Ternary Amorphous Solid Dispersions Containing a High-Viscosity Polymer and Mesoporous Silica Enhance Dissolution...

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Materials Science

Background:

• Achieving sustained drug supersaturation is crucial for enhancing the bioavailability of poorly soluble drugs.
• Traditional amorphous solid dispersions (ASDs) often face challenges in maintaining supersaturation, especially at high drug loadings.
• Itraconazole (ITZ), a poorly soluble antifungal agent, requires advanced formulation strategies to improve its therapeutic efficacy.

Purpose of the Study:

• To evaluate the benefits of a ternary amorphous solid dispersion (ASD) designed as an immediate-release tablet with a high drug load (40% w/w).
• To assess the ability of the ternary ASD to maintain drug supersaturation during dissolution testing.
• To explore the application of hot melt extrusion (HME) for manufacturing high-drug-load ASD tablets with improved dissolution.

Main Methods:

• Ternary ASD granules were prepared using hot melt extrusion (HME) with itraconazole (ITZ) 50%, hypromellose (HPMC) 20% (AF4M), and mesoporous silica (XDP) 30%.
• The ternary ASD granules were formulated into immediate-release tablets containing 40% w/w ITZ.
• Dissolution testing was performed in neutral pH media, and tablet properties (size, hardness, disintegration) were evaluated. High-resolution scanning electron microscopy (SEM) was used to analyze particle morphology.

Main Results:

• The ternary ASD granules containing high-viscosity HPMC (AF4M) demonstrated significantly enhanced drug supersaturation maintenance ability.
• The final ternary ASD tablets (40% ITZ) exhibited acceptable physical properties and dissolution behavior similar to the granules.
• Under neutral conditions, the ternary ASD tablets showed immediate and higher ITZ release compared to binary ASDs, attributed to nano-sized ITZ/AF4M particles formed during HME.

Conclusions:

• A ternary ASD formulation incorporating high-viscosity HPMC and mesoporous silica, manufactured via HME, enables the design of high-content, small-size tablets with ideal dissolution profiles.
• This technology facilitates enhanced drug supersaturation maintenance and immediate drug release, particularly beneficial for poorly soluble drugs like itraconazole.
• The developed HME-based ternary ASD manufacturing process shows promise for continuous manufacturing of advanced drug delivery systems.