Loss On drying Test (LOD Test) of Pharmaceuticals: Why, How and At what level

The Loss on Drying Test, or LOD test in pharmaceuticals, is a fundamental quality control procedure used to measure the amount of volatile matter (mainly water) in a sample.The following is a complete breakdown of why, how, and at what level this test is conducted:

Requirement details:

• Common Instruments: Oven dryer, Infrared/Halogen moisture balance
• Common methods: Oven drying, Infrared/Halogen drying
• Typical Temperature: 105°C (unless otherwise specified)

1. Why Perform a Loss on Drying Test?

• Moisture Control: Moisture can affect a drug’s stability, solubility, compressibility, flowability, and shelf life.
• Ensure Product Quality: Too much moisture may lead to hydrolysis, microbial growth, or poor tablet formation.
• Regulatory Requirement: Pharmacopoeias (e.g., USP, EP, JP) require it for raw materials, APIs, and finished products.
• Manufacturing Relevance: Ensures materials meet specifications for further processing (e.g., granulation, tabletting).

2. How Is Loss on Drying Performed?

a. Gravimetric Method

1. Weigh a sample of the substance (accurately measured).
2. Dry it in an oven at a specified temperature (e.g., 105°C, or per monograph) for a set time or until constant weight.
3. Cool in a desiccator and reweigh.
4. Calculate percentage weight loss by the following formula:

b. Infrared Drying (Halogen Moisture Analyser)

• Rapid drying using IR or halogen heating.
• Built-in balance continuously monitors weight.
• Suitable for in-process testing.

c. Karl Fischer Titration

• For accurate water content measurement, especially when only water (not other volatiles) needs to be measured.
• Preferred for heat-sensitive or low-moisture products.

3. At What Level Is LOD Acceptable?

• Specification depends on the different factors such as route of synthesis, characteristics of pharmaceuticals and regulatory limits.

Case Study/ example

• Microcrystalline cellulose: ≤ 7.0%
• Paracetamol: ≤ 0.5%
• Limits are stated in pharmacopoeial monographs (USP, Ph. Eur., etc.).

Conclusion

The Loss on Drying (LOD) test is a critical quality control measure in pharmaceutical manufacturing, used to determine the amount of moisture and volatile matter in drug substances, excipients, and finished products. Accurate LOD testing ensures product stability, efficacy, manufacturability, and compliance with regulatory standards. The method selected—whether gravimetric oven drying, infrared drying, or Karl Fischer titration—depends on the nature of the material and the required sensitivity. Acceptable moisture limits vary by substance and are defined in pharmacopoeial monographs. Maintaining LOD within specified limits is essential for ensuring the quality, safety, and shelf life of pharmaceutical products.

Related:

• How To Control Impurities In Pharmaceuticals: Get Mastery In …
• What is the Analytical Method Validation?
• The 7 Key Differences Between Validation and Verification

FQAs on LOD

Reference: USP<731>