Overcoming poor tabletability of pharmaceutical crystals by surface modification.

PURPOSE: To test the hypothesis that coating particles with a highly bonding polymer is effective in improving tabletability of poorly compressible drugs.

METHODS: Micronized acetaminophen (d (90) < 10 μm, Form I) was coated with 1%-10% (wt%) hydroxypropyl cellulose (HPC) by spray-drying. Phase nature of acetaminophen powders was identified using powder X-ray diffractometry, SEM, and thermal analysis. Powder tabletability was evaluated on a compaction simulator. Mechanical properties of acetaminophen and HPC were determined by nanoindentation.

RESULTS: Spray-drying successfully produced acetaminophen particles enveloped with a layer of HPC but did not cause any detectable phase change of acetaminophen. At 200 MPa, physical mixtures containing up to 40% HPC could not be compressed into intact tablets. In contrast, acetaminophen coated with 1% to 10% HPC could form strong tablets (tensile strength was 1.9-7.0 MPa) at 200 MPa. Under a given compaction pressure, tablet tensile strength increased sharply with the amount of HPC coating. The profoundly improved tabletability of acetaminophen confirmed the effectiveness of the particle coating approach in improving tableting performance of drugs.

CONCLUSIONS: HPC coating by spray-drying profoundly enhances tabletability of acetaminophen. This strategy is expected to have transformative effects on formulation development of poorly compressible drugs.