Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular...

Area of Science:

• Pharmaceutical Chemistry
• Supramolecular Chemistry
• Drug Delivery Systems

Background:

• Sulfadiazine (SDZ) is an important antibiotic, but its low water solubility limits its therapeutic applications.
• Cyclodextrins, particularly 2-hydroxypropyl-beta-cyclodextrin (HPBCD), are widely used to enhance the solubility and bioavailability of poorly soluble drugs.
• Understanding the inclusion complexation mechanism is crucial for optimizing drug formulation and efficacy.

Purpose of the Study:

• To prepare and characterize an inclusion complex between sulfadiazine (SDZ) and 2-hydroxypropyl-beta-cyclodextrin (HPBCD).
• To investigate the effect of HPBCD complexation on the water solubility of SDZ.
• To elucidate the inclusion mode and binding interactions between SDZ and HPBCD.

Main Methods:

• Preparation and characterization of the SDZ-HPBCD inclusion complex.
• Phase-solubility studies to determine drug solubility and binding constants.
• 2D NMR (ROESY) spectroscopy to investigate the inclusion geometry.
• Molecular modeling using semiempirical PM6 and RM1 methods to confirm the complex structure.

Main Results:

• The phase-solubility diagram indicated an increase in the water solubility of sulfadiazine upon complexation with HPBCD.
• A binding constant of 1879 M⁻¹ was calculated, signifying moderate binding affinity.
• 2D NMR (ROESY) data and molecular modeling consistently suggested an NH(2)-in orientation of SDZ within the HPBCD cavity.
• The semiempirical PM6 and RM1 methods corroborated the proposed inclusion complex structure.

Conclusions:

• The formation of a sulfadiazine-HPBCD inclusion complex effectively enhances the water solubility of sulfadiazine.
• The inclusion complexation occurs with a specific orientation of the drug molecule within the cyclodextrin cavity.
• This study provides valuable insights into the supramolecular interactions governing SDZ-HPBCD complexation, relevant for pharmaceutical formulation development.