Page 75 - Pharmaceutics III_ 02-06-01304_Fall 2025_ Pharm D_Electronic book
P. 75
o Reduce pressure.
3. Tablet discolors:
o Oxidation or Maillard reaction (lactose + amine).
o Use alternative excipient or antioxidants.
4. Capsule leaks:
o Overfilled or cracked shell.
o Adjust fill weight or replace shell.
Tablet Core Formulation Development:
Design Considerations:
• Dose, solubility, compressibility, stability.
• Choice of diluent, binder, disintegrant, lubricant based on compatibility.
Preformulation Studies:
1. Drug–excipient compatibility (DSC, FTIR).
2. Flow properties.
3. Moisture sensitivity.
4. Compressibility index.
Compatibility Testing:
• Drug and excipient mixtures stored at 40°C / 75 % RH for 1 month.
• Assay and physical observation performed.
Interpretation:
• No color change or degradation = compatible.
• Degradation peaks = incompatibility → use alternative excipient.
Tablet Scale-Up (Process Optimization):
• Maintain same shear, dwell time, and granule density as pilot scale.
• Use similarity factor (f₂) to compare dissolution profiles.
Critical Parameters:
• Lubricant blending time.
• Granule moisture content.
74
