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Systematic Development Of Sertraline Loaded Solid Lipid Nanoparticle (SLN) By Emulsification-ultrasonication Method And Pharmacokinetic Study In Sprague-Dawley Rats.

Md Akhlaquer Rahman, R. K. Harwansh, Z. Iqbal
Published 2019 · Chemistry, Medicine

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In the current research (i) solid lipid nanoparticles (SLN) were systematically developed by emulsification-ultrasonication method, and (ii) pharmacokinetic parameters were obtained after oral administration of a single dose of optimized SLN formulation and aqueous suspension of sertraline. Different batches were prepared by changing process parameters, and finally on the basis of nanoparticle size, size distribution i.e. polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and drug loading capacity (L) an optimum system was designed. 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. SLNs 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 encapsulation 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. 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.
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