Amorphization of Albendazole Using Organic Acid-based Solid Dispersions for Improved Dissolution: A Solvent-free...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Formulation Development

Background:

• Albendazole (ABZ) has poor aqueous solubility and low oral bioavailability (<5%), limiting its therapeutic efficacy.
• Enhancing ABZ dissolution is crucial for improving its clinical effectiveness.

Purpose of the Study:

• To develop a solvent-free strategy for enhancing albendazole dissolution using solid dispersions (SDs) with organic acids.
• To investigate the impact of citric acid (CA), tartaric acid (TA), and glutaric acid (GA) on ABZ solubility and solid-state properties.

Main Methods:

• Formulation of ABZ-organic acid solid dispersions using concentrated acid solutions and drying.
• pH-dependent solubility studies, Powder X-ray Diffraction (PXRD), FTIR, and solution-phase 1H NMR for characterization.
• Step dissolution studies and stability testing under accelerated conditions (40°C/75% RH).

Main Results:

• Citric acid (CA) enhanced ABZ solubility by 188,000-fold; complete amorphization of ABZ was observed in CA-based SDs at 1:1 molar ratio and higher.
• Hydrogen bonding between ABZ and CA stabilized the amorphous form and supersaturation.
• CA-based SDs achieved 100% cumulative percentage drug dissolved (CPDD) in 0.1 N HCl; TA-based SDs reached up to 80% CPDD.

Conclusions:

• A cost-effective, scalable, solvent-free method using organic acids (especially CA) effectively enhances ABZ dissolution and stability.
• The developed solid dispersions show potential for improving the oral bioavailability of poorly soluble drugs like albendazole.
• This approach offers a promising strategy for formulating other challenging hydrophobic drugs.