Developing oral tablets containing low-dose actives in the range of 1 to 10 milligrams is often most efficient through the direct compression route. Compared to wet granulation methods, direct compression offers reduced processing steps, cost savings, and faster development timelines.
Key advantages of direct compression development
1. Simplified process with no need for wet or dry granulation
2. Faster scale-up and technology transfer
3. Lower equipment and manpower requirements
4. Opportunity to use geometric blending for multiple strengths
5. Possibility of bioequivalence waiver for lower strengths based on dissolution similarity
Design strategy for direct compression formulations
1. Select an appropriate excipient system such as spray-dried lactose with microcrystalline cellulose or with co-processed materials
2. Use geometric proportioning to design multiple strengths from a common base blend. For example, a 10 milligram strength tablet can be created by doubling the 5 milligram blend
3. Choose suitable tablet weights based on drug load and manufacturability. For 1 to 5 milligram strength, the typical tablet weight ranges from 100 to 140 milligrams. For 6 to 10 milligram strengths, the weight can range from 200 to 280 milligrams
4. Define ideal tablet specifications. Tablet hardness should range from 5 to 9 kilopond units. Disintegration time should be less than 5 minutes. Friability should be less than 1 percent. Thickness should range from 2 point 5 to 4 millimeters. Rapid dissolution is essential for early drug release and absorption.
When to choose direct compression?
Direct compression is most suitable when the drug is compressible, non-hygroscopic, and stable in direct-contact with excipients. It is especially useful in early-phase development and for drugs with established bioequivalence pathways.
Conclusion
Direct compression remains a reliable and regulatory-friendly approach for the development of low-dose immediate-release tablets. By leveraging geometric scaling and robust excipient selection, formulators can efficiently develop cost-effective products with minimal development risks.
Read also:
- Selection of Suitable Process for Oral Solid Dosage Form
- Pharmaceutical Product Development Challenges
