High Bulk-Density Amorphous Dispersions to Enable Direct Compression of Reduced Tablet Size Amorphous Dosage Units

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Amorphous solid dispersions (ASDs) enhance the bioavailability of poorly water-soluble drugs.
• Traditional ASD formulations often require excipients, leading to larger tablet sizes.
• Processing challenges associated with ASD material attributes necessitate innovative manufacturing approaches.

Purpose of the Study:

• To develop a novel manufacturing pathway for amorphous solid dispersions (ASDs) that overcomes formulation and processability challenges.
• To achieve high drug loading in directly compressed tablets, thereby reducing tablet size.
• To evaluate the pharmacokinetic performance of ASDs produced via the new method.

Main Methods:

• A combined co-precipitation and thin film evaporation (TFE) process was employed to create high bulk-density co-precipitated amorphous dispersions (cPAD).
• The cPAD/TFE material was directly compressed into tablets at high amorphous solid dispersion loadings (up to 89 wt%).
• Pharmacokinetic performance was assessed and compared to traditional spray-dried intermediate (SDI) formulations.

Main Results:

• The novel ASD manufacturing train produced cPAD with high bulk density, enabling direct compression.
• Tablets with up to 89 wt% ASD loading were achieved, resulting in over a 60% reduction in tablet size compared to SDI formulations.
• The TFE-isolated, co-precipitated dispersion demonstrated pharmacokinetic performance equivalent to SDI formulations.

Conclusions:

• A novel ASD manufacturing pathway combining co-precipitation and TFE facilitates high drug loading and significantly reduced tablet size.
• Direct compression of high-load ASDs is feasible with this method, overcoming previous formulation limitations.
• This approach offers downstream advantages for developing smaller, more patient-friendly dosage forms.