Drug-Lipid-Surfactant Miscibility for the Development of Solid Lipid Nanoparticles

Abstract

This research aimed to study the correlation between miscibility of flutamide (FLT), lipids and surfactant on the particle size of solid lipid nanoparticles (SLNs). Physical mixtures (PMs) of lipids-glyceryl monooleate (GMO), Precirol® (glyceryl palmitostearate, PRE), glyceryl monostearate (GMS), and Compritol® (glyceryl dibehenate, COM) were prepared with surfactant-Gelucire® (stearoyl polyoxyl-32 glycerides, GEL) 50/13 and 44/14. PMs were prepared in 5:2 w/w ratio (lipid:surfactant) and 2:1 w/w (Flutamide (FLT):lipids/GEL 50/13) by co-melting. Miscibility of PMs was investigated using modulated differential scanning calorimetry (MDSC). SLNs with and without drug were prepared using GEL 50/13 by the ultra-sonication method and particle size analysis was conducted. PMs of GMO, GMS, and PRE with both surfactants showed a decrease in the melting temperature, no change in melting and crystallization peak was observed with COM-GELs, indicating immiscibility. Similarly, MDSC data suggests good miscibility of FLT in GMO, GMS, and GEL 50/13 but not in PRE and COM. The particle size of drug-loaded SLNs prepared from GMO and GMS with GEL 50/13 was found to be 70.2 ± 5.4 and 92.6 ± 8.5 compared to > 200-nm particles obtained from PRE and COM. On lyophilization, an increase in particles size was observed with COM only. The particle size of SLNs with PRE and COM was prominently increased during stability studies indicating SLNs prepared with GMO and GMS are more stable due to miscibility and ability to reduce the crystallinity of FLT. The results established a good correlation between drug, lipids, and surfactants miscibility to the obtained particle size of SLNs before and after lyophilization.

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Correspondence to Harsh Chauhan.

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Trivino, A., Gumireddy, A. & Chauhan, H. Drug-Lipid-Surfactant Miscibility for the Development of Solid Lipid Nanoparticles. AAPS PharmSciTech 20, 46 (2019). https://doi.org/10.1208/s12249-018-1229-3

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KEY WORDS

  • solid lipid nanoparticles
  • miscibility
  • flutamide
  • lipids