Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
Department of Molecular Biology and Biochemistry, Molecular Microbiology Lab, Guru Nanak Dev University, Amritsar, 143005, India.
Daru. 2020 Jun;28(1):191-208. doi: 10.1007/s40199-020-00330-3. Epub 2020 Feb 7.
Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ.
Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols.
The optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in C and 2.73 and 1.98 fold in AUC , as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis.
The current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation. Graphical abstract Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.
坎格列净（CFZ）是一种新型 SGLT II 拮抗剂，口服给药后吸收不稳定。本研究旨在开发和评价喷雾干燥脂质体制剂（固体 SMEDDS），以提高 CFZ 的口服生物利用度和抗糖尿病活性。
通过喷雾干燥制备固体 SMEDDS，其中 Neusilin US2 用作吸附剂。对形成的固体 SMEDDS 进行物理化学和固态属性的表征。扫描电子显微镜（SEM）和透射电子显微镜（TEM）用于确认其球形形态。进行体外溶出度、离体渗透性和体内药代动力学研究，分别确定 CFZ 的释放速率、渗透速率和吸收曲线。根据标准方案进行药效学研究。
优化的固体 SMEDDS 表现出可接受的实际产率和流动性能，并具有增强的非晶化、纳米颗粒分布和可接受的药物含量。固体 SMEDDS 和重构 SMEDDS 的 SEM 和 TEM 分别证实了其球形形态。体外溶出度研究表明，CFZ 在各种溶出介质中具有多倍释放行为，而在大鼠空肠段观察到显著的渗透性。固体 SMEDDS 中 CFZ 的药代动力学研究表明，与纯 API 和市售制剂相比，C 和 AUC 分别提高了 2.53 倍和 1.43 倍，以及 2.73 倍和 1.98 倍。固体 SMEDDS 的药效学评价表明，CFZ 通过在大鼠中主要抑制 SGLT II，增强了其抗糖尿病活性，这从生化水平评估、尿糖排泄研究和 SGLT II 表达分析中可以明显看出。
本研究描述了 CFZ 在固体 SMEDD 制剂中的生物药剂学性质得到显著改善。
