盐酸倍他洛尔-蒙脱石离子交换微球混悬剂的制备及质量评价

Preparation and Quality Evaluation of Betaxolol Hydrochloride-montmorillonite Ion Exchange Microspheres Suspension

目的:将盐酸倍他洛尔-蒙脱石离子交换微球制备成眼用混悬剂,为新型微球混悬剂的眼部给药提供参考。方法:筛选盐酸倍他洛尔-蒙脱石离子交换微球混悬剂的辅料并进行制剂学评价,通过刺激性与离体角膜透过性试验考查混悬剂的生物学性质。结果:以0.15%卡波姆934P为助悬剂,0.01%聚山梨酯-80为润湿剂,制备的制剂稳定性良好,p H(7.0),渗透压(302 m Osm·kg-1),黏度(4.1 m Pa·s)和刺激性均符合眼用制剂要求。刺激性试验显示微球混悬剂对眼部组织无明显刺激性,贝特舒组结膜出现部分淋巴细胞浸润。角膜透过性试验中微球混悬剂表观渗透参数1.78×10-5cm·s-1,约为盐酸倍他洛尔溶液(3.57×10-5cm·s-1)的1/2倍和市售贝特舒(0.85×10-5cm·s-1)2倍。结论:离子交换微球可在一定程度上减缓药物的角膜透过性,虽然缓释性不及贝特舒,但刺激性显著低于贝特舒,具备一定的缓释性与低毒副作用。

Objective： To prepare betaxolol hydrochloride-montmorillonite ion exchange microspheres eye suspension. Method： Excipients of betaxolol hydrochloride-montmorillonite ion exchange microspheres eye suspension were screened and its preparation characters were evaluated, biological properties of microspheres suspension were investigated by eye irritation and isolated corneal permeability test. Result： Optimal combination was 0. 15% carbomer 934P as suspending agent and 0. 01% tween-80 as wetting agent. Its stability, pH value, osmotic pressure, viscosity and corneal irritation were complies with the requirement of ophthalmic preparations applications. During irritation test, there was no obviously irritating in the microspheres suspension group, but the Beiteshu group＇s conjunctiva appeared partly lymphocytic infiltrates. Isolated corneal permeability test showed that the suspension＇s apparent permeability coefficient （Papp） was 1.78 × 10^-5 cm .s-1, half of betaxolol hydrochloric solution （3.57 ×10^-5 cm.s-1） and twice of Beiteshu drops （0. 85 × 10^-5 cm .s-1 ）. Conclusion： It is shows that self-made ion exchange microspheres suspension possesses capability of sustained-release and extenuate drug toxicity.