(189z) Enhancing the Long-Term Storage Stability of Amorphous Drug-Polyelectrolyte Nanoparticle Complex Via Incorporation of Hypromellose

Enhancing the Long-Term Storage
Stability of Amorphous Drug-Polyelectrolyte Nanoparticle Complex via Incorporation
of Hypromellose

By

Kunn Hadinoto and
Chew Jia Wei

Associate
Professor

School of Chemical
and Biomedical Engineering

Nanyang Technological
University

Singapore

Various solubility
enhancement strategies of BCS Class II and IV drugs have been proposed, for
example, by nanonization, amorphization, cyclodextrin inclusion, and
complexation/conjugation with each of them come with its pros and cons.
Recently, our group developed a new strategy of combined amorphization and
nanonization via electrostatically driven drug-polyelectrolyte complexation to
produce amorphous drug nanoparticle complex (or nanoplex in short) exhibiting
solubility enhancement capability. This strategy is highly attractive owed to
(1) its simple preparation involving only the mixing of drug and
polyelectrolyte solutions under ambient condition, (2) high drug utilization
rate without the need of solvent denoting its high mass and energy
sustainability. The amorphous drug-polyelectrolyte nanoplex, however, exhibit
poor physical stability during long-term storage in which the amorphous state
crystallizes, hence the solubility enhancement is lost. In this talk, a new
formulation strategy in which a well-known crystallization inhibitor,
hypromellose, is incorporated into the drug-polyelectrolyte nanoplex is
discussed using two model poorly-soluble drugs, i.e. curcumin and
ciprofloxacin. The amorphous ternary nanoplex was formed based on
electrostatic, hydrophobic, and hydrogen bond interactions among the drug,
polyelectrolyte, and hypromellose molecules. The results showed that the
incorporation of hypromellose successfully enhance the long-term stability of
the drug nanoplex (> 12 months) while at the same time prolong the
supersaturation generation in vitro, resulting in high and prolonged apparent
drug solubility. The inclusion of hypromellose, nevertheless, resulted in a
decrease in the drug payload and larger nanoparticle size with lower zeta
potential due to the non-ionic nature of hypromellose, in contract to the
charged nature of the polyelectrolytes. The variations in the drug payload and
nanoplex characteristics, nevertheless, did not influence its dissolution
characteristics or its storage stability. These results established the
amorphous drug nanoplex as an effective bioavailability enhancement strategy of
poorly soluble drugs.