If blend uniformity (BU) is passing but content uniformity (CU) is failing, it suggests that the blend is initially uniform but becomes inconsistent during manufacturing. Key causes and solutions include:
Causes
1. Segregation: Differences in particle size, density, or shape lead to separation during transfer or filling.
2. Poor Flow Properties: Uneven filling due to flow issues.
3. Over-Lubrication: Excessive post-lubrication mixing causes segregation.
4. API Particle Size Variability: Large differences in API particle size cause uneven distribution.
5. Weight Variability: Inconsistent die or capsule filling during compression.
6. Static Charge: API particles stick to equipment due to static.
7. Improper Granulation: Uneven granule size or fines lead to segregation.
Solutions
1. Blending and Handling: Optimize blending times, minimize transfer steps, and avoid over-mixing.
2. Flow Improvement: Add glidants (e.g., colloidal silicon dioxide) and optimize particle size.
3. Granulation: Ensure uniform granules and avoid excessive drying or fines.
4. Post-Lubrication: Mix lubricants minimally to prevent segregation.
5. Equipment Optimization: Calibrate and validate filling and compression machines regularly.
6. Static Control: Ground equipment and control humidity.
7. In-Process Testing: Frequently check weight and CU during production.
By addressing segregation, flow, and process variability, CU failures can be mitigated without impacting BU.
Read also:
- Blend Uniformity Analysis
- Differences Among Blend Uniformity, Content Uniformity and Weight Variation
