Over Drying vs Under Drying in Pharmaceutical Granules is an important topic because the moisture level of granules can affect drying performance, compression behavior, and overall tablet quality.

After wet granulation, the material contains a significant amount of moisture from the granulating solution. This moisture must be removed before the granules can move to the next stage, such as sizing, lubrication, and tablet compression.

But drying is not simply a matter of making the granules “as dry as possible.”

The target is to achieve the required granule moisture content within the approved process range.

If too much moisture remains, the granules may become underdried. If excessive moisture is removed, the material may become overdried.

Both conditions can create manufacturing problems.

This article explains the difference between over-drying and under-drying, their causes, effects on granules and tablets, LOD control, FBD drying parameters, and practical troubleshooting.

What Is Drying in Pharmaceutical Granulation?

In wet granulation, powder particles are converted into granules by adding a granulating liquid, often containing a binder.

The basic process is:

Dry mixing → Binder/granulating liquid addition → Wet massing → Wet screening → Drying → Sizing → Lubrication → Compression

After wet granulation, the wet granules contain residual liquid.

Drying removes the required amount of volatile material so that the granules reach the desired moisture level.

A Fluid Bed Dryer (FBD) is commonly used for this purpose because warm air passes through the wet granules and promotes evaporation.

The objective is not maximum drying.

The objective is controlled drying to the product-specific endpoint.

This distinction is important.

What Is Granule Moisture Content?

Granule moisture content refers to the amount of moisture remaining in the granules after the drying operation.

It can influence important properties such as:

Granule strength
Flow
Compressibility
Tablet hardness
Tablet tensile strength
Disintegration
Dissolution
Stability
Lubrication and compression behavior

Research has demonstrated that residual moisture after drying can have a significant effect on tablet crushing strength and other granule and tablet quality attributes.

Therefore, moisture is not simply something that needs to be removed. It is a critical process attribute that needs to be controlled.

What Is Under Drying in Pharma?

Under drying in pharma means that the granules have not been dried sufficiently to reach the approved moisture or LOD requirement.

In simple words:

Under dried granules contain more residual moisture than allowed or targeted for that product.

For example, suppose a product has an approved drying endpoint based on a specific LOD range. If the batch is discharged from the FBD before reaching that endpoint, the granules may remain too wet.

Common signs of under-dried granules

Depending on the formulation, you may observe:

Higher-than-target LOD
Granules feeling damp or soft
Increased tendency to agglomerate
Poor flow
Granules sticking together
Difficulty during sizing
Sticking or picking during compression
Variation in tablet weight or hardness
Changes in disintegration or dissolution

These are not automatic consequences for every formulation. The actual impact depends on the formulation, moisture sensitivity, granule structure, and validated process.

Causes of Under Drying

Several factors can result in insufficient drying.

1. Insufficient Drying Time

The most obvious cause is inadequate drying time.

If the batch is removed from the FBD before the required endpoint is reached, residual moisture may remain high.

Example

An operator notices that the granules appear dry and stops the process before the approved endpoint check is completed.

The material may look acceptable but still contain excess internal moisture.

This is why visual appearance alone should not be treated as the drying endpoint.

2. Low Inlet Air Temperature

If the inlet air temperature is lower than the established process range, evaporation may occur more slowly.

However, increasing temperature blindly is not the correct solution.

The appropriate temperature range should be established and controlled during process development and validation.

3. Low Airflow

FBD operation depends on proper air movement through the product.

If airflow is insufficient, fluidization and heat/mass transfer can be affected.

Possible reasons include:

Incorrect airflow setting
Filter loading
Equipment condition
Incorrect product load
Improper operating setup

4. Excessive Batch Load

A batch loaded beyond the validated operating range may not dry in the same way as a properly loaded batch.

The bed may not fluidize uniformly, and drying may become slower or less uniform.

5. High Initial Moisture

If too much granulating liquid was used during wet granulation, the starting moisture burden is higher.

The drying step then has more moisture to remove.

This is why granulation and drying cannot always be treated as completely separate operations.

6. Poor Fluidization

Uniform fluidization is important for consistent drying.

If the granules are not moving properly, some portions of the batch may dry faster than others.

This can create moisture variation within the batch.

7. Equipment or Filter Problems

A loaded filter, abnormal airflow, a malfunctioning temperature sensor, or other equipment issue can influence the drying process.

For this reason, equipment status and alarms should be reviewed whenever drying performance changes unexpectedly.

Effects of Under Drying

The effects of under drying depend heavily on the formulation.

1. Higher Residual Moisture

The most direct effect is moisture remaining above the approved target.

LOD or another approved moisture test may indicate this condition.

2. Poor Flow

Moist granules can become more cohesive and may not flow as freely.

This can affect:

Transfer
Sizing
Lubrication
Hopper movement
Die filling

3. Compression Problems

Excess moisture can change the behavior of the granules during compression.

Possible problems include:

Sticking
Picking
Variable hardness
Compression instability
Poor tablet appearance

The exact behavior depends on the formulation.

4. Changes in Tablet Quality

Granule moisture can influence tablet properties.

Studies have shown relationships between residual moisture after granule drying and tablet crushing strength.

Therefore, a drying problem can sometimes appear later as a compression or tablet-quality problem.

5. Stability Concerns

For moisture-sensitive products, excessive residual moisture can potentially affect chemical or physical stability.

The risk is product-specific and should be evaluated through formulation and stability studies.

What Is Over Drying in Pharma?

Over drying in pharma means removing more moisture than the formulation/process is designed to tolerate or going beyond the established drying endpoint.

In simple words:

Over dried granules have been dried excessively and may contain moisture below the desired process range.

This does not mean that every low LOD result automatically represents a product defect.

The important question is whether the measured result is outside the approved specification or validated process range and whether the lower moisture level affects product quality.

Causes of Over Drying

1. Excessive Drying Time

Leaving the batch in the dryer longer than required can remove additional moisture.

For example, if the endpoint has already been reached but drying continues because the operator waits for a fixed time instead of following the established endpoint procedure, over drying can occur.

2. Excessive Temperature

Higher temperature can increase the drying rate.

However, excessive heat may create additional risks, particularly for heat-sensitive materials.

Potential concerns include:

API degradation
Excipient changes
Physical changes to granules
Unwanted solid-state changes

The actual risk must be evaluated for the particular formulation.

3. Excessive Airflow

Higher airflow can increase drying efficiency depending on the equipment and operating conditions.

But “more airflow” does not automatically mean “better drying.”

The process should remain within the validated operating range.

4. Incorrect Endpoint Control

One common practical mistake is treating drying time as the endpoint.

For example:

“The batch normally takes 35 minutes, so we always run it for 35 minutes.”

That may not be scientifically sound if the process endpoint is actually controlled by moisture/LOD or another validated indicator.

Batch behavior can change because of:

Starting moisture
Batch size
Granule size
Product load
Ambient conditions
Equipment performance
Formulation characteristics

5. Incorrect Moisture Sampling or Testing

A poor sample can give a misleading picture of batch moisture.

Sampling should follow the approved procedure.

If the batch has moisture variation and only one non-representative sample is tested, the result may not represent the entire batch.

Effects of Over Drying

1. Excessively Low Moisture

The most obvious effect is moisture falling below the product’s desired range.

This can change granule behavior.

2. Changes in Compression Behavior

Moisture can influence how particles deform and bond during compression.

Therefore, changing the granule moisture level can affect:

Tablet hardness
Tensile strength
Friability
Compression behavior
Disintegration

Published research has demonstrated that dried-granule moisture can influence tablet crushing strength.

3. Possible Changes in Dissolution

Moisture and the drying history of granules can influence the physical properties of the granules and subsequently the finished dosage form.

However, it would be incorrect to say that over-drying always causes slow dissolution.

The effect depends on:

API properties
Excipient selection
Granule structure
Binder system
Compression conditions
Product formulation

Therefore, dissolution impact should be demonstrated through product-specific development and validation studies.

4. Changes in Granule Strength and Porosity

Drying can alter granule structure.

Research into pharmaceutical fluid-bed drying emphasizes the importance of understanding moisture distribution and granule properties because these can affect downstream tabletability and product quality.

5. Possible Electrostatic or Handling Issues

Very dry powders can sometimes show increased static-related handling problems.

Again, this is formulation and environment dependent.

Over Drying vs Under Drying: Main Difference

The easiest way to understand the difference is:

Parameter	Under Drying	Over Drying
Moisture	Too high	Too low
Main issue	Insufficient moisture removal	Excessive moisture removal
LOD	Above approved target/range	Below approved target/range
Granule condition	May remain damp	May become excessively dry
Common cause	Insufficient drying	Excessive drying
FBD time	Too short	Too long
Temperature	May be too low	May be too high
Flow	May be affected	May be affected
Compression	Can cause problems	Can cause problems
Tablet quality	May be affected	May be affected
Corrective approach	Investigate and control drying	Investigate and prevent excessive drying

Important: The acceptable moisture/LOD range is product-specific. There is no single LOD value that is correct for every pharmaceutical granule.

What Is LOD of Granules?

LOD means Loss on Drying.

USP General Chapter <731> describes Loss on Drying as the amount of volatile matter driven off under specified test conditions.

In pharmaceutical manufacturing, LOD may be used to assess the moisture/volatile content of a material.

However, LOD is not automatically identical to pure water content.

That distinction matters.

If water is the only volatile component, LOD may be a useful measure of moisture. But if other volatile substances are present, LOD can include their loss as well. USP notes that when water is the only volatile constituent, a water determination procedure may be appropriate.

Therefore, always follow the product’s approved analytical method and specification.

LOD in Wet Granulation

During wet granulation, LOD can be used as one of the controls for determining whether the dried granules have reached the required condition.

A simplified process is:

Wet granules → FBD drying → Sample collection → LOD/moisture testing → Compare with approved requirement → Release for next step

The actual sampling frequency, test method, acceptance range, and endpoint procedure must come from the approved batch manufacturing record, SOP, specification, and validated process.

What Is the Drying Endpoint?

The FBD drying endpoint is the point at which the granules have reached the established moisture condition required for the product.

It should not simply mean:

“The granules look dry.”

A properly established endpoint may involve:

Product temperature
Exhaust temperature
Drying time
Moisture/LOD
Equipment parameters
In-process testing
PAT/NIR, where applicable

Modern pharmaceutical development increasingly uses process monitoring tools to understand granule moisture during FBD operation. A 2026 study evaluated NIR and Raman spectroscopy for monitoring granule moisture and determining the drying endpoint during commercial-scale FBD processing.

FBD Drying Process: What Should Be Controlled?

During the fluid bed dryer granules process, several parameters may be important.

1. Inlet Temperature

Controls the temperature of the incoming drying air.

It should remain within the established process range.

2. Airflow

Adequate airflow is required for proper fluidization and drying.

3. Product Temperature

Product temperature provides useful information about the drying state and should be monitored according to the validated process.

4. Drying Time

Time is an important process parameter but should not automatically be treated as the only endpoint.

5. Batch Load

The quantity of material loaded into the FBD should remain within the validated range.

6. Filter Condition

Filter performance can influence airflow and drying behavior.

7. Moisture/LOD

The final moisture condition should be confirmed using the approved test or validated endpoint strategy.

FBD Moisture Control: Practical Approach

A practical control strategy can be thought of as:

Start with controlled wet granules

↓

Load FBD within approved range

↓

Set validated drying parameters

↓

Monitor temperature and airflow

↓

Observe drying behavior

↓

Perform approved endpoint check

↓

Confirm moisture/LOD

↓

Stop drying at the established endpoint

↓

Unload and transfer under controlled conditions

This approach is much safer than simply saying:

“Dry for 30 minutes.”

The actual drying time can vary between batches, while the required product condition remains the key objective.

How to Check Moisture Content of Granules

The method depends on the product and approved specification.

Common approaches can include:

LOD Testing

A sample is tested according to the approved LOD method.

Moisture-Specific Methods

Where appropriate, a validated water-specific method may be used.

NIR/PAT

Near-infrared methods can provide rapid moisture monitoring when properly developed, calibrated, validated, and implemented.

Research has demonstrated the use of NIR and Raman techniques for monitoring granule moisture during fluid-bed drying.

Important GMP Point

The analytical method and sampling procedure must be approved and validated as applicable.

Do not replace an approved QC method with an informal moisture check simply because it is faster.

Why You Should Not Use One Universal LOD Acceptance Criteria

This is one of the most important points for production and QA personnel.

You may see different moisture values used for different formulations.

There is no scientifically correct statement such as:

“All pharmaceutical granules should have 1–3% LOD.”

That would be misleading.

The appropriate LOD acceptance criteria depend on the formulation and manufacturing process.

Factors can include:

API properties
Excipient properties
Binder type
Granulation liquid
Granule size
Compression behavior
Stability
Dissolution requirements
Product development data
Process validation data

The approved product specification and validated process should therefore determine the required range.

Real Manufacturing Example: Under Drying

Imagine a wet granulation batch has completed the FBD cycle.

The operator checks the granules, and they appear acceptable.

The material is transferred for sizing.

During the next operation, the granules show increased sticking and poor flow.

QC testing later indicates that the moisture level is above the approved requirement.

What should be investigated?

QA/production should not immediately blame the FBD operator.

The investigation should consider:

Actual batch size
Quantity of granulating liquid
Wet massing time
FBD loading
Inlet temperature
Airflow
Drying time
Product temperature
Filter condition
Sampling method
LOD testing
Previous batch trend
Equipment performance

This is a much stronger GMP approach because it looks for the root cause rather than simply assigning blame.

Real Manufacturing Example: Over Drying

Consider another batch.

The product normally reaches its drying endpoint within the validated operating window.

However, the operator continues drying because the batch was assumed to require additional time.

The moisture result is significantly lower than the established target.

The batch then shows a different compression behavior from previous successful batches.

What should be checked?

The investigation may include:

Drying time
Inlet temperature trend
Airflow trend
Product temperature
Endpoint determination
Operator entries
Equipment alarms
Calibration status
LOD result
Sampling procedure
Comparison with previous batches

Again, the purpose is to determine why the process moved outside its expected condition.

What If LOD Is Out of Limit?

If the LOD result is outside the approved acceptance criteria, the batch should not simply be released or re-dried based on an informal decision.

The batch should be handled according to the site’s approved procedures.

Depending on the situation, this may involve:

Informing the responsible production/QA/QC personnel.
Placing the material or batch under the appropriate status.
Verifying the test result and laboratory procedure as required.
Reviewing sampling adequacy.
Checking equipment and process records.
Initiating a deviation or investigation when required.
Performing root-cause analysis.
Assessing product impact.
Determining whether any additional processing is scientifically justified and authorized.
Documenting the final decision.

GMP principles emphasize defined processes, documented controls, investigation of quality issues, and appropriate quality oversight.

Never assume that “drying again will fix it.”

Additional drying is a process decision that must be supported by the approved procedure, product/process knowledge, and QA authorization where applicable.

How to Prevent Over Drying and Under Drying

A strong preventive system should include the following controls.

1. Define the Drying Endpoint

The product should have a scientifically justified drying endpoint.

2. Follow Validated Parameters

Control parameters such as:

Inlet temperature
Airflow
Product temperature
Drying time
Batch load

within their approved ranges.

3. Use Proper Sampling

The sample should represent the batch.

4. Trend LOD Results

Do not look only at pass/fail results.

Trending can identify gradual process changes.

For example:

2.1% → 2.3% → 2.6% → 2.9% → 3.2%

Even before a specification failure occurs, such a trend may deserve attention if it differs from normal process behavior.

5. Maintain FBD Equipment

Regularly check:

Filters
Airflow system
Temperature sensors
Product temperature probes
Gaskets
Air handling components
Calibration status

6. Train Operators

Operators should understand that:

Drying is controlled by the established process endpoint, not simply by appearance.

7. Follow the BMR/SOP

The operator should record actual process parameters rather than relying on memory.

8. Investigate Deviations Properly

A failed LOD should trigger an appropriate investigation rather than an immediate assumption about the cause.

Moisture Effect on Tablet Hardness

Moisture can affect particle-particle bonding during compression.

This means that changes in granule moisture can influence tablet mechanical properties.

Research on wet-granulated pharmaceutical material found that residual moisture after drying had a significant effect on tablet crushing strength.

Therefore, if a batch suddenly shows abnormal tablet hardness, granule moisture should be considered as one possible contributing factor, along with compression force, granule size distribution, lubricant level, compression speed, tooling, and other process variables.

Moisture Effect on Dissolution

It is tempting to say:

“More moisture means slower dissolution.”

That is too simplistic.

The relationship between moisture and dissolution is formulation-dependent.

Changes in drying can alter granule structure, porosity, particle bonding, and subsequent tablet properties. These changes may affect drug release.

Therefore, any claimed relationship between drying condition and dissolution should be supported by product-specific development or validation data.

This is one reason why pharmaceutical process development looks at the relationship between process parameters and critical quality attributes rather than controlling each manufacturing step in isolation.

Moisture Effect on Compression

During compression, granules must deform and bond in a predictable manner.

If their moisture condition changes significantly from the established process state, the compression behavior may also change.

Possible observations include:

Hardness variation
Friability changes
Sticking
Picking
Capping
Lamination
Weight variation
Changes in disintegration

But these defects have many possible causes.

For example, capping should not automatically be blamed on over drying.

A proper investigation should consider the complete compression process.

Drying Effect on Tablet Quality

The drying step can influence tablet quality indirectly because it changes the physical condition of the granules used for compression.

The relationship can be represented as:

Wet Granulation

↓

Drying

↓

Granule Moisture

↓

Granule Properties

↓

Compression Behavior

↓

Tablet Quality

This is why drying should be treated as an important part of the overall manufacturing process rather than as a simple moisture-removal step.

Difference Between Moisture Content and LOD

These terms are often used interchangeably in manufacturing conversations, but technically they are not always identical.

Moisture Content

Usually refers specifically to the amount of water present.

LOD

Measures the loss in weight under specified drying conditions and may include volatile substances other than water.

USP <731> specifically defines the LOD procedure around volatile matter lost under specified conditions.

Therefore:

LOD should not automatically be interpreted as pure water content unless the method and material justify that interpretation.

This distinction is useful when writing investigations, specifications, and technical reports.

Common Mistakes During Granule Drying

Mistake 1: Drying only by fixed time

A fixed time can be part of the process, but it should not replace an established endpoint strategy.

Mistake 2: Judging dryness by appearance

Granules can appear dry while still having unacceptable internal moisture.

Mistake 3: Increasing temperature without authorization

Higher temperature is not always the answer to slow drying.

Mistake 4: Ignoring batch load

A different product load can change drying behavior.

Mistake 5: Ignoring airflow

Poor fluidization can create drying variation.

Mistake 6: Taking a poor sample

An unrepresentative sample can lead to an unreliable conclusion.

Mistake 7: Using one LOD limit for every product

Different formulations can have different moisture requirements.

Mistake 8: Re-drying without investigation

Additional drying should be handled according to approved procedures and quality requirements.

Mistake 9: Blaming the operator immediately

The root cause may be equipment, formulation, sampling, process parameters, or environmental conditions.

Troubleshooting Guide

Observation	Possible Cause	What to Check
High LOD	Insufficient drying	Drying time, temperature, airflow
Low LOD	Excessive drying	Drying time and temperature trend
Slow drying	Poor airflow	Airflow, filter, fluidization
Uneven moisture	Poor fluidization	Bed behavior and loading
Damp granules	High starting moisture	Granulation process
Compression sticking	Excess moisture or other causes	Moisture, lubricant, compression conditions
Hardness variation	Moisture variation or other process variables	LOD trend, granule size, compression
Unexpected dissolution change	Granule/tablet property change	Drying, granulation, compression
Batch-to-batch drying variation	Process/equipment variation	Parameter trends and equipment condition

GMP Documentation for Granule Drying

A well-controlled drying operation should have appropriate documentation.

Depending on the site’s system, records may include:

Product and batch number
Equipment identification
Batch quantity
FBD parameters
Inlet temperature
Outlet/product temperature
Airflow
Drying time
Endpoint determination
LOD/moisture result
Sampling details
Operator signature/initials
Checker verification
Equipment status
Deviations, if applicable

The objective is traceability.

A reviewer should be able to understand what happened during the drying operation by looking at the manufacturing records.

This is consistent with the broader GMP principle that pharmaceutical processes should be clearly defined, controlled, documented, and appropriately validated.

FAQ

What is over drying in pharmaceutical granules?

Over drying means removing excessive moisture from granules so that their moisture level falls below the desired or approved process range.

What is under drying in pharmaceutical granules?

Under drying means the granules have not been dried sufficiently and retain more moisture than permitted or targeted for the product.

What is the difference between over drying and under drying?

Under drying means too much moisture remains, while over drying means too much moisture has been removed.

What causes under drying in FBD?

Common causes can include insufficient drying time, low temperature, inadequate airflow, excessive batch loading, poor fluidization, high starting moisture, or equipment-related problems.

What causes over drying?

Common causes include excessive drying time, excessive temperature, excessive airflow, or incorrect endpoint control.

What is LOD of granules?

LOD, or Loss on Drying, is a test that measures the loss of volatile matter from a sample under specified conditions. It is commonly used as a moisture-related test, but it is not necessarily identical to water content.

What is the acceptable LOD for pharmaceutical granules?

There is no universal LOD limit for all granules. The acceptance criterion should be based on the approved product specification and validated process.

Can over drying affect tablet hardness?

It can. Changes in residual granule moisture can influence compression and tablet mechanical properties. However, the actual effect is formulation-specific.

Can under drying cause sticking during compression?

It can contribute to sticking in some formulations, but sticking has several possible causes. Moisture should therefore be evaluated along with other compression variables.

How is the FBD drying endpoint determined?

The endpoint should be based on the validated process and may involve process parameters and/or an approved moisture or LOD measurement. Advanced manufacturing processes may also use PAT techniques such as NIR for moisture monitoring.

Is LOD the same as moisture content?

Not always. LOD measures loss of volatile matter under specified conditions, whereas moisture content specifically refers to water. The distinction depends on the material and analytical method.

Should all pharmaceutical granules be dried to the same moisture level?

No. The appropriate moisture range depends on the formulation, process, material properties, and product requirements.

Conclusion

The goal of pharmaceutical granule drying is not to make the granules as dry as possible.

The goal is to achieve the right moisture condition for that particular product and process.

Under-drying leaves excessive residual moisture.

Overdrying removes more moisture than the process requires.

Both conditions can influence granule behavior and may eventually affect tablet manufacturing and product quality.

The best control strategy is:

Controlled granulation → Controlled FBD parameters → Proper endpoint determination → Representative moisture/LOD testing → Documented results → Trend monitoring → QA oversight

Most importantly, do not use a universal LOD value or fixed drying time for every product. The correct endpoint should come from product and process knowledge, development studies, approved specifications, and the validated manufacturing process. FDA process-validation guidance emphasizes understanding and controlling manufacturing processes, while WHO GMP principles require pharmaceutical processes to be appropriately defined, controlled, documented, and validated.

Authoritative References

Saurabh Saini

Saurabh Saini is a pharmaceutical warehouse professional with over 3 years of hands-on experience in GMP-regulated manufacturing. He currently works as a Junior Officer – Warehouse at Abbott Healthcare and previously served as an Assistant Officer at Mankind Pharma. His expertise includes Raw Material Receipt, Raw Material Dispensing, Warehouse Operations, Inventory Management, GMP documentation, and SOP implementation. Through Pharma GMP Guide, he shares practical GMP knowledge, SOPs, regulatory guidance, and pharmaceutical best practices to help students and industry professionals.