Seasons PowerPoint

European Pharmacopoeia -ph. Eur.- Monograph Tablets -0478- | Essential |

  • Assay / Content of active ingredient
  • Content uniformity / Uniformity of dosage units
  • Dissolution
  • Disintegration
  • Mechanical properties
  • Impurities and degradation products
  • Microbial quality
  • Packaging, labeling, storage

    • The monograph sets GMP-related principles for manufacture:

    The majority of Monograph 0478 is dedicated to mandatory physical tests. Failure in any of these three categories results in batch rejection. European Pharmacopoeia -ph. Eur.- Monograph Tablets -0478-

    For many tablets, disintegration is not enough; the drug must dissolve to be absorbed. Dissolution testing measures the rate and extent of drug release into a medium under controlled conditions (apparatus 1: Basket, or apparatus 2: Paddle). Assay / Content of active ingredient

    Tablets are solid preparations each containing a single dose of one or more active substances. They are obtained by compressing uniform volumes of particles or by another suitable manufacturing process (e.g., compaction, granulation followed by compression). Content uniformity / Uniformity of dosage units

    While the global industry tries to harmonize via the ICH Q4B process, differences remain.

    | Parameter | Ph. Eur. 0478 | USP <701>/<711> | JP (General Tests) | | :--- | :--- | :--- | :--- | | Disintegration time (uncoated) | 15 min | 15 min (but often 30 min for large tabs) | 15 min | | Dissolution vessel volume | 900 mL (preferred) | 500, 900, or 1000 mL | 900 mL | | Friability acceptance | 1.0% (uncoated) | 1.0% (but 0.8% for high-use) | 1.0% | | Uniformity of dosage units | AV ≤ 15.0 (2.9.40) | AV ≤ 15.0 (identical via ICH Q4B) | AV ≤ 15.0 |

    Critical difference: Ph. Eur. 0478 allows a "re-test" for disintegration (repeat on 6 new tablets) if 1-2 of the first 6 fail. USP <701> requires that if 1-2 fail, you test 12 more; if more than 2 fail initially, rejection is immediate.