马来酸噻吗洛尔眼用温敏凝胶的处方筛选与体外释放评价

Formulation and preparation optimization of ocular thermo-sensitive gel of timolol maleate

目的:筛选马来酸噻吗洛尔眼用温敏型凝胶优化处方,并对其体外释放进行评价。方法:选用泊洛沙姆P407、P188为载体材料制备眼用温敏凝胶,测定不同处方的凝胶前体溶液分别在未经处理和经人工泪液稀释条件下,从溶液态转变为凝胶态的胶凝温度,通过星点设计-效应面法筛选优化处方,并考察胶凝时间和释放行为。结果:根据温敏凝胶保存和使用的温度要求,筛选出优化处方为P407∶P188(24.25%∶1.56%)。前体溶液能够在34℃人工泪液中迅速形成凝胶,并在体外缓慢释放6 h以上。结论:经过筛选并制备出的噻吗洛尔温敏型凝胶具有良好的载药能力、稳定性及释放性能,满足眼用制剂质量要求和实际应用要求。

OBJECTIVE To optimize formulation of ophthalmic thermo-sensitive gel of timolol maleate,and evaluate its in vitro drug release efficiency.METHODS Poloxamer 407 and Poloxamer 188 were used as the thermo-sensitive materials and central composite design was adopted to optimize formulation of gel by measuring gelation temperature with and without artificial tears.Meanwhile,gelation time,adhesion force and release behavior were investigated.RESULTS According to practical need that thermo-sensitive gel precursor solution should keep liquid state at normal atmospheric temperatures and gelate at ocular surface temperature of 32 ℃,the optimized formula was selected as P407∶P188（24.25%∶1.56%）.Optimized drug loaded precursor solution had been successfully prepared with low viscosity,proper pH and osmotic pressure,and could transit into gel rapidly in 34 ℃ artificial tears.Drug release profile showed timolol maleate gel formed from optimal formulation could attain 6h sustained release behavior.CONCLUSION The prepared thermo-sensitive gel of timolol maleate shows good gelling capacity,stability,drug release behavior and high drug loading,which indicates that the dosage form can be adopted for ophthalmic therapy.