Indomethacin is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) that are
widely prescribed drug for pain and inflammation. However, its notoriety of causing
gastrointestinal effect, low water solubility, and its short half-life would affect patient
compliance and its oral absorption and accordingly justify the need to develop a formula
with a controlled and sustained release manner in combination with anti-ulcer
drugs. Herein, we synthesized indomethacin-paracetamol co-drug loaded in nanoemulsion
and encapsulated in famotiditine loaded polycaprolactone (PCL)
nanoparticles. The synthesis of the co-drug was achieved by the formation of a
hydrolyzable ester between the indomethacin and paracetamol. The synthesized codrug
was preloading in nanoemulsion (Co-NE), which encapsulated into famotidine
PCL nanoparticles utilizing the nanoprecipitation approach. The developed nanosystem
showed hydrodynamic size less than 200 nm and the zeta potential value
above −30 mV. TEM images confirmed the morphological structure of the formed
nanoemulsion and the loaded PCL nanoparticles. Stability studies revealed that the
developed nanosystem was stable at different temperatures and pHs over 1 month.
Moreover, improvement of the solubilities of these three drugs leading to have a
controlled-release multicomponent system of both co-drug and famotidine over
3 days. This multicomponent nanoparticle might be a potential platform to overcome
the obstacles of NSAIDs, synergize drugs with different mechanisms of actions by
co-encapsulating a small-sized nanoemulsion into PCL nanoparticles for reaching the
goal of effective anti-inflammatory therapy.

Title

Drug Development Research

Publisher

Wiley

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

1.902

Publication Type

Both (Printed and Online)

Volume

82

Year

2021

Pages

448-457