Background: Supersaturable SMEDDS, a versatile dosage form, was investigated for improving
the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug
Objective: The present research pursues the development of efavirenz loaded Supersaturable Self-
Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance.
Methods: Preformulation studies were carried out to determine the optimized range of lipid excipients
to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared
by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS
SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies
and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to
simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through
in vivo pharmacokinetics approach.
Results: The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P
exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing
suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro
supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular
interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in
biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However,
in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed
conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant
increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed
Conclusion: The designed delivery system indicated promising results in developing an effectual EFV
formulation for HIV treatment.
Keywords: Efavirenz, SMEDDS, biorelevant media, food effect, absorption, HIV, BCS.
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