Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation.

Spandana Inugala, Basanth Babu Eedara, Sharath Sunkavalli, Rajeshri Dhurke, Prabhakar Kandadi, Raju Jukanti, Suresh Bandari

文献索引：Eur. J. Pharm. Sci. 74 , 1-10, (2015)

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摘要

The current study was aimed to investigate the potential of solid self-nanoemulsifying drug delivery system (S-SNEDDS) composed of Capmul MCM C8 (oil), Tween 80 (surfactant) and Transcutol P (co-surfactant) in improving the dissolution and oral bioavailability of darunavir. Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were developed by using rational blends of components with good solubilizing ability for darunavir which were selected based on solubility studies, further ternary phase diagram was constructed to determine the self-emulsifying region. The prepared L-SNEDDS formulations were evaluated to determine the effect of composition on physicochemical parameters like rate of emulsification, clarity, phase separation, thermodynamic stability, cloud point temperature, globule size and zeta potential. In vitro drug release studies showed initial rapid release of about 13.3 ± 1.4% within 30 min from L-SNEDDS followed by slow continuous release of entrapped drug and reached a maximum of 62.6 ± 3.5% release at the end of 24h. The globule size analysis revealed the formation of nanoemulsion (144 ± 2.3 nm) from the optimized L-SNEDDS formulation and was physically adsorbed onto neusilin US2. In vitro dissolution studies indicated faster dissolution of darunavir from the developed S-SNEDDS with 3 times greater mean dissolution rate (MDR) compared to pure darunavir. Solid state studies concluded the presence of drug in non-crystalline amorphous state without any significant interaction of drug with the components of S-SNEDDS. Furthermore, in vivo pharmacokinetic studies in Wistar rats resulted in enhanced values of peak drug concentration (Cmax) for L-SNEDDS (2.98 ± 0.19 μg/mL) and S-SNEDDS (3.7 ± 0.28 μg/mL) compared to pure darunavir (1.57 ± 0.17 μg/mL).Copyright © 2015 Elsevier B.V. All rights reserved.