美洛昔康磷脂复合物过饱和自纳米乳的制备及体外质量评价

Preparation and in vitro quality evaluation of meloxicam phospholipid complex supersaturated self-nanoemulsion

目的制备美洛昔康磷脂复合物过饱和自纳米乳(MLX-PC-S-SNEDDS),并对其进行体外质量评价。方法首先将美洛昔康(MLX)与磷脂制备成美洛昔康磷脂复合物(MLX-PC),然后将其制成自纳米乳化给药系统,同时加入沉淀抑制剂使体系达到一定过饱和度。以粒径、粒径分散系数(PDI)与载药量为评价指标,采用星点设计联合归一化法综合优选最佳处方。并以体外溶出度和稳定性为指标进行体外评价。结果制备的美洛昔康自纳米乳(MLX-SNEDDS)、美洛昔康过饱和自纳米乳(MLX-S-SNEDDS)、MLX-PC-S-SNEDDS均为黄色透明均一的油状液,乳滴呈类球形且分布均匀,粒径均小于30 nm,Zeta电位分别为(-1.44±0.11)、(-5.56±0.61)、(-7.07±0.88)mV,制剂的稳定性良好,乳化后粒径无明显变化。MLX-S-SNEDDS和MLX-PC-S-SNEDDS载药量分别为4.82 mg·mL^(-1)和8.73 mg·mL^(-1)。MLX-PC-S-SNEDDS在提高MLX载药量同时显著提高体外溶出速率及溶出程度。结论成功制备了粒径均一、载药量较高和稳定性好的MLX-PC-S-SNEDDS,可提高患者服药顺应性,为改善难溶性药物水溶性提供了有益参考,在提高药物的生物利用度方面更具潜力。

Objective To prepare the meloxicam(MLX)phospholipid complex(MLX-PC)supersaturated self-nanoemulsion and evaluate its quality in vitro.Methods MLX and phospholipid were prepared into MLX-PC,which was further made into the nano-emulsifying drug delivery system.At the same time,precipitation inhibitor was added to reach a certain degree of supersaturation.Based on the particle size,particle size dispersion coefficient(PDI)and drug loading,the optimal formulation was evaluated by the central composite design normalization method.The dissolution rate and stability in vitro were used as the indexes for in vitro evaluation.Results The prepared meloxicam selfnanoemulsion(MLX-SNEDDS),and meloxicam supersaturated self-nanoemulsion(MLX-S-SNEDDS),meloxicam phospholipid complex supersaturated self-nanoemulsion(MLX-PC-S-SNEDDS)were all yellow,transparent and uniform oily liquids,with spherical emulsion droplets and uniform distribution.The particle diameters were all less than 30 nm,and the Zeta potentials were(-1.44±0.11)mV,(-5.56±0.61)mV,and(-7.07±0.88)mV,respectively.The stability of the formulations was well,and the particle size hardly changed after the emulsification.The drug loadings of MLX-S-SNEDDS and MLX-PC-S-SNEDDS were 4.82 mg·mL^(-1)and 8.73 mg·mL^(-1).MLX-PC-S-SNEDDS could significantly increase the dissolution rate and degree in vitro while increasing the MLX drug loading.Conclusion MLX-PC-S-SNEDDS with uniform particle size,high drug loading and good stability is prepared,which can improve patients’drug compliance,provide reference for improving the water solubility of insoluble drugs and the bioavailability of drugs.