In generic drug development, achieving the desired dissolution profile is critical — especially for regulatory bioequivalence. Surprisingly, it’s not always necessary to reformulate. Strategic modifications in process parameters alone can significantly enhance performance, stability, and compliance with RLD benchmarks.
Here’s how process optimization can do the trick
Key Manufacturing Parameters That Influence Dissolution:
1. Order and Stage of Addition
The sequence in which the API and excipients are added affects the uniformity of the blend and the resulting dissolution behavior.
2. Distribution of Disintegrants (Intra- vs. Extra-granular)
Balancing intra-granular and extra-granular disintegrants — and controlling their blending time — is critical for optimal disintegration and drug release.
3. Lubricant Blending Time
Over-lubrication can lead to hydrophobic surfaces that slow dissolution. A typical optimal blending time is 3 to 5 minutes, especially with Y-cone blenders.
4. Granule Moisture Content
Moisture above 2.0–2.5% results in hard tablets that disintegrate slowly and perform poorly over time. Drying to optimal moisture improves consistency.
5. Use of Dry Starch NF at Lubrication Stage
Adding Dry Starch NF during the lubrication step can enhance dissolution by partially coating the lubricant, improving wettability.
6. Binder Addition Strategy (Dry vs. Solution)
The choice between dry mix and solution form of binders like PVP K30 affects granule structure and tablet porosity.
7. Premixing Glidant and Lubricant
Preparing a premix prevents uneven coating of granules and improves powder flow, aiding uniform compression.
8. Excipient Selection and Functionality
Properties of non-actives, such as bulk density and particle size, have direct influence on dissolution and compressibility.
Practical Outcome:
By managing these parameters effectively, formulators can:
- Improve batch-to-batch uniformity
- Enhance dissolution without changing the API/excipient ratio
- Ensure compliance with bioequivalence criteria
- Reduce post-approval variation risks
This reflects the growing importance of process knowledge and control in pharmaceutical product development. Success isn't always about what’s inside the formula — sometimes, it's how you put it together that makes all the difference.
This approach emphasizes that pharmaceutical development is not only about "what" we formulate — but also "how" we manufacture. A deep understanding of process science can often solve dissolution problems more elegantly than reformulating a product from scratch.
As regulatory agencies shift toward Quality by Design (QbD) and lifecycle management, this level of process awareness will be indispensable for successful, cost-effective, and scalable drug development.
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