Background: Self-nanoemulsifying drug delivery system (SNEDDS) has immense potential
in oral bioavailability enhancement of lipophilic drugs.
Objective: This investigation involves the development of thermodynamically stable and dilutable
SNEDDS for tolbutamide, for achieving higher water solubility and enhanced dissolution rate which
in turn improves its oral bioavailability.
Method: Preliminary solubility studies were carried out and pseudo-ternary phase diagrams were plotted
for selection of best ratio of surfactant and co-surfactant. The drug loaded SNEDDS were prepared,
characterized w.r.t. refractive index, viscocity, globule size, zeta potential, and TEM, and converted
into solid self-nanoemulsifying granules (SSNEGs). These were further characterized and their
antidiabetic efficacy in male Wistar rats was evaluated.
Results: Solubility studies suggested the suitability of oleic acid as lipid phase; Tween 20 and PEG
400 as optimal surfactant and co-surfactant, respectively for formulation of SNEDDS formulations.
The optimal SNEDDS formulation having mean globule diameter, viscosity, polydispersity 58.55 ±
0.2 nm, 26.18 ± 0.2 cps, 0.277 respectively, and infinite dilution capability displayed a highly significant
increase in dissolution rate within 5 h compared to pure drug suspension. The SSNEGs showed
1.54 fold increase in drug dissolution rate compared to pure drug. Stability studies revealed no significant
change in morphology and globule size. Anti-hyperglycemic activity of tolbutamide loaded
SSNEGs in rats showed a significant reduction in elevated blood glucose level with absence of ketone
and glucose in urine.
Conclusion: The present study demonstrates a successful development of SNEDDS formulation with
an overall potential of bioavailability enhancement for tolbutamide, a BCS-II drug.