Kevadiya Bhavesh D, Chen Liang, Zhang Lu, Thomas Midhun B, Davé Rajesh N
New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Warren Street, Newark, NJ 07102, USA.
Pandorum Technologies Pvt Ltd, Bangalore Bioinnovation Centre, Helix Biotech Park, Electronic City Phase 1, Bangalore, Karnataka 560100, India.
Pharmaceuticals (Basel). 2019 Jul 16;12(3):109. doi: 10.3390/ph12030109.
Hydrophobic drug nanocrystals (NCs) manufactured by particle engineering have been extensively investigated for enhanced oral bioavailability and therapeutic effectiveness. However, there are significant drawbacks, including fast dissolution of the nanocrystals in the gastric environment, leading to physicochemical instability. To solves this issue, we developed an innovative technique that involves the encapsulation of nanocrystals in composite spherical microparticles (NCSMs). Fenofibrate (FNB) NCs (FNB-NCs) manufactured by a wet stirred media milling (WSMM) technique and an ionotropic crosslinking method were used for FNB-NC encapsulation within gastroresistant NCSMs. Various solid-state methods were used for characterizing NCSMs. The pH-sensitive NCSMs showed a site-specific release pattern at alkaline pH and nearly 0% release at low pH (gastric environment). This phenomenon was confirmed by a real-time in situ UV-imaging system known as the surface dissolution imager (SDI), which was used to monitor drug release events by measuring the color intensity and concentration gradient formation. All these results proved that our NCSM approach is an innovative idea in oral drug delivery systems, as it resolves significant challenges in the intestine-specific release of hydrophobic drugs while avoiding fast dissolution or burst release.
通过颗粒工程制造的疏水性药物纳米晶体（NCs）已被广泛研究，以提高口服生物利用度和治疗效果。然而，存在一些重大缺点，包括纳米晶体在胃环境中快速溶解，导致物理化学不稳定性。为了解决这个问题，我们开发了一种创新技术，即将纳米晶体封装在复合球形微粒（NCSMs）中。通过湿搅拌介质研磨（WSMM）技术和离子交联方法制备的非诺贝特（FNB）纳米晶体（FNB-NCs）被用于将FNB-NC封装在耐胃酸的NCSMs中。采用各种固态方法对NCSMs进行表征。pH敏感的NCSMs在碱性pH下呈现出特定部位的释放模式，在低pH（胃环境）下释放率接近0%。这种现象通过一种称为表面溶解成像仪（SDI）的实时原位紫外成像系统得到证实，该系统用于通过测量颜色强度和浓度梯度形成来监测药物释放事件。所有这些结果证明，我们的NCSM方法是口服药物递送系统中的一个创新理念，因为它解决了疏水性药物在肠道特异性释放中的重大挑战，同时避免了快速溶解或突释。
