Formulating low-dose APIs, especially micronized or sensitive compounds, brings unique challenges in maintaining stability and ensuring uniformity. Here are some advanced solutions to tackle common issues like API loss during mixing and assay degradation:
Choosing the Right Filler
Optimal fillers like microcrystalline cellulose (MCC) help distribute low-dose APIs evenly, reducing segregation. Testing various filler grades is essential to balance flow and uniformity.
Minimizing API Loss in Mixing Bags
Use anti-static or low-static bags to prevent API from sticking to the surface. Consider rinsing bags after mixing to capture any residual API and reduce transfer losses.
Maintaining Equipment Cleanliness
In low-dose formulations, even trace residues can affect results. Strict cleaning protocols after each step help maintain consistency and prevent cross-contamination.
Optimizing Process Parameters for Direct Compression:
Adjusting blending time, speed, and compression force helps maintain homogeneity and stability, especially for fragile APIs.
Handling Micronized APIs with Granulation
Wet granulation can bind micronized APIs into stable granules, reducing segregation and improving distribution within the mix.
Controlling Environmental Factors
Managing humidity and temperature in the manufacturing area is crucial, especially for moisture-sensitive APIs and excipients.
Strengthening Quality Control
Regular in-process testing and representative sampling ensure that assay results accurately reflect the batch quality.
By implementing these strategies, pharmaceutical teams can enhance formulation robustness, minimize API loss, and maintain consistent product quality.
Read also:
