Lipid-Based Formulation of Nateglinide as a Promising Strategy for Managing Solubility Challenges in Type II Diabetes Therapy: A SMEDDS Approach

Abstract

The present study focuses on the development and optimization of a solid self-microemulsifying drug delivery system (SSMEDDS) 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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Materials and Excipients

Nateglinide (NGN) was received as a gift sample from Aurobindo Pharma Ltd., Hyderabad, India. Oleic acid and ethyl oleate were procured from Alpha Chemicals Laboratories and SDFCL, Mumbai, respectively. Various oils including soybean oil, coconut oil, shark liver oil, linseed oil, sunflower oil, olive oil, arachis oil, castor oil, and clove oil were obtained from S.D. Fine Chemicals, Mumbai. All other chemicals used were of pharmaceutical or analytical grade. Excipients Screening The formulation of Self-Emulsifying Drug Delivery Systems (SEDDS) necessitates a systematic and scientifically rigorous selection of lipidic excipients, including oils, surfactants, and co-surfactants, to ensure spontaneous emulsification upon dilution in gastrointestinal fluids. The initial phase of development involved the quantitative determination of nateglinide (NGN) solubility in a range of pharmaceutically acceptable lipidic vehicles to identify excipients with optimal solubilizing capacity. This was followed by a comprehensive formulation screening process, wherein the miscibility and self-emulsification efficiency of various excipients combinations were evaluated under mild agitation conditions, simulating in vivo gastrointestinal motility. These preliminary assessments were integral to the rational design of a stable and efficient SEDDS capable of forming fine oil-in-water emulsions, thereby enhancing the dissolution rate and oral bioavailability of NGN [12, 13]

Sachin Bhaskarrao Dudhe, Santosh Ghule, Lalchand Devhare, Journal of Neonatal Surgery | Year: 2025 | Volume: 14 | Issue: 32s Sachin Bhaskarrao Dudhe, Santosh Ghule, (2025) Lipid-Based Formulation of Nateglinide as a Promising Strategy for Managing Solubility Challenges in Type II Diabetes Therapy: A SMEDDS Approach
January 2025Journal of Neonatal Surgery 14(32s):369-377