Loss on Drying (LOD) can define as the amount of volatile matter of any kind that is driven off under the specified conditions. Loss on drying is determined by heating the sample below its melting point in an oven and it includes all volatile matter including water content and solvents.

Unless otherwise directed in the individual monograph, conduct the determination of Loss on Drying on a 1.0 to 2.0 g test specimen. The substance to be tested and, if it is in the form of large particles, reduce the particle size to about 2 mm by crushing before weighing it out.

The temperature specified in the monograph is to be regarded as being within the range of ±2°C of the stated value. Where capsules are to be tested, use a representative sample mixture, excluding the capsule shell, and it’s not fewer than 4 capsules. Where tablets are to be tested, use a representative sample mixture from NLT 4 crushed tablets.

Drying process should be continued until the results of two consecutive weighing do not differ by more than 0.5 mg/g. As a starting point, the recommended default value is automatic shut off value – 1 mg / 60 seconds (A60).

Loss on Drying is important in cases where the new drug substance is known to be hygroscopic or degraded by moisture.High moisture lead to sticking, picking, inappropriate flow of blend. Low moisture lead to low hardness, friability, capping and lamination.

LOD vs Water Content

The Loss on Drying test is designed to measure the amount of water & volatile matters in a sample when the sample is dried under specified condn’s (e.g. 105°C, 3hrs.). Loss on drying is calculated by heating the given sample below its melting pt. in an oven. Water content is also called as moisture content. It consists of only water, do not contain other volatile matter.Water content is determined by the Karl Fisher titration method.


  • USP-NF {731}
  • ICH Q6A