Formulation, Characterization, and Evaluation of Eudragit-Coated Saxagliptin Nanoparticles Using 3 Factorial Design...

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Drug Delivery Systems

Background:

• Saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is used for Type 2 Diabetes Mellitus (T2DM).
• Low oral bioavailability is a significant limitation of Saxagliptin therapy.
• Enhancing drug delivery is crucial for effective T2DM management.

Purpose of the Study:

• To enhance the oral bioavailability of Saxagliptin.
• To develop enteric-coated Solid Lipid Nanoparticles (SLNs) for controlled drug release.
• To optimize SLN formulation using a Central Composite Design (CCD).

Main Methods:

• Saxagliptin SLNs were prepared using a modified solvent injection technique with Eudragit RS100 enteric coating.
• A Central Composite Design (CCD) was employed to optimize lipid, polymer, surfactant concentration, and homogenization speed.
• Formulations were evaluated for particle size, Zeta potential, PDI, drug loading, entrapment efficiency, in-vitro release, and in-vivo pharmacokinetics.

Main Results:

• Optimized SLNs exhibited particle sizes between 212-442 nm with good stability (Zeta potential: -41.09 to +30.86 mV) and uniformity (PDI: 0.26-0.45).
• In-vivo pharmacokinetic studies demonstrated a significant enhancement in Saxagliptin oral bioavailability.
• The developed reversed-phase HPLC method was specific, robust, and accurate for drug quantification.

Conclusions:

• Developed and optimized Saxagliptin SLNs significantly improve oral bioavailability compared to the native drug.
• Enteric coating of SLNs with Eudragit RS100 is a promising strategy for enhanced drug delivery.
• This formulation approach holds potential for improved Type 2 Diabetes Mellitus therapy.