Amount of active ingredient evenly distributed throughout each pill?

[PsychoActivist]

OK, SWIM doesn't know where this thread should actually belong - if it should be here or in chemistry so mods feel free to move it at your discretion.

Okay, so SWIM studies some Pharmacology but he is still quite ignorant about chemistry and production of drugs.

He had an odd thought just a minute ago and figured he would share it.

Take for example, a 7.5/500 Hydrocodone pill. Hardly any of that pill is Hydrocodone right? It's mostly Acetaminophen, fillers, and binders. Then somewhere in there, is this tiny little bit of Hydrocodone. I know a lot of people split pills in halves and take halves at a time (not usually 7.5 mg Hydro's but thats just an example remember?).
So I guess my question is this:
When the drugs are made, do the pharmaceutical companies have surefire ways of knowing and making sure that the 7.5 mg's of Hydrocodone in that pill are evenly distributed and mixed in evenly with the APAP and the fillers and binders? Is it possible that one half of the pill could actually contain, say, 4.7 mg's while the other half only contained 2.8? Or do they make sure is completely even?

Sorry just a weird random thought I got while I was on the toilet. (Isn't that when we all get our greatest revelations?)

Reputation Comments on this post:

Good question. Got me thinkin, and interested in actually researching the topic.

[Rhin]

SWIM thinks the same thing but about cigarettes and nicotine.

SWIM would think that the pills would be close to even but not perfectly even maybe a .1-.2 difference.

[Gradient]

PsychoActivist, the convention for pharmaceutical companies to identify a tablet that has been homogenized - and therefore equally distributed throughout the tablet - is called 'scoring'. This is a line that splits the tablet down the middle, or two lines into quarters. Though this isn't necessarily conserved across ALL pharmaceutical companies, it's generally followed.

Some tablets (pregnenolone or huperzine come to mind) are not homogenized, and therefore do not have such scoring. Generally, compounds that are highly potent and active at the sub-milligram level are not scored and evenly distributed.

In the case of a 7.5/500 hydrocodone/acetaminophen tablet, Swim has never seen a tablet that isn't scored (especially brand-name sources). The active components are therefore evenly distributed, and any discrepancy would be negligible as Rhin implied.

Reputation Comments on this post:

thanks for explaining the birth of pills

[PsychoActivist]

Thanks. SWIM figured the companies had some way of making sure it was evenly distributed and that if it was a little off, it would only be by about .05 or something ridiculously small like that. The way he said "4.7 on one side and 2.8 on the other" was rather extreme and just for the sake of clarity in the question.

SWIM had always known the line was called a "score" and he always just figured it was so the pill could be easily split in half. But what you are saying is that they use the score as a dividing line and split the mg dose, putting equal parts in each half (or quarter)?

Thanks for your answer. Most of SWIM's studying has been of Pharmacokinetics and Pharmacodynamics so he doesn't know as much about what the drug goes through before it enters the human body
But as of late he has been expanding his horizons.

[cra$h]

I'd imagine while making a pill with mulitiple chemicals, they would all be put in a big vat, tossed around, and then pressed, kind of like a chocolate chip factory.

[PsychoActivist]

Originally Posted by cra$h

I'd imagine while making a pill with mulitiple chemicals, they would all be put in a big vat, tossed around, and then pressed, kind of like a chocolate chip factory.

Thats how I had imagined it too. Thats why I thought there would be room for error. If it was "tossed around" then wouldn't there be chances that in some pills all the Hydrocodone made it's way to one side?

But the scoring thing makes sense.

[cra$h]

true. But if the particles are different sizes, they might mix pretty evenly. this is actually a really good question. Got me to look up, twist my face a little and raise an eyebrow.

[Jasim]

The USA FDA has regulations regarding generic versions. Generic versions must act just as quickly as brand name drugs and have a bioavailability (or bioequivalency) within 20% of the brand name drug (that's actually a pretty significant difference IMHO). So the active ingredient must be the same, but the inactives don't have to be. This can make a huge difference in the way the drug is absorbed. Furthermore, the bioequivalency of a drug does not equate to therapeutic effectiveness. For more info see: http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Brand name drugs are also likely to be standardized in that the amount of drug released per unit of time is consistent (barring special formulations). This means that a pill would have to be homogeneous. Generic medications generally don't make this claim, but some might.

I would hope that a score mark does denote some sense of equivalency, but I wouldn't count on it being exact in a generic form. It all depends on just how precise and accurate you want to be.


So....to more clearly address your question, in a brand name pill I would expect there to be a good chance of homogeneity. But I wouldn't have as much confidence in a generic pill.

Reputation Comments on this post:

	insightful data here, valuable resource that document is.
	good info, includes link

[Gradient]

Jasim,

Not to be confrontational, but the topic of this discussion had nothing to do with generic vs. brand-name tablets. There are undeniable differences between generic and brand-name tablets, but that doesn't change the fact that scoring is supposed to denote even distribution.

It seems as though the distinction that you're considering has more to do with the excipients chosen by the manufacturer than the distribution of the active ingredient. Such differences will indeed mediate metabolism of the active ingredient. Interesting information, however.

Here is a .pdf from the FDA that may communicate my point: http://www.fda.gov/cder/mapp/5223-2.pdf

Reputation Comments on this post:

good link maybe upload to the documents?

[Jasim]

Originally Posted by Gradient

Jasim,

Not to be confrontational, but the topic of this discussion had nothing to do with generic vs. brand-name tablets. There are undeniable differences between generic and brand-name tablets, but that doesn't change the fact that scoring is supposed to denote even distribution.

It seems as though the distinction that you're considering has more to do with the excipients chosen by the manufacturer than the distribution of the active ingredient. Such differences will indeed mediate metabolism of the active ingredient. Interesting information, however.

Here is a .pdf from the FDA that may communicate my point: http://www.fda.gov/cder/mapp/5223-2.pdf

Ah, thank you. I re-read my post and realized it does appear way off topic. What I meant was that differences in chemical composition and manufacturing processes could lead to differences in homogeneity. I meant the bioequivalency study to be a proven case where pills of the same dose of active ingredients differ in their effect. Why this is the case is still debatable, but I can't help but think that homogeneity could play a significant role.
I was assuming that this thread was dealing with the question of 'If swim breaks a pill and splits the dosing (among recipients or time frames), how does swim know that the effect will be similar based on similar sizes of pieces'. So to restate my stance, I would think that name brand pills would have greater consistency than generic.

BTW, thanks for that FDA paper. Very interesting reading!

[cra$h]

I thought it was pretty relevant. We're talking pills in general. If it was specific to one kind, well, then it would still be relevant. The topic being if pills are homogenized, and the answer being some have a greater chance than others, makes perfect sense. And thanks again for the insight.

But HOW do they homogenize?

[Gradient]

Crash,

PsychoActivist's initial title for this thread was: Amount of active ingredient evenly distributed throughout each pill? The articulated question was: "When the drugs are made, do the pharmaceutical companies have surefire ways of knowing and making sure that the 7.5 mg's of Hydrocodone in that pill are evenly distributed and mixed in evenly with the APAP and the fillers and binders? Is it possible that one half of the pill could actually contain, say, 4.7 mg's while the other half only contained 2.8? Or do they make sure is completely even?" No, we are not talking about pills in general, nor about taking pills in general. We are specifically discussing the distribution of active ingredients within tablets - even more specifically, the ability for a manufacturer to evenly distribute an opiate along with other agents within a tablet. The answer is - yes, the FDA regulates such production to ensure consistency among pharmaceuticals for the benefit of patients. There are likely deviations, but insignificant ones (hopefully, if the FDA is doing their job!).

If you read the PDF (from the FDA) that I posted earlier, generic pill manufacturers are legally required, under the Waxman-Hatch Act, to mimic the brand-name pill's scoring. If the brand-name manufacturer decides to alter their scoring, so must a generic tablet manufacturer. Additionally, the article states that scoring is to be the convention for patients to be able to modulate their dose; if the compound isn't produced at an ideal dose for an individual, one may be confident that by splitting their pill along the line, they will know the resulting dose.

Your question, one that I would consider to be quite interesting, belongs in a new thread. For example: how are tablets produced, how are excipients chosen, and how do such choices affect metabolism?

I find the topic of excipients to be quite interesting. For example, in the production of cannabinoid capsules, it would be far more appropriate to include a lipid-rich excipient rather than just stuffing some inactive herb to fill in the empty space. This is rarely the case, however, in medical dispensaries in California - and therefore warrants discussion. You should start a new thread - you have more repupation than I do, and would likely draw more attention from more informed people than I on the subject.

Reputation Comments on this post:

clear, helpful communication, please keep it up

[Jasim]

I'm assuming that such regulations exist beyond the FDA...in the UN and EU perhaps. But what about pills that can easily be obtained over the internet that are made in some remote lab in India or China?

What exactly are some steps or standard protocols that production facilities have adopted to ensure homogenization?

And I would be very interested in the follow up thread suggested.

[PsychoActivist]

It actually was in relevance to my question because we are talking about pharmaceutical companies in general. it doesn't necessarily have to be the pharmaceutical company that patended the brand name. It can be in reference to say a company like "Watson" who makes Hydro's. Though they are not the ones who patented the name "Lortab".

I feel it is Jasim's was relevant because I was not just asking about the patented brands and if the generics are made differently I would like to know about that as well.

[Gradient]

PsychoActivist,

If swiy was curious about pharmaceutical companies in general, perhaps swiy should've began with a more general topic for the thread - this would have facilitated a more general response from knowledgeable individuals. I was simply trying to provide you with the best answer for your question. The question has been answered several times; I don't know how else to answer the question that swiy had initially posted other than YES, companies are able and required to evenly distribute active ingredients if their tablets are scored. Differences between the distributions of the same compounds by generic and brand-name producers are negligible and effectively illegal. Again, swiy's initial post had nothing to do with the differences between brand-name and generic brands, only the distribution of active ingredients. To begin discussing other topics within this thread defeats the purpose of a thread. This thread had devolved dramatically, and I hope it ends here.

[gilligan_911]

hey wow! swim was just thinking of this. so the 'scored' pills have it equally distributed throughout, but what about the case of pills like Oxycontin? does a 1/4 of a OC 80 reall have 20mg of oxycodone or might some of the filler/binder been tossed around inside and only say 15mg ended up there and 25mg on another 1/4 piece?
swim has always been interested in this because when he and a friend split a pill were they both gettin the same amount or was one getting more? (some deep insecurity issue probly :P) and swim uses a pill cutter that is extremely accurate, once swim got paranoid and went about cutting pils in half with it and then weighing (.0001 scale) both sides to get an accuracy on the cut. and it turns out it was only ever off by .05mg which is pretty good swim surmises.
anyway off topic, whats the deal with non-scored pills? you swimmers think the active ingredients are equally spread out?

[Jasim]

Originally Posted by gilligan_911

anyway off topic, whats the deal with non-scored pills? you swimmers think the active ingredients are equally spread out?

They should be. Were they extended release?

[Potter]

Jasim: As to pharmacies in S.E. Asia, they are probably lacking in the department of protocols. Frankly you have no idea what is in a pill like that, it might be inert, it might even poisonous. There have been numerous counterfeit pills out of that area and they should be avoided. As to your question specifically, who knows?

[Jasim]

^ That's true, I was only considering authentic name brand pills. But really anyone with a pill press can make pills. And pill presses can be purchased online.

[gilligan_911]

Originally Posted by Jasim

They should be. Were they extended release?

yes, they're brand name Oxycontin 80mg pills, green with OC and 80 on either side. it would be interesting to know how they get the active ingredients to be evenly spread, maybe they do layers like filler/binder/Oxy/filler/binder. interesting things these pharmaceuticals are

[Jasim]

^ If it's a good pharmaceutical company, then their operating procedures should have explicit instructions for ensuring homogenization. Even without such procedures, solutions (or large batches of powders with thorough mixing given particulate size is roughly equivalent) should become evenly dispersed due to La Chatlier's principle of equilibrium.

EDIT:
I'm sorry, I misunderstand whether or not they are extended release. Extended release tablets are made a bit differently in order to slow deterioration and release of the active constituent. All extended release tablets I know of are constructed in such a way as to make them circularly equivalent or radially symmetric as to dispersion of active ingredient. So if swiy is carefully cutting the pill in a radially symmetric way, then the pieces should be roughly equivalent as to dose.

[gilligan_911]

thankyou! SWIM feels much better hearing that sort of information. its those little bits of knowledge that keep SWIM on DF deep into the night searching out answers.

Its funny you should mention Le Chatlier, SWIM is doing equilibrium labs right now