I’m going to try to be concise, but this may get complicated.
When you take any medicine, whether pill or liquid form, the active ingredient has to get in there somewhere, obviously. I’m wondering where the chemical makeup is made into a form that can become an ingredient.
For example, I’m on 3 scripts. One of the dogs is on cephalex for an ear infection.
Of the 4, 3 are in the form of a gelcap with the contents in powder form, and my 3[sup]rd[/sup] is in tablet form. What got me curious are the 3 in powder form.
They are all vastly different in both drug class and what they do. Yet the powder all looks the same. (As the tablet is, I’m sure, but with different buffers and fillers) So the process of making the active ingredient must be somehow the same.
One of mine is Strattera, with the active ingredient atomoxetine hydro-chloride. OK, so we have the name of the chemical compound that gives the benefit. But how is atomoxetine HCl made in the lab? I assume they don’t just have a big cement mixer and fill it with the right parts of each chemical and hope for a good batch.
I remember a bit from chemistry classes at the U but never got so far into it to even touch on this trick. If anyone has info on how this is done, please explain it to me like I’m 8 years old. I really want to make sure I understand the process. It’s been bugging me for years.
Chemical Engineer checking in. That is actually very close to how it is done, as it happens. I’m not familiar with the production specifcally of Strattera, but most drugs are produced in batches, often in what you might call a vat albeit with well defined steps. There would be very little “hoping”. Each process for each drug would be quite different so unless you actually know how it’d done, just knowing the end result isn’t enough to know the process, which is quite proprietary.
Yes, active ingredient amounts in pills are on the order of mgs, but the actual pills weigh grams. Compare a multi-vitamin and all they stick into it with an anti-histamine pill. The MV is going to be larger, but not comparatively. An anti-histamine pill that was all active ingredient would be too small to take.
Raygun99, thanks for the link. I knew all about the fillers and such and how pills are made, but didn’t know how the active ingredient itself was made to add to the filler.
Sometimes the answer is so obvious you can’t see it. :smack:
Different drugs are made in many different ways. Some might be as simple as the cement mixer method, others (probably not that many these days) are distilled or chemically extracted from big piles of tree bark/insect parts/monkey pancreases. Many are made by specially genetically engineered bacteria living in a vat. Heck, zinc and lithium are mined/smelted. Of course, the material you extract/mine/get from the vat will probably then be run through a few more chemical steps (using cement mixers or what have you).
They all look the same because a) most of what you see is filler anyway, and b) really, almost everything solid looks the same when dried and ground up finely: white powder.
The fact that a chemical is a white powder does provide some very basic information about its composition, though it mostly tells you what sort of compounds the chemical is not: white powders usually do not contain a metal, and they usually do not contain extensive conjugation (alternating double and single bonds, either in a ring or a straight chain). Other than that, it says very little about the compound.
It’s very difficult to explain how pharmaceuticals are prepared in a simple, easy-to-understand way. Actually, it’s even difficult to explain in a very detailed and complicated way without being able to draw structures. To figure out how to make a given chemical, organic chemists start with a drawing of the final product. Then, they look for simpler chemicals within the structure of the final product. Almost all drugs, no matter how complicated their structure, can be made by linking together and modifying simple chemicals that can be easily and cheaply purchased. Essentially, they work backwards from the final structure, and arrive at a series of reactions that must be performed on simpler chemicals to get the final structure.
Some drugs can be made in a relatively small number of steps; some require dozens or even tens of steps. (Drugs that require 20 or 30 steps are not unheard of.) Strattera is relatively simple and requires about five steps. Again, it’s very difficult to be explain how it’s prepared without being able to draw structures, and it’s difficult if not impossible to understand how it’s made without knowing some rather advanced organic chemistry.
You can see the chemical structure of Strattera here. An abstract describing the synthesis can be found here, if you know what the Stille coupling and the Mitsonobu reaction are. (It’s possible to figure out how the drug is prepared by reading the abstract, but organic chemists usually think in terms of drawings. The article would include several diagrams that summarize how the molecule is put together.)
Whille Roches’s points are very well taken, I think that there’s some confusion, both between duffer and those replying, and within duffer’s own understanding.
So. Some pharmaceutical chemicals (aka active ingredients, aka drugs) are purely synthetic – that is, starting with the basic structures found in, say, petroleum, one performs a series of chemical reactions to get the final product. Many drugs are actually produced by plants, molds, or bacteria: some merely need to be extracted, while others must be chemically modified to be useful. An increasing proportion of drugs are produced by genetically engineered organisms. Following the crude production, most drugs need to be refined – by recrystallizing from a solvent, by extracting from one solvent into another, by large-scale chromatography, etc.
This is the “white powder” stage. Most finely divided materials scatter light of all wavelengths, and thus appear white. A relative few will have the special properties needed to selectively reflect vivible wavelengths of light, and these will be colored.
The material in a tablet may be mostly binder, filler, and other intert material. These materials are selected to make sure that the tablet will remain in one piece until it’s taken, and will then dissolve and deliver the drug effectively. On the other hand, a tablet of extra stength Tylenol contains 500 milligrams of acetaminophen, more than half of the weight of the tablet.
The material inside a simple capsule is often pure or nearly so. Antibiotics are often delivered in doses of several hundred milligrams – I’ve taken 1.5 gram tetracycline capsules, and that’s about as big a pill as anyone wants to swallow.
I hope that fills in the gaps, feel free to ask more questions.
Since the active ingredient is so little, could it be concievable in the near future to get “tailored drugs” that combine several active ingredients in one capsule for people taking multiple drugs at the same time?
A few more things, although as a molecular biologist I’m not really qualified.
If you look at Roches link to the picture of Strattera, you will see that there is a carbon backbone coming off the phenyl ring (the hexagon in the lower right connected to the zig-zag bar). Coming off of this is an oxygen, connected by a dashed wedge. This is a special thing in drug design – the description tells us that it is the R-isomer, and the dashed wedge indicates that this is a stereocenter. This means that there are two mirror images of the drug possible (the dashed wedge indicates that the O is pointing away from you, the opposite version would have the O pointing towards you) and atomoxetine is only one of the two. Getting only one of two stereoisomers is often a tricky thing. Often times, a medicine will consist of two forms of the stereoisomer (the R and the L in this nomenclature), and only one will be active. Sometimes, the other has bad side effects, as was the case for thalidomide. Sometimes, the other will be harmless. Often times, a drug company will remarket the active stereoisomer after the cheaper mixture goes generic. Stereoisomers are problematic and often add a lot of cost to drug development.
A lot of drugs, for instance your cephalexin (a first generation cephalosporin), are variations on a theme. Cephalosporins were originally developed as novel molecules containing a specific kind of group, a beta-lactam group, that is the business end of penicillins. Cephalexin was one of the first. There are umpteen kinds of penicillins, all with different properties, that have come about as chemical engineers have modified the structures and added junk on the sides of the molecules to get these changes. They have done the same with cephalosporins. You can see this here.
Yeah, you start with a cement mixer, but like any process, you end up having to isolate the good stuff away from 99% of the leftovers. There are hundreds of ways to do this, but commonly, people use filters, dissolving away the good stuff or the bad stuff while leaving the other stuff behind, and fractionating the mess to isolate what you need. This often uses a process called chromatography. There are a bunch of kinds of chromatography, but the simplest way to understand this is the old high-school science experiment of writing with a colored marker on a coffee filter and then wetting one side of it. The different inks in the marker dissolve at different rates in the water and stick at different levels to the coffee filter. This leads to them separating out as the water makes its way through the filter. Same thing with isolating a drug – if you know how it is going to stick versus dissolve, you know where it will be. Obviously chromatography done by biotech is a lot more complicated (gas, liquid, HPLC, solid phase, whatever, haven’t done chromatography in a long time), but it is the same principle expanded.