Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Medicinal Chemistry

Background:

• Chagas disease affects millions globally, with Benznidazole (BNZ) as the primary treatment.
• BNZ exhibits poor aqueous solubility and significant toxicity, limiting its therapeutic efficacy.
• Developing improved drug delivery systems for BNZ is crucial for effective Chagas disease management.

Purpose of the Study:

• To develop and characterize Benznidazole (BNZ) inclusion complexes (ICs) using randomly methylated-β-cyclodextrin (RMβCD).
• To evaluate binary systems (BS) of BNZ-RMβCD and ternary systems (TS) incorporating hydrophilic polymers.
• To assess the potential for industrial scale-up of optimized BNZ-RMβCD formulations.

Main Methods:

• Preparation of binary systems (BS) and ternary systems (TS) of BNZ with RMβCD.
• Inclusion complex formation using kneading method and characterization of solid systems.
• Evaluation of dissolution rate enhancement for BNZ in developed systems.

Main Results:

• Solid binary systems (BS) demonstrated a significant increase in dissolution rate (Q>80%).
• The kneading method at a 1:0.17 BNZ:RMβCD ratio yielded optimal solid ICs (77.8% in 60 min).
• Ternary systems with hydroxypropylmethylcellulose (HPMC) showed no significant advantage over binary ICs.

Conclusions:

• Randomly methylated-β-cyclodextrin (RMβCD) is effective in enhancing BNZ dissolution and can be used for oral drug delivery.
• The kneading method is suitable for developing solid oral pharmaceutical products of BNZ-RMβCD.
• Cyclodextrin complexation offers a viable approach for standardized and safer Benznidazole drug delivery.