Mooranian Armin, Negrulj Rebecca, Mathavan Sangeetha, Martinez Jorge, Sciarretta Jessica, Chen-Tan Nigel, Mukkur T K, Mikov Momir, Lalic-Popovic Mladena, Stojancevic Maja, Golocorbin-Kon Svetlana, Al-Salami Hani
Biotechnology and Drug Development Research Laboratory, School of Pharmacy , CHIRI Biosciences Research Precinct .
Pharm Dev Technol. 2015;20(6):702-9. doi: 10.3109/10837450.2014.915570. Epub 2014 May 5.
In previous studies, we have shown that a gliclazide-cholic acid derivative (G-CA) mixture resulted in an enhanced ileal permeation of G (ex vivo). When administered orally to diabetic rats, it brought about a significant hypoglycaemic effect. In this study, we aim to create a novel microencapsulated-formulation of G-CA with uniform and coherent structure that can be further tested in our rat model of type 1 diabetes (T1D). We also aim to examine the effect of CA addition to G microcapsules in the morphology, structure and excipients' compatibility of the newly designed microcapsules.
Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Complete characterizations of microcapsules were carried out.
The new G-CA-SA formulation is further optimized by the addition of CA exhibiting pseudoplastic-thixotropic rheological characteristics. Bead size remains similar after CA addition, the new microcapsules show no chemical interactions between the excipients and this was supported further by the spectral studies suggesting bead stability.
The new microencapsulated-formulation has good and uniform structural properties and may be suitable for oral delivery of antidiabetic-bile acid formulations.
在先前的研究中,我们已经表明,格列齐特-胆酸衍生物(G-CA)混合物可增强G在回肠的渗透作用(体外实验)。给糖尿病大鼠口服该混合物时,会产生显著的降血糖作用。在本研究中,我们旨在制备一种结构均匀且连贯的新型G-CA微囊制剂,以便在我们的1型糖尿病(T1D)大鼠模型中进一步测试。我们还旨在研究在G微囊中添加CA对新设计微囊的形态、结构和辅料相容性的影响。
使用我们实验室开发的基于Buchi的微囊化系统进行微囊化。分别以恒定比例(1:3:30)使用海藻酸钠(SA)聚合物制备两种制剂:G-SA(对照)和G-CA-SA(测试)。对微囊进行了全面表征。
通过添加具有假塑性-触变性流变学特性的CA,新的G-CA-SA制剂得到进一步优化。添加CA后珠粒大小保持相似,新微囊的辅料之间未显示出化学相互作用,光谱研究进一步支持了珠粒的稳定性。
新的微囊制剂具有良好且均匀的结构特性,可能适用于口服抗糖尿病-胆汁酸制剂。