# Product Reconciliation In Pharmaceutical Industries

Product reconciliation is a process that is used to calculate and monitor the line loss or yield of a product that is under manufacturing.

Calculation of yield or line loss is monitored during every stage of manufacturing to ensure that yield or line loss is within the recommended range. All pharmaceutical industries have an SOP that defines the final yield of a pharmaceutical product after packaging.

What is the yield?

Yield is usually measured in percentage and it is the ratio of product quantity before manufacturing and product quantity after manufacturing or ratio of the theoreticalÂ  quantity of the product to the practical quantity of the product and its formula is as follow,

Â Â Â Â Â Â Â Â Â Â Â Â Yield =Quantity of product after manufacturingÃ·Quantity of the product before manufacturingÃ—100

orÂ

Â Yield =Actual Quantity Ã· Theoretical Quantity Ã—100

Example

In the pharmaceutical industry, a batch of tablets was manufactured having 50 kg standard batch size after dispensing and 49.0 kg after coating.

Calculate the yield of the product.

By using above formula add values in it as follow

Â Â Â Â Â Â Â Â Â Â Â Â yield=49Ã·50.0Ã—100=98.0%

So yield of the product is 98.0%.

What is line loss?

Line Loss is the measure of material loss during each manufacturing stage. Line loss may occur starting from dispensing stage to the end of finish product dispatch.

Line loss is measured by the following formula,

Line loss = Quantity of product before manufacturing – Quantity of product after manufacturing

Example

In the pharmaceutical industry, a batch of tablets was manufactured having 60 kg standard batch size after dispensing and 59.5 kg after coating.

Calculate the line loss of product.

By using above formula add values in it as

Â Â Â Â Â Â Â Â Â Â Â Â Line Loss=60-59.5=0.500 kg

Line loss of the product is 0.500 kg.

Reasons for Line loss

Line loss may occur due to the following reasons and in following stages.

Dispensing

• During dispensing some powder materials may swipe with return air due to the dusty environment.
• Some materials may adhere to the scopes during dispensing.
• Some materials mayÂ  adhere to the polythene bags.
• By any leakage or spillage.

Dispensing is a common procedure before starting of all dosage forms but manufacturing stages vary depending upon the type of dosage form here we will take the example of tablet dosage form to discuss yield and line loss.

Granulation

During granulation, line loss may occur due to the following main reasons

• Some materials may adhere to the polythene bags when they are removed from polythene bags.
• Material loss During sieving due to the dusty environment.
• During mixing and kneading some material sticks to the walls and blades of the mixer.
• Fine powder loss through dryer filters during the drying process.

During granulation, yield or line loss is calculated after drying and final blending stage.

Example

Â A tabler batch was dispensed having total standard weight as 75 kg. It was manufactured by a wet granulation method and dried in FBD. After drying, the product weight is 74.0 kg. Tablet weight is 750 mg and the number of tablets is 100,000 tablets.Calculate the yield and line loss of product.

First,we will calculate the yield of the product by the following formula,

Â Â Yield =Quantity of product after dryingÃ·Quantity of the product before manufacturingÃ—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Yield=74Ã·75Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â =98.66%

Now calculate the line loss by the following formula

Line loss = Quantity of product before Drying – Quantity of product after After drying

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Line loss= 75-74= 1 kg

After blending yield and line loss is calculated in the same way as mentioned above.

Example

The product discussed in the above example was sieved through an oscillating granulator and mixed in the blender. After blending its final weight is 73.7 kg. Calculate yield and line loss of the product.

First we will calculate yield of the product

Â Â Â Â Â Â Â Â Â %Yield=73.7Ã·75Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â =98.26%

Line loss isÂ

Â Â Â Â Â Â Â Â Â Â Â Â Line loss = 75-73.7=1.3 kg

Results

After drying yield is 98.66 and line loss is 1.0 kg.After final blending, the product yield and line loss is calculated for all granulation stages starting from sieving to the final blending,so total yield and line loss after completeÂ  granulation is 98.26% and 1.3 kg respectively.

Compression

During compression line loss may occur due to the following main reasons,

• Due to the dusty environment.
• Product loss during inprocess parameters checking.
• At the end of the compression stage, some powders or granules are left in the feeder or die and are not able to be compressed due to very low quantity.
• Some powders or granules may be left in tablet deduster.

Example

The above mentioned granulated product 73.7 kg was delivered to the compression area and after compression, the batch weight is 73 kg.Calculate yield and line loss of product at compression stage.

Use following formula

Â Â Â Yield =Quantity of product after CompressionÃ·Quantity of the product before compressionÃ—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Yield=73Ã·73.7Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â =99.05%

Line loss is calculated as

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Line loss = 73.7-73.0=0.7 kg

Results.

During compression stage yield is 99.05% and line loss is 0.7 kg.

If we want to calculate total yield and line loss of two stages mean granulation stage and compression stage then it is calculated as follow,

Â Yield =Quantity of product after CompressionÃ·Quantity of the product before granulationÃ—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Yield=73.0Ã·75Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â =97.33%

Line loss is calculated as

Line loss = Quantity of product before granulation – Quantity of product After compression

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 75-73=2.0 kg

So line loss of two stages is 2.0 kg and yield is 97.33%.

Coating

In tablet coating, extra weight is deposited on each tablet by spraying solution or suspension of the polymer so the weightÂ  of the product is increased.

Line loss in the coating may occur due to the following reason

• Wastage of coating material through the exhaust.
• Higher inlet temperature and low spray rate results in material loss.

Example

The coatingting material used to coat the above mentioned tablets batch is 2 kg. The batch size was 100,000 and we delivered 73 kg for coating. Number of tablets for 73 kg is

Â Â Â Â Â Â Â 73Ã—1000Ã—1000Ã·750=97333 tabs.

Coating material for each tablet isÂ

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 2Ã—1000Ã—1000= 20 mgÂ

so after coating, theoretically,each tablet weight should be

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â  750+20= 770 mgÂ

But After coating, we achieve 764 mg per tablet, meaning 6 mg loss per tablet.

Yield calculation for 100,000 tablets

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 100,000Ã—770= 77 kg

we have total weight of the batch after coating as follow

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 74.362 kg

Â Â Â Â Â Â Â Â Yield =74.362Ã·77Ã—100=96.574

Â Â Â Â Â Â Â Â Line loss = 77-74.362=2.638 kg

Results

We can see that as the number of stages of a manufacturing process increase, the yield is decreased and line loss is increased.

From granulation to coating total yield is 96.574 and line loss is 2.638 kg.

Product reconciliation for Encapsulation.

Hard gelatin capsules are used to fill powders, granules or pellets. Some powders are available which are ready to fill and some are mixed in a blender before filling in hard gelatin shells.

Example

In the pharmaceutical industry, a batch of 1000,000 capsules was filled with filling weight 150Â  mg and empty hardÂ  gelatin shell weight was 70 mg. After filling the total weight obtained is 219 kg.

Â Calculate yield and line loss.

First we will calculate the yield as follow,

Â Â Â Â Â Â Â Â Â Â Yield =Actual Quantity of CapsulesÃ·Theoretical Quantity of Capsules Ã—100

Actual quantity is 219 kg.

For theoretical quantity first we will calculate the weight of 1000,000 capsules.Â  For this multiply the total number of capsules by filled weight.

How to calculate filled weight?

Filled weight is the combination of filling weight and weight of an empty hard gelatin shell.

So Filled weight is

Filling weight + weight of empty shell

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 150+70=220 mg

So the filled weight is 220 mg.

Now calculate weight of 1000,0000 capsules as follow,

Â Â Â Â Â Â Â Â Â Â Â 1000,000Ã—220=22000,0000 mg

Convert milligrams intoÂ  kilograms as follow

Â Â Â Â Â Â Â Â Â 22000,0000Ã·1000Ã·1000=220 kg

So for yield use following formula

Â Â Â Â Â Â Â Â Â Â Â Â Â Yield =Actual Quantity of CapsulesÃ·Theoretical Quantity of Capsules Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Yield=221Ã·222Ã—100

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â =99.54%

Line loss is calculated as follow

Line loss =Theoretical or standardÂ  Quantity of capsules – Actual Quantity of capsulesÂ

Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â 222-221=1.0 kg

Results

After filling, the yield is 99.54% and line loss is 1.0 kg.

Conclusion

Product reconciliation is an important and critical process performed in the pharmaceutical industries.

During all manufacturing stages monitoring of yield or line loss gives us data to check the process efficiency and measures are taken to reduce the line loss and to increase the yield.

Popular Posts