Friday, December 11, 2020

Potency or Assay calculation of API

 Potency 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%

our API is 97%.

How to make 97% to 100%?

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.

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

 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.

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,

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 can not 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


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


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13 comments:

  1. What would be the potency calculation for Ciprofloxaxin HCl.
    Bulk batch size 153.300 Kg.
    Tablet weight 730 mg
    Label claim 500 mg as Ciprofloxacin

    ReplyDelete
    Replies
    1. What is the weight of API in kg?

      Delete
    2. From label claim, it seems that your API is ciprofloxacin Hcl and label claim states that each tablet contains ciprofloxacin as HCl. So we will have to remove salt and find the factor for salt compensation as follow
      Molecular wt of ciprofloxacin Hcl÷molecular weight of ciprofloxacin
      Add values
      367.8/331.133=1.110
      So 1.110 is salt removal factor
      Multiply it with tablet potency
      500×1.110=555 mg
      Mean 555mg of ciprofloxacin hcl is equivalent to 555 mg of ciprofloxacin.
      210,000×555=116.55 kg
      So your API should be 116.55 kg if it's 100%.

      Delete
    3. *555mg of ciprofloxacin hcl is eq to 500mg of ciprofloxacin

      Delete
    4. Is there any additional water added with Ciprofloxacin HCl?

      Delete
    5. additional water for?
      you mean for kneading?

      Delete
    6. I mean as a compound. As monhohydrate or dihydrate?

      Delete
  2. Can you mention a reference for more information?, thanks.

    ReplyDelete
  3. Love it..the way its written..

    ReplyDelete
  4. Thanks... Very informative...

    I want to know about assay on as such basis, Assay on anhydrous basis ?

    when to use that means, criteria for usage in formulation?

    When to not calculate assay in formulation?

    ReplyDelete