API quantity during Bill of Material Calculations

Potency or Assay calculation of API

Potency calculation of Active pharmaceutical ingredients is the most common activity which is
performed on the daily basis by pharmacists in the pharmaceutical industry.it is a common
observation that the majority of pharmaceutical professionals don't know how to calculate the potency
or assay of an active pharmaceutical ingredient.

What is API
 API is the Active pharmaceutical ingredient which gives pharmacological or therapeutic
activity.
 Only API is the element in a complete dosage form which gives effect to cure, treat or prevent
disease.
 All other ingredients are called excipients which have no pharmacological effect.
 API is the pharmacological agent so its quantity should always be measured in a precise
manner.
 API is delivered according to the label claim.
 To calculate the potency of API following factors are considered.
 Moisture Content of API
 Salt removal or factor adjustment.

Moisture Content
Amount of moisture content in the API is checked in the certificate of Analysis of that specific API
and its adjustment is made to maintain its efficacy.

Salt removal or factor adjustment.

Some active pharmaceutical ingredients are used in salt form like Metformin Hcl and some are used
without salt like Sitagliptin Phosphate in which phosphate factor is removed from sitagliptin.

The question is how will we know that when to use API with salt and when to use API without
salt?
The answer to the question is that for this we have to check or read the label claim. If the label claims
that each tablet contains Sitagliptin phosphate then we do not need to remove the salt form and if the
label claim states that each tablet contains Sitagliptin "as phosphate" then we have to remove the salt
form from API.
Many active pharmaceutical ingredients give pharmacological effect with salt form and some API
give effect without salt. The attached salt is used just as a carrier to improve solubility or dissolution
etc.

Calculation For Moisture Content

Suppose we have an API whose potency or assay is 100% and CoA claims that it has 3% Moisture
content.
How will we adjust M.C Of the API?
Usually, We use 100% of API and in the above case, we have 100% of API and 3% moisture content
so, first of all, compensate moisture content as follow
Assay-MC÷100×100
Adding above values in the formula,
100-3÷100×100=97%
 API quantity during Bill of Material Calculations

Our API is 97%.

How to make 97% to 100%?

Example
In a pharmaceutical company,50 kg API is used to manufacture 100,000 tablets. Each tablet contains
500 mg API and an assay of API is 100%. The moisture content in API is 4%.
Calculate the MC compensation for the above statement.
Use above formula to calculate factor
100÷(Assay-Mc)
100÷(100-4)=1.04
Multiply this factor value to the amount of API in kilograms as follow,
50×1.04=52kg
or add 4% extra quantity of API to compensate MC as follow,
50×4/100= 2 kg

We have to add 3% extra API to compensate MC and make it 100% or use the following factor to
calculate API
100÷(Assay-Mc)
After adding values
100÷(100-3)=1.03
1.03 is the MC or moisture content compensation factor.

So
50+2=52 kg
Explanation
In simple words, 4% moisture content is present along with API in the above statement and according
to by weight calculations, if we weigh 50 kilograms of API then actually 4% of 50 kg is moisture
content which is 2 kg so we will add extra 2 kg to compensate moisture content and statement will be
as follow
 52 kg of API with 4% MC is equivalent to 50 kg of API without MC.

Effect of Moisture Content on Assay

If we calculate assay for above statement without moisture compensation and dispense API 50 kg
with 100% assay then assay for 50 kg with moisture content is as follow,
Assay of 50 kg is =100%
2 kg is the moisture content so actual API is
50-2=48kg
Assay of 48 kg is =100/50×48=96%

If we add moisture compensation before dispensing the API then we will dispense 4% more API and
the total quantity will be 52 kg.
So as we know,
Assay of 48 kg is =96%
Then
Assay of 52 kg is =96/48×52=104%
In 104%, 4% is the moisture compensation and 100 % is the assay.
 API quantity during Bill of Material Calculations

In term of individual tablets, if we take

50 kg and 100% assay then with no moisture content adjustment, each tablet will contain 500 mg API
and in each 500 mg tablet 4% is moisture content which is
500×4/100= 20 mg
Mean each tablet contains 20 mg less API so it's assay will also be lower than 100% as,

Assay of a tablet containing 500 mg API is= 100%

Our tablet contains 20 mg less API so
500 mg API – 20 mg API=480 mg API
so
Assay of a tablet containing 480 mg API is= 100÷500×480=96%
so we will add 4% extra API or multiply 500mg by above-mentioned factor 1.04 to compensate
moisture content.
500×1.04=520mg
so
Assay of a tablet containing 520 mg API is= 100÷500×520=104%
in 104, 4% is the moisture compensation and 100% is assayed.

Salt removal or Factor Adjustment

Salt removal means weather in our formulation pharmacological effect is produced by API with salt
or API without salt
e.g sitagliptin or sitagliptin phosphate.
For salt removal following formula is used

Molecular weight Of API with salt÷Molecular weight of API without Salt

Example
Label claim of a tablet states that each tablet contains Sitagliptin phosphate 50 mg.
then
In the pharmaceutical industry,10 kilograms of sitagliptin phosphate are used to manufacture 200,000
tablets. Strength of the tablet is 50 mg.
How much Sitagliptin phosphate is present in one tablet?
For this
First, of all, convert 10 Kilograms into milligrams
10×1000=10,000 grams
10,000×1000=10,000,000 milligrams

Divide it by batch size as follow, 10,000,000/200,000=50 mg

So each tablet contains 50 mg of sitagliptin phosphate.
Now let's take the above statement in another way as,
Label claim of a tablet states that each tablet contains Sitagliptin as phosphate 50 mg.
then look at another example
In a pharmaceutical industry 10 kg, Sitagliptin phosphate is used to manufacture 200,000 tablets.
Strength of tablet is 50 mg
How much Sitagliptin phosphate is present in one tablet?
First of all convert kilograms into milligrams as follow
10 ×1000 =10,000 grams
10,000×1000=10,000,000 milligrams
Divide it by batch size as follow,
 API quantity during Bill of Material Calculations

10,000,000/200,000=50 mg
So each tablet contains 50 mg of sitagliptin phosphate.
But according to the above statement, we need sitagliptin 50 mg, not sitagliptin phosphate so we will
remove phosphate. (Focus on the term "as phosphate")
How will we do that?
According to the above statement, the pharmacological effect is produced by sitagliptin, not by
sitagliptin phosphate.
So how will we remove phosphate attached with sitagliptin?
One explanation is that physically we cannot separate phosphate from sitagliptin so add compensation
factor like moisture content. So extra weight of API is added in the formulation.
Calculation
For salt removal or factor calculation, we use the following calculation,
The Molecular weight of sitagliptin with phosphate÷Molecular weight of sitagliptin
without phosphate
after adding values
505.31 g/mol÷407.31 g/mol
=1.24
1.24 the factor for salt removal or factor adjustment.
so
Multiply the factor with total API in kilograms or with the strength of individual tablet as follow,
10 kg × 1.24=12.4 kg
or
50 mg × 1.24 = 62 mg/tablet
From the above statement, it is clear that to remove phosphate from sitagliptin we have to use 12.4
kilograms of Sitagliptin phosphate instead of 10 kilograms of sitagliptin phosphate.
so
12.4×1000×1000÷200,000=62 mg
In label claim, it is written as
Each tablet contains 62 mg of sitagliptin phosphate equivalent to 50 mg of sitagliptin.
Mean 12 mg is the phosphate and 50 mg is the sitagliptin.
How to calculate the %age of API in a given formulation?
In the pharmaceutical industry, a Tablet product Z is manufactured which contains sitagliptin
phosphate and tablet strength is 25 mg. The manufacturing order of the product contains the following
ingredients.
Label claim states that
Each tablet contains sitagliptin as phosphate 25 mg.
Find the %age of active pharmaceutical ingredient in the given formulation.
Manufacturing Order
Product Name = Z 25 mg
Batch Number = Y
Batch Size = 200,000 Tablets
 API quantity during Bill of Material Calculations

Ingredient Unit Quantity

Sitagliptin Phosphate kg 6.324

Avicel PH 101 kg 11.276

PVP K 30 kg 0.800

Ac-di-sol kg 1.200

Aerosil kg 0.100

Mg Streate kg 0.300

Total weight is = 20 kg
Tablet weight is 100 mg
How to Find the %age of active pharmaceutical ingredient?
To find the %age of API in the above formulation following procedure is used.
 First of all convert kilograms of API into milligrams as follow
6.324×1000×1000=6324,000 mg
 Divide the number of milligrams by batch size as following
6.324×1000×1000=6324,000 mg÷200,000
= 31.62 mg
 Now divide it by tablet strength which is 25 mg in the above case so
31.62÷25=1.2648
 As we know from label claim that we have to remove salt so use the following formula

Molecular weight of sitagliptin with phosphate÷Molecular weight of sitagliptin without

phosphate
after adding values
505.31 g/mol÷407.31 g/mol
=1.24
 Now divide 1.2648 by 1.24 as
1.2648÷1.24=1.02
 For %age multiply 1.02 by 100 as
1.02×100=102%
Result
 In the above formulation API %age is 102%.

Conclusion
Active pharmaceutical ingredients in a pharmaceutical product are always used after proper
adjustments for moisture content and salt removal