1 research outputs found
Structural Modifications of Polyethylenimine to Control Drug Loading and Release Characteristics of Amorphous Solid Dispersions
Crystalline
drugs with low solubility have the potential to benefit
from delivery in the amorphous form. The polymers used in amorphous
solid dispersions (ASDs) influence their maximum drug loading, solubility,
dissolution rate, and physical stability. Herein, the influence of
hydrophobicity of crosslinked polyethylenimine (PEI) is investigated
for the delivery of the BCS class II nonsteroidal anti-inflammatory
drug flufenamic acid (ffa). Several synthetic variables for crosslinking
PEI with terephthaloyl chloride were manipulated: solvent, crosslinking
density, reactant concentration, solution viscosity, reaction temperature,
and molecular weight of the hyperbranched polymer. Benzoyl chloride
was employed to cap amine groups to increase the hydrophobicity of
the crosslinked materials. Amorphous deprotonated ffa was present
in all ASDs; however, the increased hydrophobicity and reduced basicity
from benzoyl functionalization led to a combination of amorphous deprotonated
ffa and amorphous neutral ffa in the materials at high drug loadings
(50 and 60 wt %). All ASDs demonstrated enhanced drug delivery in
acidic media compared to crystalline ffa. Physical stability testing
showed no evidence of crystallization after 29 weeks under various
relative humidity conditions. These findings motivate the broadening
of polymer classes employed in ASD formation to include polymers with
very high functional group concentrations to enable loadings not readily
achieved with existing polymers