂具有显著的效果。
超声辅助沉淀法制备的优化批次可提高口服生物利用度，这可能归因于 Glm 的溶解度和溶出速率提高，最终由于纳米化导致其吸收速度加快。
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