Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, No. 1, QianJiang Road, Hefei, AnHui, People's Republic of China.
Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, China.
AAPS PharmSciTech. 2020 Sep 4;21(7):253. doi: 10.1208/s12249-020-01791-0.
We developed a pH-triggered in situ gel (ISG) for ocular delivery of vinpocetine to achieve systemic absorption and a brain-targeting effect in rats. Carbopol acted as a gelling agent combined with hydroxypropyl methylcellulose (HPMC) as a viscosity-enhancing agent. The concentration of Carbopol (0.2%, w/v) and HPMC (1.5%, w/v) was optimized for the ISG system. The optimized formulation was evaluated for studies on release in vitro, rheology, differential scanning calorimetry, ocular irritation, residence time, and in vivo pharmacokinetics. The vinpocetine ISG stayed longer in rabbit eyes than vinpocetine ointment. In vivo pharmacokinetics showed that compared with vinpocetine ointment, vinpocetine ISG attained a peak plasma concentration and area under the curve that was 1-2 folds greater in rat plasma. The Drug Targeting Index (DTI) was 1.06 and 1.26 for vinpocetine ointment and vinpocetine ISG, respectively, after ocular administration, showing that vinpocetine ISG had better distribution in rat brain. These results revealed that a pH-triggered ISG system via ocular administration could be an alternative approach compared with traditional ophthalmic formulations.
我们开发了一种 pH 触发的眼用原位凝胶（ISG），用于将长春西汀递送至大鼠体内，以实现全身吸收和脑靶向作用。卡波姆作为胶凝剂，与羟丙基甲基纤维素（HPMC）联合使用作为增稠剂。卡波姆（0.2%，w/v）和 HPMC（1.5%，w/v）的浓度被优化用于 ISG 系统。对优化的配方进行了体外释放、流变学、差示扫描量热法、眼刺激性、驻留时间和体内药代动力学研究。与长春西汀软膏相比，长春西汀 ISG 在兔眼中停留时间更长。体内药代动力学研究表明，与长春西汀软膏相比，长春西汀 ISG 在大鼠血浆中的达峰浓度和曲线下面积分别增加了 1-2 倍。眼用后，长春西汀软膏和长春西汀 ISG 的药物靶向指数（DTI）分别为 1.06 和 1.26，表明长春西汀 ISG 在大鼠脑内的分布更好。这些结果表明，与传统的眼用制剂相比，经眼部给药的 pH 触发 ISG 系统可能是一种替代方法。
