Unsatisfied processing conditions in making ifosfamide nanostructured lipid carriers: Effects of various formulation parameters on particle size, entrapment efficiency, and drug loading capacity

Abstract

Introduction: The objectives of the present investigation were to develop an optimized
formulation of ifosfamide (IF) nanostructured lipid carrier (NLC) to sustain the
release, to overcome the instability of the drug in an acidic environment during oral
administration, drug leakage during storage, drug expulsion, and low drug loading (DL).
Materials and Methods: The IF NLC was prepared by solvent diffusion technique.
Response surface methodology was applied to optimize the formulation. Drug/lipid
ratio, organic/aqueous phase ratio, and concentration of surfactant were considered as the
formulation variables that mainly affects the particle size (PS), entrapment efficiency (EE)
and DL of the NLC. A total of 20 sets of formulations were performed with different
ratios of drug/lipid, organic/aqueous phase volume and various concentration of the
surfactant. The formulation was evaluated for PS, EE, and DL, differential scanning
calorimetry, Fourier transform infrared and in vitro dissolution. Results: Increasing the
aqueous phase volume results in an increase of EE and a decrease in loading capacity.
PS also decreases to extent. Increasing the lipid concentration, EE increases and as well
the PS. An increase in the concentration of the surfactant resulted in a decrease in PS and a
slight increase in encapsulation efficiency and loading capacity. Conclusion: The positive
impact on the response variables (PS, EE and DL capacity) of the formulation of IF
NLC would be obtained only if the processing conditions could be followed.