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.