吲哚美辛二元醇质体凝胶剂的制备与质量研究

Preparation and in Vitro Evaluation of Indomethacin Binary Ethosomes Gel

目的:优化吲哚美辛(IND)二元醇质体凝胶的处方工艺,并进行药效学研究和稳定性考查。方法:以平均粒径Y1和包封率Y2为因变量,磷脂用量X1、混合醇用量X_(2)、丙二醇用量X_(3)为自变量,采用星点设计-效应面法优化IND二元醇质体的制备工艺,并与卡波姆凝胶基质以1∶1比例研和制备IND二元醇质体凝胶,通过改良的Franz扩散池法考查IND凝胶、纳米乳与二元醇质体凝胶的体外透皮性能并进行IND二元醇质体的初步稳定性考查;采用热板法和醋酸扭体法考查IND三种制剂的体内镇痛作用。结果:最优处方工艺为IND0.50g,磷脂0.46g,混合醇8.45mL,丙二醇2.15mL,制备的IND二元醇质体凝胶的平均粒径为(81.80±1.04)nm,包封率为(72.61±1.01)%,与预测值相对误差分别为2.36%、2.29%。IND二元醇质体凝胶的稳态渗透速率常数为(0.646 7±0.007 30)μg·cm^(-2)·h^(-1),是普通凝胶的2.16倍,纳米乳的1.43倍;IND二元醇质体凝胶能明显抑制小鼠的热板添足反应和醋酸扭体反应。结论:制备的IND二元醇质体凝胶剂粒径小,分布较为均匀,具有良好的体外透皮吸收性能和体内镇痛作用,稳定性良好,为IND用于局部炎症治疗的新剂型研究提供依据。

Objective:To optimize the formulation process of indomethacin(IND)binary ethosomes gel,and research its pharmacodynamics and stability.Methods:With the mean particle size Y1 and encapsulation rate Y2 as dependent vari‐ables,the amount of phospholipid X1,the amount of mixed alcohol X2,and the amount of propylene glycol X3 as indepen‐dent variables,the preparation process of IND diethosome was optimized by central point design and response surface method.IND binary ethosomes gel was prepared in 1∶1 ratio with Carbomer gel matrix.The in vitro transdermal properties of IND gel,nano emulsion and binary ethosomes gel were investigated by modified Franz diffusion cell method,and the pre‐liminary stability of IND binary ethosomes gel was investigated,and in vivo analgesic effects of IND were investigated by hot plate method and acetic acid writhing method.Results:The optimal formulation process was IND 0.50 g,phospholipid 0.46 g,mixed alcohol 8.45 mL,propylene glycol 2.15 mL,the average particle size of IND binary ethosomes gel was(81.80±1.04)nm,encapsulation rate was(72.61±1.01)%.The relative errors were 2.36%and 2.29%,respectively.The steady permeation rate constant of IND binary ethosomes gel is(0.6467±0.0073)μg·cm^(-2)·h^(-1),which is 2.16 times of that of ordinary gel and 1.43 times of that of nano emulsion,IND binary ethosomes gel could significantly inhibit hot plate load‐ing and acetic acid writhing in mice.Conclusion:The prepared IND binary ethosomes gel has small particle size,relatively uniform distribution,good transdermal absorption performance,in vivo analgesia and good stability,which provides a ba‐sis for the study of a new dosage form of IND for the treatment of local inflammation.