Abstract:
Supersaturated drug delivery system (SDDS)
enables the solubility and sustained membrane transport of poorly
water-soluble drugs. SDDS provides higher drug concentration in
the dispersed phase and equilibrium in the continuous phase,
which corresponds to amorphous solubility of the drug. Rifaximin
(RFX) is a nonabsorbable BCS class IV drug approved for the
treatment of irritable bowel syndrome and effective against
Helicobacter pylori. RFX shows slow crystallization and precipitation in an acidic pH of 1.2−2, leading to obliteration of its
activity in the gastrointestinal tract. The objective of the present
study is to inhibit the precipitation of RFX, involving screening of
polymers at different concentrations, using an in-house developed
microarray plate method and solubility studies which set forth
hydroxypropyl methylcellulose (HPMC) E15, Soluplus, and polyvinyl alcohol to be effective precipitation inhibitors (PIs). Drug−
polymer precipitates (PPTS) are examined for surface morphology by scanning electron microscopy, solid-phase transformation by
hot stage microscopy, the nature of PPTS by polarized light microscopy, and drug−polymer interactions by Fourier transform
infrared and nuclear magnetic resonance spectroscopy. Besides, the unfathomed molecular mechanism of drug−polymer interplay is
discerned at the air−water interface using sum-frequency generation spectroscopy to correlate the interfacial hydrogen bonding
properties in bulk water. Surprisingly, all studies disseminate HPMC E15 and Soluplus as effective PIs of RFX.
