Adibkia Khosro, Ghajar Solmaz, Osouli-Bostanabad Karim, Balaei Niloufar, Emami Shahram, Barzegar-Jalali Mohammad
Research Center for Pharmaceutical Nanotechnology and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2019 Jun;9(2):231-240. doi: 10.15171/apb.2019.026. Epub 2019 Jun 1.
In the current study, electrospraying was directed as a novel alternative approach to improve the physicochemical attributes of gliclazide (GLC), as a poorly water-soluble drug, by creating nanocrystalline/amorphous solid dispersions (ESSs). ESSs were formulated using Eudragit® RS100 and polyethylene glycol (PEG) 6000 as polymeric carriers at various drug: polymer ratios (i.e. 1:5 and 1:10) with different total solution concentrations of 10, 15, and 20% w/v. Morphological, physicochemical, and in-vitro release characteristics of the developed formulations were assessed. Furthermore, GLC dissolution behaviors from ESSs were fitted to various models in order to realize the drug release mechanism. Field emission scanning electron microscopy analyses revealed that the size and morphology of the ESSs were affected by the drug: polymer ratios and solution concentrations. The polymer ratio augmentation led to increase in the particle size while the solution concentration enhancement yielded in a fiber establishment. Differential scanning calorimetry and powder X-ray diffraction investigations demonstrated that the ESSs were present in an amorphous state. Furthermore, the in vitro drug release studies depicted that the samples prepared employing PEG 6000 as carrier enhanced the dissolution rate and the model that appropriately fitted the release behavior of ESSs was Weibull model, where demonstrating a Fickian diffusion as the leading release mechanism. Fourier-transform infrared spectroscopy results showed a probability of complexation or hydrogen bonding, development between GLC and the polymers in the solid state. Hence the electrospraying system avails the both nanosizing and amorphization advantages, therefore, it can be efficiently applied to formulating of ESSs of BCS Class II drugs.
在当前研究中，电喷雾被用作一种新型替代方法，通过制备纳米晶/无定形固体分散体（ESSs）来改善格列齐特（GLC）这种难溶性药物的物理化学性质。使用Eudragit® RS100和聚乙二醇（PEG）6000作为聚合物载体，以不同的药物:聚合物比例（即1:5和1:10）以及10%、15%和20% w/v的不同总溶液浓度来制备ESSs。对所开发制剂的形态、物理化学和体外释放特性进行了评估。此外，将ESSs中GLC的溶解行为拟合到各种模型中，以了解药物释放机制。场发射扫描电子显微镜分析表明，ESSs的尺寸和形态受药物:聚合物比例和溶液浓度的影响。聚合物比例增加导致粒径增大，而溶液浓度增加则产生纤维结构。差示扫描量热法和粉末X射线衍射研究表明，ESSs呈无定形状态。此外，体外药物释放研究表明，以PEG 6000作为载体制备的样品提高了溶解速率，适用于拟合ESSs释放行为的模型是威布尔模型，表明以菲克扩散作为主要释放机制。傅里叶变换红外光谱结果表明，GLC与固态聚合物之间存在络合或氢键形成的可能性。因此，电喷雾系统兼具纳米化和无定形化的优势，所以它可以有效地应用于BCS II类药物ESSs的制备。
