Purpose

In this work, praziquantel (PZQ) was incorporated into self-emulsifying drug delivery system (SEDDS) formulations to demonstrate that the increased apparent solubility and dissolution rate enhance intestinal permeation.

Methods

Solubility measurements of PZQ were performed in lipid excipients and hydrophilic substances; ternary phase diagrams were constructed with the excipients in which PZQ showed increased solubility. SEDDS formulations were characterized by globule size, the polydispersity index, zeta potential, the self-emulsification time, and morphology by scanning and transmission electron microscopy. The formulations were evaluated by performing in vitro dissolution profiles and permeation profiles in an ex vivo model.

Results

Four SEDDS formulations were identified that increased the apparent solubility of praziquantel by 60–150 times. The dispersion sizes obtained were < 350 nm, with polydispersity index values < 0.3, dispersion times < 60 s, and zeta potential values < −25 mV. A notable increase in the PZQ dissolution rate was obtained compared with the reference drug product. The permeation profiles were adjusted to a first-order kinetic model, obtaining an apparent absorption rate constant (K_ab) up to 18 times higher for SEDDS formulations than for PZQ powder, while the apparent permeability (P_app) and the effective intestinal permeability (P_eff) values increased up to 18 times for SEDDS formulations compared with PZQ powder.

Conclusion

The incorporation of PZQ into a SEDDS increases its apparent solubility and dissolution rate, changes that significantly enhance the processes of intestinal permeability. This behavior can be applied to support formulations of drugs belonging to class IV of the biopharmaceutical classification system.

中文翻译：

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吡喹酮增强体外渗透自乳化给药系统

目的

在这项工作中，将吡喹酮 (PZQ) 掺入自乳化药物递送系统 (SEDDS) 制剂中，以证明增加的表观溶解度和溶出速率可增强肠道渗透性。

方法

PZQ在脂质赋形剂和亲水性物质中的溶解度测量；用 PZQ 显示溶解度增加的辅料构建三元相图。通过扫描和透射电子显微镜对 SEDDS 制剂的球大小、多分散指数、zeta 电位、自乳化时间和形态进行表征。通过在离体模型中进行体外溶出曲线和渗透曲线来评估制剂。

结果

确定了四种 SEDDS 制剂，它们将吡喹酮的表观溶解度提高了 60-150 倍。获得的分散尺寸 < 350 nm，多分散指数值 < 0.3，分散时间 < 60 s，zeta 电位值 < -25 mV。与参考药物产品相比，PZQ 溶出度显着增加。将渗透曲线调整为一级动力学模型，SEDDS 制剂的表观吸收速率常数 (K _ab ) 比 PZQ 粉末高 18 倍，而表观渗透率 (P _app ) 和有效肠道渗透率 (与 PZQ 粉末相比，SEDDS 配方的P _eff ) 值增加了 18 倍。

结论

将 PZQ 掺入 SEDDS 增加了其表观溶解度和溶出速率，这些变化显着增强了肠道通透性的过程。此行为可用于支持属于生物制药分类系统 IV 类的药物配方。