School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Pharm. 2020 Mar 30;578:119184. doi: 10.1016/j.ijpharm.2020.119184. Epub 2020 Feb 26.
Conventional ophthalmic eye drops are limited by their rapid elimination rate and short time of action. Ion exchange resin has been used to achieve sustained ocular drug delivery but the high selectivity of drug molecules restricts its broad application. In situ gel system seems to be a good strategy to address these problems but the influence of in situ gel type on the sustained release behavior and tissue distribution after ocular application is unclear. Therefore, in this study, using betaxolol hydrochloride as a model drug, poloxamer 407 and methylcellulose as the carriers, two thermosensitive in situ gel systems were prepared and characterized. Influence of formulation composition type and concentration on in vitro drug release was studied. Tissue distribution after ocular delivery of two different thermosensitive in situ gels was studied and compared with commercial BH eye drop (Betoptic S®). In vitro studies demonstrated that addition of 4% HPMC 606W in 15% P407 solution and 5% PEG4000 in 2% MC solution obtained gels with appropriate gelation temperature and similar sustained drug release rate. In vivo tissue distribution study indicated that they presented similar drug concentration in cornea, iris-ciliary and aqueous humor irrespective of gel type, with higher drug concentration achieved after 4 h compared to the commercial resin suspension eye drops. The AUC and MRT of the two in situ gel eye drops were 2 times higher than that of the commercial resin suspension eye drops in cornea. In conclusion, the two thermosensitive in situ gels have prolonged drug release after ocular drug delivery compared with ion exchange resin eye drops, implying their potential applications in clinic with broad drug adoptability.
传统的眼科眼药水受到其快速消除率和作用时间短的限制。离子交换树脂已被用于实现持续的眼部药物递送，但药物分子的高选择性限制了其广泛的应用。原位凝胶系统似乎是解决这些问题的好策略，但原位凝胶类型对眼部应用后的持续释放行为和组织分布的影响尚不清楚。因此，在这项研究中，以盐酸倍他洛尔为模型药物，以泊洛沙姆 407 和甲基纤维素为载体，制备并表征了两种温敏型原位凝胶。研究了配方组成类型和浓度对体外药物释放的影响。研究并比较了两种不同温敏原位凝胶眼部给药后的组织分布与商业 BH 眼药水（Betoptic S®）。体外研究表明，在 15% P407 溶液中添加 4% HPMC 606W 和在 2% MC 溶液中添加 5% PEG4000 可获得适当的胶凝温度和相似的持续药物释放速率的凝胶。体内组织分布研究表明，无论凝胶类型如何，它们在角膜、虹膜睫状体和房水中均表现出相似的药物浓度，与商业树脂混悬液眼药水相比，4 小时后药物浓度更高。两种温敏原位凝胶滴眼剂在角膜中的 AUC 和 MRT 是商业树脂混悬液滴眼剂的 2 倍。总之，与离子交换树脂滴眼剂相比，这两种温敏原位凝胶在眼部给药后具有延长的药物释放，这意味着它们具有在临床上广泛应用的潜力。
