Direct compression is NOT suitable for which type of drug?

• A. Low-dose drugs (e.g., lorazepam 1-5 mg)
• B. High-dose, high-solubility drugs
• C. Drugs with good flow properties
• D. Very large tablets

Answer: (A)

Direct compression relies on a powder blend that flows well and can be compacted to give each tablet an accurate, uniform amount of drug. When the drug dose is very small, the actual amount of API per tablet becomes a tiny fraction of the tablet weight, so even small variations in mixing, blending efficiency, or flow translate into relatively large deviations from the intended dose. That makes achieving strict content uniformity difficult with direct compression, which is why low-dose drugs are not well suited to this method. For higher-dose drugs, or those with good flow and high solubility, the amount of API per tablet is enough to average out mixing variations, and direct compression works more reliably. Very large tablets can be mechanically challenging, but the core limitation for direct compression is the ability to maintain consistent drug content at low doses.