When I was young, I knew of only two ways to get a medicine: either orally (pill, capsule, or liquid, presumably determined by how soluble the stuff was), or by injection (I suppose this was when the digestive tract is harmful to the medicine).
Nowadays there are a zillion other ways. Some drugs get breathed in. Some are on an adhesive patch and get magically absorbed through the skin. I just saw a commercial on tv for an osteoporosis drug (sorry i forgot the name) which is administered once a year via an IV that takes 15 minutes.
I’m just curious how they figure out the best way to give these drugs, and their dosages. For example, I suppose that administering this drug orally or by patch or injection did not work well; how did they figure that an IV was a good idea? Also, it seems obvious to me that to establish a once-a-year dose, the clinical trials (comparing that to a twice-a-year or every-two-years dosage) must have gone on for at least 5 years or so.
Partly it is based on similar medications and then they test various ways using clinical trials. They want to find easier ways so that people will use the drugs, some people get drugs and don’t use them if they are too hard to use.
Inhaled insulin was approved and they thought it was going to be a good idea but nobody used it because it was too complicated to use. Also the container for it was very large and hard to carry around. It sold so poorly it was removed from the market.
There have been nose drops and eye drops since forever too.
Probably also anal suppositories.
And women have vaginal suppositories, though I don’t know how recently they’ve been invented. My wife needed those not too long ago. It wouldn’t surprise me if they’ve been around awhile too.
A lot of it goes into what the drug molecule looks like, its acid/base character, and general knowledge of chemistry. Drugs can be lipophilic (loves fat), or hydrophilic (loves water) which if you know that you can make drug models of where it will be stored or excreted in the body. Also, knowing the acid/base character of a drug molecule, and its pKa will let you know if a drug will be ionized/unionized and protonated in different parts of the GI tract letting you guess where it will be absorbed into the body, and where if it will be excreated by the kidneys.
These guesses are then tested in animal studies, and then if they know what it does in animals, they can do human trials.
As Huerta88 said, a lot of this is done in the study of pharmacokinetics and pharmaceutics.
Some of it is probably market-driven as well. If people complain of stomach upset from a drug, there will be more interest in exploring alternatives to pills. If consistent dosage is important, there will be more interest in long-lasting ways to administer the drug.
Mostly right; most of the chemistry of drugs is actually just done in a test-tube; there is no point using animal models just to see if a drug will be degraded in pH 1.2 or 6.8 or 7.2 solutions (the three generalized GI tract pHs).
I did not work in drug discovery or formulation, but this is a very broad description of my understanding of the process.
Once a molecule is identified as a drug candidate in very small scale in-vitro tests either at a company’s R&D labs or even in a university research lab, the next step is to figure out how to get it into the person or animal (veterinary drugs) it is designed to treat. Big Pharma either does this in-house, or contracts it out to Contract Pharma companies, but either way, things are basically the same.
The drug will be tested for stability in acids, bases, high and low temperature, water reactivity, light reactivity and stability in mixtures with other common excipients, such as lactose, methyl cellulose, EDTA, BKC whatever they think might end up in a pill/capsule/injectable/suppository/cream/ointment/nasal spray/eye drop/etc with the drug candidate. Once all of this data is collected, Formulation Scientists take over, and start figuring out what the best drug delivery method will be. These studies will help determine the most likely route of absorption of the drug into the animal/human as well.
If, for example, the drug candidate was determined to be suitable for a pill, designed to be absorbed into the blood stream via the upper GI (which I think is pH 6.8…been a long time, don’t quote me on that!) but the drug isn’t super stable at 1.2 (stomach acid), then the Forumlation guys will start to come up with a variety of pill recipes with coatings designed to survive through the stomach but expose the inner core once the pill reaches the intestine, or whatever. Usually several prototype formulations will be created, and these will be lab tested and often weeded down to a handful of possibilities, and then animal testing will begin. I worked on one project lab testing a drug that began with 28 formulations, and we brought it down to 7 before animal testing was started. The different formulations might be mostly identical, but with 28 vs 30 vs 32% of a given excipient, or they could be quite different with totally different components. IME, usually the former.
The lab testing will involve stability tests (potency and impurity over long term at different storage conditions…search my name and “stability”, I have posted about this before) and very often dissolution profiles, in which the release of the drug at different pHs over a certain amount of time is measured. Some drugs are designed to release 95% of the drug in 5 minutes, others need to only reach 75% after 1 hour, whatever… there’s a lot of variety in this depending on what the drug is for and where in the body it is intended to be absorbed.
The animal models will then provide data regarding if the drug is being delivered, how long it takes to get X concentration in the blood, etc. I’ve never worked in animal testing, so there’s a lot here that I don’t know.
There are literally years of lab and animal testing to see whether the drug behaves as expected in terms of delivery. This is also an early time for determining basic toxicity and overdose levels.
All of this is tracked and approved by the FDA or equivalent agencies, and sooner or later the drug will progress through the various phases of clinical trials (from rats/mice to dogs/monkeys to testing in healthy humans, to testing in symptomatic humans, to large-scale testing, etc) and make it to market or, most likely, the drug will be found to be too toxic/have weird side effects/not be effective/whatever and the project dies along the way.
It really has been too long since I thought of this stuff, let alone worked in any related capacity, so I’m sure I’ve over-generalized and possibly even mis-spoke in that description, but I hope it was somewhat helpful (and somewhat coherent!)
Oh, I suppose I should add that the first choice is always a pill, because it’s incredibly easy to make. Capsules are good for quick-release in the stomach since they tend to dissolve more easily than binding agents in pills. Something like a nasal spray/inhaler or eye drop is used when it is known that the drug can be absorbed through the mucous layers of the targeted organ (respiratory tract/eye) and a direct delivery to the needed site is usually considered better than an indirect one. Intra-venous/injectables are for rapid action, though some may be pharmacologically persistent in the body and therefore offer a therapeutic effect for a very long time (weekly, monthly, etc). These are usually simple formulations (water, drug, stabilizing ingredients) but require sterile manufacturing which is very expensive and difficult to acheive. Suppositories offer a rapid and direct delivery to the blood stream and are a good alternative to pills when the patient cannot take a pill (when they are throwing up a lot, or certain stomach ailments or comas/vegetative states, or just too young…giving a suppository to an infant for a cold is a heck of a lot easier than giving syrup or pills!)
You did a pretty good job, I’m sure it took you a long time to write that Pretty much everything you said agrees with my pharmaceutics classes. I was just trying to be a little more broad (plus I’m writing this in class, and didn’t have much time )
One thing I will add is there are some structural features of certain drugs that limit the way it is administered. For example, Insulin is a polypeptide so it would be degraded by the enzymes in the GI tract which is why it has to be administered parenteral (shot, IV, etc) because it is a polypeptide and would be destroyed by the enzymes in the GI tract, other examples include vancomycin and other aminoglycocides. There are also some drugs that are have low bioavailability (how much of the drug is available) when given orally because it is even absorbed by an active transport mechanism in the intestines that can be saturated, or because it is extensively metabolized by the liver during first pass.
Oh, and a slight nitpick… It isn’t pills, it is tablets. A pill is an old dosage form from way back that isn’t used anymore. That doesn’t stop people from referring to tablets as pills, but since this is the SDMB, just trying to be accurate.
A pillis an old dosage form from when pharmacists had to make each dosage form personally (aka didn’t come from a big manufacturer). It is made by taking the active ingredient and grinding it with a mortar and pestle with a dough like substance. They then took this dough and rolled it out on a board (called a pill board by all chance ) into a long cylinder. They then cut this down into individual doses and dispensed it.
A tablet on the other hand is made by taking the drug and excipients (the whole thing is a powder) and pressing it in a mold with such force that it is forced into a solid. This is done with a machine. It was actually pretty neat to watch when we made them in pharmacy school.
Having worked in a BigPharma lab, though, I can attest that the word “pill” is used informally pretty often, though it is true that “tablet” is the term found on paperwork.
I’ve never taken any pharmaceutics classes, so there are a lot of specifics and technical details that I don’t know. I just worked as an analytical chemist and asked enough questions/was given enough early-stage projects to work on to grasp some of how the whole process worked. I briefly considered applying for a job in the Formulation department at my first company, then we decided to leave the province and eventually I chose to change careers. I’ve always found this stuff way more fascinating in theory than in practise!
Thanks you all for your very enlightening responses!
I figured the “rapid action” part, but – intuitively – I figured that such medications would also get used up relatively quickly. That’s why this commercial for a yearly IV surprised me so much. But I’ll take your word for it that they’ve done their research, and that this one is “pharmacologically persistent” for such a long time. It really surprises me, but hey, that’s why “It’s taking longer than we thought”.
There are a couple ways to make parenteral drugs long acting. The most common way is via a depot injection where the drug just takes awhile to diffuse out of the injection site to the site of action. I haven’t actually heard of the osteoporosis drug in question, but it doesn’t surprise me since most osteoporosis drugs (Fosamax, Boniva) work by being incorporated into the bone, and inhibit the action of osteoclasts (the cells that break bone down). Since they are in the bone, it takes awhile for them to dissipate.
And, your welcome for my responses… It is actually nice to be able to use some of the information that I’ve learned throughout pharmacy school… and not be graded on it
And some of it may be cultural or perhaps local market conditions. In Scandinavia the most common form for inhaled asthma medications is dry powder inhalers whereas in most other markets spray inhalers are more common.
One anecdote (for which I have absolutely no supporting evidence) is a professor I had who described the cultural differences between various European markets when it comes to modes of administration. According to this professor Italians seem to prefer injections more than other countries and apparently suppositories are more popular in France.
I don’t know about France, but I can tell you that for one company I worked for, who manufactured suppositories for colds/allergies, their largest market by far was in Québec. I spoke to one sales rep from Alberta who could never figure out why the company kept sending him samples of this stuff, because it was damn near impossible to sell, except for the infant ones, and even that was generally to hospitals rather than pharmacies!
Pretty much everything you said agrees with my pharmaceutics classes. I was just trying to be a little more broad (plus I’m writing this in class, and didn’t have much time 
) into a long cylinder. They then cut this down into individual doses and dispensed it.