Background: Metformin (MF) is an antidiabetic drug that belongs to class III of the biopharmaceutical
classification system (BCS) characterized by high solubility and low permeability.
Objective: The study aimed to prepare metformin as nanostructured lipid carriers (MF-NLCs) to
control the drug release and enhance its permeability through the biological membrane.
Methods: 22 full factorial design was used to make the design of MF-NLCs formulations. MFNLCs
were prepared by hot-melt homogenization-ultra sonication technique using beeswax as
solid lipid in the presence of liquid lipid (either capryol 90 or oleic acid) and surfactant (either
poloxamer 188 or tween 80).
Results: The entrapment efficiency (EE%) of MF-NLCs was ranged from 85.2±2.5 to 96.5±1.8%.
The particle size was in the nanoscale (134.6±4.1 to 264.1±4.6 nm). The value of zeta potential has
a negative value ranged from -25.6±1.1 to -39.4±0.9 mV. The PDI value was in the range of
0.253±0.01 to 0.496±0.02. The cumulative drug release was calculated for MF-NLCs and it was
found that Q12h ranged from 90.5±1.7% for MF-NLC1 to 99.3±2.8 for MF-NLC4. Infra-red (IR)
spectroscopy and differential scanning calorimetry (DSC) studies revealed the compatibility of the
drug with other ingredients. MF-NLC4 was found to be the optimized formulation with the best responses.
Conclusion: 22 full factorial design succeed to obtain an optimized formulation which controls the
drug release and increases the drug penetration.