Aggarwal Deepika, Kaur Indu P
University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India.
Int J Pharm. 2005 Feb 16;290(1-2):155-9. doi: 10.1016/j.ijpharm.2004.10.026. Epub 2005 Jan 5.
In the present study chitosan (REVTMbio1) or Carbopol (REVTMbio2 and 3) coated niosomal timolol maleate (0.25%) formulations were prepared by reverse phase evaporation (REV) and compared to timolol solution (TMS; 0.25%) in terms of in vitro release and IOP lowering pharmacodynamic effect. The in vitro release phase of timolol (91% release in 2 h) was extended significantly by its incorporation into niosomes and further by the polymer coating (40-43% release upto 10 h). The developed formulations were evaluated for their pharmacodynamics in albino rabbits, by measuring intraocular pressure (IOP) using a non-contact pneumatonometer, and were compared to a marketed in situ gel forming solution of timolol (Timolet GFS, 0.5%; Sun Pharma). REVTMbio1 formulation showed a more sustained effect of upto 8h (vis a vis 6 h for carbopol-coated niosomes). TMS in comparison showed effect for only 2 h though the peak effect was slightly more (14%). Lowering of IOP in the contralateral eye (20-40% as compared to 100% in case of TMS), considerably reduces with REV and REVbio formulations indicating lesser systemic side effects. Moreover, the results of REVTMbio1formulation containing 0.25% of timolol maleate compared well with the 0.5% marketed gel formulation, indicating our formulation to be significantly better considering that similar effect is obtained at half the concentration. The later becomes especially important in context to the cardiovascular side effects associated with ocular timolol maleate therapy.
在本研究中，采用逆相蒸发法（REV）制备了壳聚糖（REVTMbio1）或卡波姆（REVTMbio2和3）包衣的马来酸噻吗洛尔（0.25%）脂质体制剂，并在体外释放和降低眼压的药效学作用方面与噻吗洛尔溶液（TMS；0.25%）进行了比较。通过将噻吗洛尔包封于脂质体中，其体外释放阶段（2小时内释放91%）得到显著延长，而聚合物包衣进一步延长了释放时间（10小时内释放40 - 43%）。通过使用非接触式眼压计测量白化兔的眼压，对所制备的制剂进行了药效学评估，并与市售的噻吗洛尔原位凝胶形成溶液（Timolet GFS，0.5%；太阳制药公司）进行了比较。REVTMbio1制剂显示出长达8小时的更持久效果（相比之下，卡波姆包衣的脂质体为6小时）。相比之下，TMS仅在2小时内显示出效果，尽管峰值效果略高（14%）。与TMS使对侧眼眼压降低100%相比，REV和REVbio制剂使对侧眼眼压降低20 - 40%，这表明全身副作用较小。此外，含有0.25%马来酸噻吗洛尔的REVTMbio1制剂的结果与0.5%的市售凝胶制剂相当，这表明在浓度减半的情况下获得了相似的效果，因此我们的制剂明显更好。考虑到与眼部马来酸噻吗洛尔治疗相关的心血管副作用，这一点尤为重要。
