采用乳化-超声法系统研制舍曲林负载固体脂质纳米粒（SLN）及其在Sprague-Dawley大鼠中的药代动力学研究。

Systematic Development of Sertraline Loaded Solid Lipid Nanoparticle (SLN) by Emulsification-Ultrasonication Method and Pharmacokinetic Study in Sprague-Dawley Rats.

作者信息

Rahman Mohammad A, Harwansh Ranjit K, Iqbal Zeenat

机构信息

College of Pharmacy, Taif University, Haweiya, Taif-21974, Saudi Arabia.

Faculty of Pharmacy, Integral University, Kursi Road, Lucknow-226022, India.

出版信息

Pharm Nanotechnol. 2019;7(2):162-176. doi: 10.2174/2211738507666190327145628.

DOI:10.2174/2211738507666190327145628

PMID:30919786

Abstract

OBJECTIVE

To circumvent the aforementioned problems and for the successful delivery of those newly discovered poorly soluble compounds, researchers have focused on the feasibility of biocompatible lipids such as Solid lipid nanoparticles (SLN) as carrier system.

BACKGROUND

Sertraline (SRT) is commercially available as hydrochloride salt. Poor bioavailability (around 44%) of hydrochloride salt is considered to be conversion of salts to free base in the gastrointestinal tract which retard it's absorption.

METHODS

Different batches of solid lipid nanoparticles (SLN) were prepared and on the basis of particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and drug loading capacity (L) an optimum system was designed.

RESULTS

The optimized formulation contains; 5% (w/v) Compritol® E ATO as lipids, 2.5% (w/v) Tween® 80 as surfactant and 0.1% (w/v) SRT as actives. The formulation was freeze-dried using mannitol as a cryoprotectant to control the aggregation of particles during redispersion process. SLN with <110 nm size, <0.2 PDI, >36 mV ZP, >72% EE, and nearly 0.7% L can be formed at appropriate formulation process conditions; homogenization time (HT) and sonication time (ST) at 5 min and 10 min, respectively. XRD studies indicated the presence of amorphous form of drug that is completely encapsulated within the nanoparticulate matrix system. The optimized SLN formulation have shown the highest value of zeta potential (-36.5 mV) confers stability of nanodispersion. Release of drug encapsulated in SLN showed a biphasic pattern and was extended upto 12 hours. The maximum plasma concentration (Cmax) and area under the curve (AUC) in case of sertraline loaded SLN were found 10-fold and 6-fold higher, respectively compared to pure drug.

CONCLUSION

The result depicted enhanced extent of absorption of sertraline from SLN compared to plain sertraline. Furthermore, sertraline-loaded SLN were found to be stable at 4°C for 6 months of study period. Hence, the SLN can be used as a potential carrier for successful delivery of poorly water-soluble drugs associated with poor oral bioavailability like sertraline.

摘要

目的

为规避上述问题并成功递送那些新发现的难溶性化合物，研究人员聚焦于生物相容性脂质如固体脂质纳米粒（SLN）作为载体系统的可行性。

背景

舍曲林（SRT）以盐酸盐形式上市。盐酸盐的生物利用度较差（约44%），被认为是由于盐在胃肠道中转化为游离碱，从而阻碍了其吸收。

方法

制备不同批次的固体脂质纳米粒（SLN），并基于粒径、多分散指数（PDI）、zeta电位（ZP）、包封率（EE）和载药量（L）设计出最佳体系。

结果

优化后的制剂包含：5%（w/v）Compritol® E ATO作为脂质，2.5%（w/v）吐温® 80作为表面活性剂，0.1%（w/v）SRT作为活性成分。该制剂以甘露醇作为冷冻保护剂进行冻干，以控制再分散过程中颗粒的聚集。在适当的制剂工艺条件下，即均质时间（HT）和超声时间（ST）分别为5分钟和10分钟时，可形成粒径<110 nm、PDI<0.2、ZP>36 mV、EE>72%且载药量接近0.7%的SLN。X射线衍射（XRD）研究表明存在药物的无定形形式，其完全包封在纳米颗粒基质系统内。优化后的SLN制剂显示出最高的zeta电位值（-36.5 mV），赋予了纳米分散体稳定性。包封在SLN中的药物释放呈现双相模式，且延长至12小时。与纯药物相比，载有舍曲林的SLN的最大血浆浓度（Cmax）和曲线下面积（AUC）分别高出10倍和6倍。