Lipid-Based Formulation of Nateglinide as a Promising Strategy for Managing Solubility Challenges in Type II Diabetes Therapy: A SMEDDS Approach
Keywords:
Nateglinide, Solid SMEDDS, Oral bioavailability, Box-Behnken design, Dissolution enhancementAbstract
The present study focuses on the development and optimization of a solid self-microemulsifying drug delivery system (S-SMEDDS) of Nateglinide, a poorly water-soluble antidiabetic drug, to enhance its oral bioavailability. Initially, a liquid SMEDDS was formulated using Capmul MCM as the oil phase, Tween 80 as the surfactant, and Transcutol P as the co-surfactant, selected based on solubility studies and pseudo-ternary phase diagrams. The optimized liquid SMEDDS was subsequently solidified using Neusilin US2 as an adsorbent to obtain a free-flowing solid formulation. A Box-Behnken design was employed to systematically study the influence of three independent variables—Neusilin US2, Aerosil 200, and magnesium stearate-on critical formulation parameters including angle of repose, Carr’s index, and drug release. The optimized S-SMEDDS exhibited excellent micromeritic properties (angle of repose: 23.6° ± 0.2; Carr’s index: 13.7 ± 0.3; Hausner’s ratio: 1.13 ± 0.01), and demonstrated significantly enhanced in vitro drug release (98.7% within 30 minutes) compared to the pure drug. Solid-state characterization (FTIR, DSC, XRD, SEM) confirmed the transformation of Nateglinide into an amorphous state and its uniform distribution within the carrier matrix. These findings highlight the potential of S-SMEDDS as a promising strategy to improve the dissolution and oral absorption of poorly soluble drugs like Nateglinide
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