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Pharmaceutical calculations

Quality Control

jehangir

Muhammad jehangir

Mar '17

What is reference of Pharmaceutical calculations.

1-Potency adjustment

2-LOD/Water adjustment

3- Batch calculation regarding quantity of API added in Master formula

created

Mar '17

last reply

Aug '21

replies

Mahmoud

Mahmoud Alabdullah

Mar '17

Think of these calculations in logical order:

Remove or account for the water

Solve for the API you have left in the remaining chemical

Decide if you need to correct for the salt in the chemical since the formula calls for the base

Remembering these three steps in this order will remind you that the salt base conversion is performed
with the

molecular weights (MW) of the chemical without the water.

Calculation 1: Water Correction

Water (or LOD) is usually expressed as a percentage on the CofA, such as 7% water. This means that

proportionally every 100 mg of the chemical actually has 7.0 mg of water.

The water correction factor to apply is [(100-Water%)/100] g/g chemical. Let’s apply this formula to a
theoretical

lidocaine HCl monohydrate lot we received where the CofA lists a water concentration of 7%. The water

correction factor would be: (100/(100-7.0)) = 1.075.

Even though you could get a pretty good estimate of the water correction factor by using the molecular
weight
(MW) for those APIs that are hydrated, there are always small differences between that theoretical
number and

an actual determination as reported in the CofA. Using the MW of lidocaine HCl monohydrate, the water
factor

formula would look like this (288.81/(288.81-18)) = 1.066 and result in a difference of 0.009

Since USP allows lidocaine HCl monohydrate to have between 5% and 7% water, the most accurate
correction

would therefore come from the CofA.

Calculation 2: Assay Correction

Calculate the amount of API in your chemical with the assay correction.

Most assays assigned in the CofA are

done after the water has been removed (on an anhydrous basis). In essence, the API is dried and then a
chemical

analysis is performed on the chemical to determine the amount of pure API that is in the particular lot.
Most

USP monographs only allow a very narrow band of acceptability, but there are cases where the
acceptable range

can be quite large, especially in biologics and antibiotics.

Most of the time, the assay information given on the CofA is listed as a percentage, therefore, making it
easier

to calculate. Sticking with the example chemical, lidocaine HCl monohydrate that we used above, let’s
say the

actual assay was 98.0% (which is within the USP monograph range o

f 97.5% to 102.5%); this means that the API

has only .98 gm of API per gm of chemical. The correction factor to apply on your compounded
preparation

should be (100/98.0) = 1.020.

Calculation 3: The Salt to Base Corrections

First determine what the prescription is requesting. Unfortunately, some prescribers do not take into
account the

subtle and not so subtle differences in casual name and exact name of an API. If ever in doubt, always
contact

the practitioner first and have the USP monograph on hand when discussing with them. As always make
sure

you are labeling the prescription correctly. For example, don’t label a prescription lidocaine 1% if you
made it

with 1% of the hydrochloride salt. Instead label it lidocaine HCl 1%.

Once you feel confident that the correct chemical is identified, the next step is to correct for the proper
weight of

the chemical. This conversion is obtained by the MWs of the base and salt form of the API. The ratio of
these two

MWs will provide the correction factor to apply.

Example using lidocaine HCl monohydrate: use the MW of the lidocaine (MW 234.32 g/mole) and the
lidocaine

HCl (MW 270.80 g/mole), not the hydrated lidocaine HCl monohydrate (MW 288.81 g/mole). So if you

have lidocaine HCl monohydrate and need the lidocaine base, the conversion formula for the salt to
base is

(270.80/234.32) = 1.156.

ow that you have these three calculations, all generated by your API’s CofA, you can continue on with

other calculations to further ensure the potency of your compounded preparation.

Chemical Weight = Remove Water, Correct for Assay and then Correct for Salt / Base (if needed).

Therefore: Chemical Weight = API Weight x Water Conversion x Assay Conversion x Salt Conversion (if

needed).

For the lidocaine HCl monohydrate to lidocaine base the result using the example above would be:

Weight Lidocaine HCl Monohydrate = Lidocaine API Weight Needed x 1.075 x 1.020 x 1.156 = Lidocaine

Weight Needed x 1.268

Using just the MW for the conversion would give us a theoretical result of:
Weight Lidocaine HCl Monohydrate = Lidocaine Weight Needed x (288.81/234.32) = Lidocaine Weight

Needed x 1.233

Just to further confuse matters, there are preparations that do not require a correction for the salt form
or water

content of the chemical. The most notable being morphine sulfate injection, which is made with
morphine

sulfate pentahydrate, and the potency of the injection is based on morphine sulfate pentahydrate. The
USP

monograph for morphine sulfate injection specifies that it should contain not less then 90% and not
more than

110% of morphine sulfate pentahydrate. So when compounding with this API you do not need to adjust
for the

water content or the salt form of the chemical. Always consult the USP for the applicable monograph.

Since all these corrections will most likely need to be done for the same preparation, the corrections can
be applied

in any order or in one step. However, in most cases you will need to take into account the chemical
assay and the

water, either absorbed or in the chemical formula, to get the correct amount of the API in your
preparation.

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karoderichard@gmail.com richard

Aug '21

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Potency adjustment

R&D

aisha

aisha qamar

Basic

Dec '20

Discussion about the topics related to pharmaceutical research and development (R&D).

How to adjust the potency of Tamsulosin HCl in BMR according to the assay report (99.74%).?

created

Dec '20

last reply

Jun '21

replies
sunilrbudhkar

Regular

Dec '20

Generally in Pharma R & D the quantity of drug (API) to be added in a batch is adjusted to 100% based
on its potency or % assay by applying correction factor as follows,

Correction factor = 100 / % Assay (potency) obtained as per Assay report

Quantity to be added in a batch = Theoritical quantity X Correction factor (as above)

Similarly we can calculate the quantity of drug (API) to be added in a batch on moisture free basis
(taking in to account actual moisture content obtained as per COA report of that drug (API). The
calculation is as follows,

Correction factor = 100 / (100 - % moisture content in the API)

Quantity to be added in a batch = Theoritical quantity X Correction factor (as above)

For example, For Amoxicillin trihydrate the actual quantity to be added in a batch is calculated based on
actual moisture content obtained in Amoxicillin trihydrate API.

aisha

aisha qamar

Basic

Dec '20
thankyou.

Is it compulsory to adjust potency to 100% when we are formulating extended release drug product?

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sunilrbudhkar

Regular

Dec '20

It is not mandetory to adjust potency / Assay to 100% when formulating any pharmaceutical product. In
any case it must comply finished product specification in which Assay is also included.

Generally, there is no need to adjust potency to 100% in the formulation, if assay limit of that API (Active
ingredient) is 98% or above (in tht raw material API). If assay limit of API (as a raw matewrial) is less than
98% or if there is moisture content (significant amount) then it is necessary to compensate for assay and
moisture content to 100% in the formulation. This is required to achieve assay value within limit as per
finished product specification as well as to be within limit up to shelf life (up to expiry date) of that
formulation.

There should be internal R & D policy or SOP to govern this aspect.

1
aisha

aisha qamar

Basic

Dec '20

thanks

sunilrbudhkar

Regular

Dec '20

You are always welcome.

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arreddy85

Raghavender Reddy Anthamgari

Jun '21

Hi
Is there any guideline reference to follow below statement

Calculate the quantity of API if assay is below 100% on as is basis. If the assay is 100% or above consider
the theoretical quantity.

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