Solidified Self-Nanoemulsifying Formulation for Oral Delivery of Combinatorial Therapeutic Regimen: Part I. Formulation Development, Statistical Optimization, and In Vitro Characterization
Solidified Self-Nanoemulsifying Formulation for Oral Delivery of Combinatorial Therapeutic Regimen: Part I. Formulation Development, Statistical Optimization, and In Vitro Characterization
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DOI：
10.1007/s11095-013-1213-2
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发表时间：
2014-04-01
影响因子：
3.7
通讯作者：
Jain, Sanyog
中科院分区：
文献类型：
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作者：
Jain, Amit K.;Thanki, Kaushik;Jain, Sanyog
本工作报告了合理的开发和表征的固体自纳米乳化药物递送系统的口服组合（他莫昔芬和槲皮素）的治疗方案，选择合适的油制备液体SNEDDS基于最大饱和溶解度的药物，表面活性剂和助表面活性剂，根据其乳化能力。采用极顶点混料设计和3（2）完全析因设计对SNEDDS液体制剂和冻干混合液中固体载体浓度进行优化。最后，对所开发的制剂进行了广泛的表征，并在Caco-2细胞培养模型中评价了体外细胞摄取。极端顶点混合设计表明，0.663的期望值，对应于40：30：30 w/w作为液体SNEDDS中油（CapmulA（R）MCM）、表面活性剂（Cremophor RH 40）和助表面活性剂（Labrafil 1944 CS）的最佳比例，其增溶了高量的他莫昔芬（10 mg/g）和槲皮素（19.44 mg/g）。A，3（2）全因子设计显示，当分别根据总固体含量和液体SNEDDS：Aerosil 200比率测量时，所选固体载体（Aerosil 200）的最佳浓度为5.24%w/w和1.61。开发的制剂显示瞬时乳化（< 2分钟），同时即使在加速稳定性条件下储存6个月后也保持所有质量属性。最后，开发的配方显示，9.63倍和8.44倍高的Caco-2摄取他莫昔芬和槲皮素，分别与游离药物counters.The开发的配方策略揭示了一个巨大的潜力，口服联合药物具有最大的临床意义。
The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen.Suitable oil for the preparation of liquid SNEDDS was selected based on the maximum saturation solubility of both the drugs while surfactant and co-surfactant were selected based on their emulsification ability. Extreme vertices mixture design and 3(2) full factorial design were implemented for optimization of liquid SNEDDS and concentration of solid carrier in lyophilization mixture. Finally, extensive characterization of the developed formulation was performed and in vitro cellular uptake was evaluated in Caco-2 cell culture model.Extreme vertices mixture design indicated the desirability of 0.663, corresponded to 40:30:30 w/w as optimum ratio of oil (CapmulA (R) MCM), surfactant (Cremophor RH 40) and co-surfactant (Labrafil 1944CS) in liquid SNEDDS, which solubilized high amount of tamoxifen (10 mg/g) and quercetin (19.44 mg/g). A, 3(2) full factorial design revealed the optimum concentration of the selected solid carrier (Aerosil 200) of 5.24% w/w and 1.61, when measured in terms of total solid content and liquid SNEDDS: Aerosil 200 ratio, respectively. The developed formulation revealed instantaneous emulsification (in < 2 min), while maintaning all the quality attributes even after storage at accelerated stability condition for 6 months. Finally, the developed formulation revealed 9.63-fold and 8.44-fold higher Caco-2 uptake of tamoxifen and quercetin, respectively in comparison with free drug counterparts.The developed formulation strategy revealed a great potential for oral delivery of combination drugs having utmost clinical relevance.