他克莫司眼用微乳的制备及载药量测定方法

Preparation of tacrolimus ophthalmic microemulsion and investigation of the method for determination of loaded drugs

目的制备他克莫司眼用微乳剂,并建立其载药量的测定方法。方法采用溶解度实验与滴定法绘制的伪三元相图研究各处方成分对微乳形成的影响,结合星点设计-效应面法优化微乳处方;通过高效液相色谱法(HPLC)建立他克莫司微乳载药量检测方法并进行方法学验证。结果理想的他克莫司眼用微乳剂是以Labrafil M1944CS为油相,Kolliphor EL为乳化剂,Labrasol为助乳化剂,双蒸水为水相形成的o/w型微乳;其pH值为7.57±0.02,渗透压为(305±1.68)mOsm/kg,平均粒径为(22.01±1.80)nm。HPLC法测定微乳中他克莫司的平均载药量为(0.9924±0.0084)mg/ml(n=3)。结论所制备的眼用微乳为粒径小且分布均匀的热力学稳定体系;建立的HPLC法测定他克莫司眼用微乳的载药量简单准确,为该制剂的进一步研究奠定了基础。

Objective To prepare tacrolimus ophthalmic microemulsion and establish a method for the determination of load- ed drugs. Methods The solubility was evaluated and then the pseudo-ternary phase diagram was drawn by titration to investigate the effect of each formulation component on microemulsion formation. The central composite design-response surface methodology was used for optimizing microemulsion formulation. The method for the determination of loaded drugs in the tacrolimus ophthalmic micro- emulsion was established using high performance liquid chromatography （HPLC）. Results The ideal o/w ophthalmic microemulsion of taerolimus could be prepared with Labrafil M1944CS as oil phase, Kolliphor EL as emulsifier, Labrasol as co-emulsifier and double distilled water as aqueous phase. Its pH value was 7.57±0.02, osmotic pressure was （305±1.68） mOsm/kg, and mean particle diame- ter was （22.01± 1.80） nm. The tacrolimus ophthalmic microemulsions was loaded （0.9924±0.0084） mg/ml of the drugs as determined by HPLC method. Conclusion The prepared ophthalmic microemulsion is a thermodynamically stable system with small particle size and uniform distribution. The established HPLC method is simple and accurate for the determination of tacrolimus in the ophthalmic microemulsion, which provides a useful method for further study.