[Lim]

Hi I would like to ask about one question on Secondary pharmaceutical production operations, here is the qns:

what is the purpose of ensuring a uniform mix of powders in the production of final dosage form?

From what I know in this questions, I am not sure if my answers are correct or wrong my answer is:

Uniform mix of powders in the production of final dosage form is important as non-uniform mixture of powders will affect the desired volume of powder required in encapsulations and tablet compression event. Which thus may affect a particular drug efficacy(e.g. non-uniform mixture drugs may cause more side effects than a uniform mixture drugs).

I would hope to just confirm whether my answers are correct. If there are any mistakes please do correct me.

[Borek]

If the mixture is not uniform, can you be sure about dosage per tablet?

[Arkcon]

Borek:'s answer is a better one than yours.

What you wrote:

Uniform mix of powders in the production of final dosage form is important as non-uniform mixture of powders will affect the desired volume of powder required in encapsulations and tablet compression event. Which thus may affect a particular drug efficacy(e.g. non-uniform mixture drugs may cause more side effects than a uniform mixture drugs).

Is somewhat accurate, but not really.  Yes, inhomogeneous mixing may affect the volume of the powder.  But highlighting side-effects from a poorly mixed formulation is a little far-fetched.  I have to wonder where you got a response so carefully worded, that really missed the point.  Maybe you're copying from a textbook or other source at random?   Don't do that.  In literature, that's encouraged, because its artistic, in science, its just bad.

[Lim]

yah this answers are from textbooks, anyway  if mixture not uniform I would say dosage per tablet will not be desired dosage that you want, with this can it be explain like this:

if dosage per tablet is not  acceptable(from what i think)  it will result in every drug products will also having large deviation of weight between each other. So since non-uniform mix of powder affects weight and volume in powder, we could said that purpose of uniform mixing is to get the desired concentration of the drug products

[Arkcon]

yah this answers are from textbooks, anyway  if mixture not uniform I would say dosage per tablet will not be desired dosage that you want,

Very good, this seems to be the answer Borek: and I want you to come to.  However:

with this can it be explain like this:

if dosage per tablet is not  acceptable(from what i think)  it will result in every drug products will also having large deviation of weight between each other

and you're right back to your original point, which may be true, but doesn't follow logically from your conclusion.

Try to visualize -- consider a bowl full of black marbles -- 750 of them, and  250 white marbles.  Consider the black marbles are excipients (you know the definition of that, correct?) and the white marbles are medicine.  A person needs 25 white marbles for the medicine to work.  So there are, potentially, 10 doses in the vat.  So you pull out 10 separate piles of marbles.  What do you get if the white and black marbles are evenly mixed?    What do you get if the white marbles are all on one side?

So since non-uniform mix of powder affects weight and volume in powder,

Non uniform mixing affects the weight?  Where do you get this statement?  A pound of gold, and a pound of lead, melted together, are lighter or heavier depending on how well they're mixed?  That's not true.  Neither is it true for a medicine formulation.  Likewise, volume can be affected by mixing -- but that's mixing of air into the powder, not mixing of powders.

we could said that purpose of uniform mixing is to get the desired concentration of the drug products

Now see, this is exactly right.  But you didn't prove this, with your statements above.

[Lim]

Try to visualize -- consider a bowl full of black marbles -- 750 of them, and  250 white marbles.  Consider the black marbles are excipients (you know the definition of that, correct?) and the white marbles are medicine.  A person needs 25 white marbles for the medicine to work.  So there are, potentially, 10 doses in the vat.  So you pull out 10 separate piles of marbles.  What do you get if the white and black marbles are evenly mixed?    What do you get if the white marbles are all on one side?

Ok from this clue, I think I can explain about the concentration part:

If white and black marbles are evenly mixed inside the blender, the final product of each doses should most likely consists of 25 white marbles+ 75 black marbles which is the desired one, but white marbles are all on one side the final product would result in maybe some doses having more than 25 white marbles while some doses having less than 25 white marbles.

So from this can my answer be explain in this way by converting the marble example on what I explain on the top:
 
Uniform mixture of powders in production of final dosage form is to ensure that there is evenly distribution of active ingredient and excipients to achieve desired concentration for each final doses. With that it means like for example  in each particular doses it required 0.25w/v% of active ingredient with 0.75 w/v% of excipients to achieve desired concentration. If there is a non-uniform mixing of the final dosage form it may result in a particular doses getting more than/less than 0.25w/v% of active ingredient which is not the desired concentrations

[Arkcon]

That's a good summary of what I said, yes. 

[silverz89]

I think one thing that you might add is that proper blending ensures a consistent powder flow profile. Dosage consistency is also very important, but having consistently flowing powder can improve accuracy, boost cost efficiency and save a lot of time in the manufacturing development and production stages.

 With micro-dosing encapsulators i am familiar with, the dosing process equipment is  tuned with 6-8 control parameters.. it can be a headache to have to re-tune the parameters mid-production and that can be avoided with a powder that flows consistently (although powders that do not flow well to begin with are an entirely different discussion altogether)

[curiouscat]

What is a micro dosing encapsulator?

[silverz89]

@curiouscat, sorry for not getting back to you sooner

a micro-dosing encapsulator is a system that precision doses powder blends into capsules. the "micro-dosing" part of the name comes from the system being equipped with a highly sensitive balance.. accurate to at least .1mg if not more

here is a link to one such system (similar to what we have at our lab/ mfg facility)

http://capsugel.com/en/products-services/products/equipment/xcelodose/

[curiouscat]

@curiouscat, sorry for not getting back to you sooner

a micro-dosing encapsulator is a system that precision doses powder blends into capsules. the "micro-dosing" part of the name comes from the system being equipped with a highly sensitive balance.. accurate to at least .1mg if not more

here is a link to one such system (similar to what we have at our lab/ mfg facility)

http://capsugel.com/en/products-services/products/equipment/xcelodose/

Thanks! Very interesting!