Thursday, November 20, 2008

Glove compartment research

Good news, we have been analyzing the glove compartment samples over the course of this semester and I think we are seeing some interesting results! Thanks again to all of you who helped us out. As soon as we have numbers that will make sense, we'll share them with you.

In other news, we just presented a poster at the Southeast Regional Meeting of the American Chemical Society on our other Ibuprofen research. At this time we think that there are some inactive ingredients that promote degradation of ibuprofen, especially one called polyethylene glycol, which is also called PEG. Our results to date show that all tablets that contain PEG degrade more quickly than those that don't.

A student who came to see our poster and asked a lot of questions brought up an interesting point. She works in a pharmacy and they always tell people that generics are the same as name-brand medications. That is true for the drug molecule used, but the inactive ingredients can be very different for different manufacturers. So if the inactive ingredients result in different amounts of degradation, generics can be considered different in that way.

We were offline for awhile, but now we have a new instrument and we are moving ahead with the research! Thanks for your interest!!

Wednesday, August 27, 2008

We're back!

Another extended break in blogging because, unfortunately, our instrument (HPLC) broke and so we could not do any more analysis. That kind of took the wind out of our sails for awhile. But, the Fall semester started yesterday and so we are gearing back up. Thankfully, my National Science Foundation grant was funded (yay!) so we will be getting a fancy new HPLC very soon.

Also, I have another student working with me this semester, Sabrina, who will be analyzing our glove compartment samples. They are due to be removed from glove compartments around the country on Labor Day and sent back to our lab. One of the first things we'll do is take pictures of these samples to see if their physical properties changed at all. Corby says the ones he has in his glove compartment (in Charleston) look different.

We had one casualty - our samples in Gainesville FL were accidentally thrown away! I know how hot my car used to get in the parking lot of UF in the summer, so I am sorry we will miss out on the very cooked samples. However I am hoping that the Charleston and Albuquerque samples will be interesting.

So stay tuned for those photos and updates. We are always interested in more input and questions.

Monday, June 30, 2008

Will expired pills hurt you?

Sorry for the extended break, we have been vacationing and are getting back into the lab today.

Shannon left this question, which is a good one. The answer is, it depends on the pill.

In the studies of ibuprofen done over the past 30+ years (it's been around a long time!), we have learned that one of the impurities is considered toxic. For this reason, it impurity can't be more than a tenth of a percent of the dose (for example, if you take 400 mg of ibuprofen - 2 pills - you should not be ingesting more than 0.4 mg of this impurity). But that is the requirement for the manufacturers before it is shipped out to stores. We know that it also increases over time as a degradant. This is why ibuprofen pill boxes say to store it at certain temperatures and humidities. So if you don't store it at room temperature, how much will form over time? (we'll get an idea of this from our glove compartment study.) And is that amount enough to make you sick?

I have not found any studies in the literature about the amount that will make you sick. I want to talk to a toxicologist, because I know that the FDA is a lot stricter these days about the amount of a toxic impurity that can be present in a pill. So if ibuprofen were a brand-new drug today, would they say it is OK to have 0.1% of this impurity in it? I'm not sure.

I hope that answer is not too technical and boring.

Corby and I are observing that pills that contain certain inactive ingredients seem to degrade faster than others. I am not ready to tell you what that is yet, but if we are right, it will be interesting and hopefully get us published in a scientific journal. When we have some solid results, we'll share that with you.

In my opinion, if a drug has been on the market a long time, the impurities in it could not be too bad. Otherwise you would hear about it on the news and it would get yanked from the market. However, it is still not good to ingest more toxic things if you can avoid them. This is why I suggest storing medicine at its recommended storage conditions and throwing out expired medicine.

Also, the bathroom medicine cabinet is probably not the best place for storing it, since it gets pretty humid in there! I think a high shelf in the kitchen (away from the stove!) is a good place. But I will admit that most of my medicine is in the bathroom cabinet, because Matt does not like to see all that medicine.

Wednesday, June 11, 2008

More on expired medicines

Krista left this in her comment and I think it is good enough to share on the front page!

http://consumerist.com/tag/prescriptions/?i=5015011&t=cvs-in-pen

That is an extremely disturbing story.

I bought some more ibuprofen yesterday at Walgreens and the box says to store it at temperatures less than 40C. However I think most people do not read the fine print or else don't worry about it. Including CVS managers.

A lawyer I know (concealing the identity!) has told me stories about people prosecuted for selling pseudoephedrine beyond the amounts that are now legal, and has heard the excuse that if it was really bad for people, the government would not allow it to be sold. So maybe this is the common thinking. If Ibuprofen that has been in my glove compartment for over a year is not safe, the government would not let me buy it (and/or put it in my glove compartment). Or they would shut down all CVS stores with broken air conditioners.

One of the students that I am working with this summer told me that a friend of his took expired Adderall and had a heart attack. I did not inquire further to confirm or disprove this story but if anyone else has proven stories or urban myths to share, please do so. I am so interested in these stories.

Glove compartment temperature over course of day


Yesterday I took the temperature in my glove compartment over the course of the day and graphed the results. I moved my car every few hours so sometimes it was in the shade and sometimes in direct sunlight.

The highest temperature was 169 degrees Fahrenheit! Yikes.

Tuesday, June 10, 2008

How does storage temperature relate to expiration date?

Most of our ibuprofen samples recommend storage at 20-25 C (68-77 F). As far as I can tell, most of them have a shelf-life of 3 years, which means that the expiration date should be 3 years from the date the pills were manufactured.

I can say that at Pfizer, when we set an expiration date, we tested the pills as they were stored for some length of time (for example, 3 years) and if they passed all of the quality tests, we set an expiration date of 3 years. That does not mean that they were of poor quality after 3 years - we just stopped testing them at that point. So, are your medicines still OK after the expiration date? Well, the answer is, it depends. I would be more wary of prescription medications after their expiration date than medicine I bought over the counter, but the best answer is, throw it away after its expiration date.

The expiration date is directly related to the recommended storage temperature.
Anyone who has taken chemistry knows that one way to speed up a reaction is to heat up the sample. So if the medicine is "expired" after 3 years at room temperature, it will be "expired" quicker at a higher temperature.

The relationship is given by what is called the Arrhenius equation:

k = Ae^(-Ea/RT)

But, let's skip the math and get straight to the answer: If a medicine has 36 months of shelf life at 20-25 C, it has 30-40 days of shelf life at 70C. Roughly, you can half the shelf life for every additional 10 degrees Celsius.

Remember, these are rough estimates, but you can see:

20C: 1080 days
30C: 540 days
40C: 270 days
50C: 135 days
60C: 68 days
70C: 34 days

For those of you interested in the math:
A good average value for Ea of this type of reaction is 15 kcal/mol (according to the pharmaceutical experts). The range is 12-18 kcal/mol.

Temperature in my glove compartment

Yesterday I put the glass thermometer in my glove compartment at around 3:00 pm and checked it at 5:00 pm. My car had been parked in my driveway in direct sunlight.

The temperature in my glove compartment was 65 degrees Celsius at 5:00, corresponding to 149 degrees Fahrenheit. Wow! That is hot. I'm going to check it every two hours today.

This morning, it was only 26 Celsius at 7:00 am. So, that is less than half of what I saw yesterday. This reminds me that the pills in our glove compartments are not only getting really hot, but are actually cycling between hot and cool every twelve hours or so. At Pfizer, we did this kind of cycling study with medications, especially liquid forms, to see what might happen as they are shipped. Such as, if they got really cold in the cargo hold of a plane, and then warmed up in the back of a truck. You try to package things to keep a constant temperature, but we all know that it sometimes does not work out that way.

We are, according to the news, experiencing an East Coast Heatwave through Wednesday. And it is only June 10, so it is not really summer yet. I can just imagine the chemical reactions going on in those tablets.

Monday, June 9, 2008

Temperatures across the country

Albuquerque: 69
Montrose CA: 85
Colorado Springs: 62
McMinnville OR: 55
Minneapolis: 71
Gainesville FL: 89
New York NY: 92
Cleveland TN: 90
Charleston SC: 83

I am glad I am in Charleston and not McMinnville or New York. I can't believe it is actually one degree cooler in Gainesville FL than Cleveland TN (my hometown).

I put a digital temperature probe in my glove compartment at noon today. When I checked it at 1:45, the digital screen had turned black because it was over the max of 50C, which is equal to 122 Farenheit. So, it is hotter than that in my glove compartment right now. And it is (according to weather.com) only 83 degrees right now in my zipcode. My car is parked on the street in direct sunlight.

Tomorrow I'll put an old fashioned glass thermometer in my glove compartment and try again. This requires a scientific thermometer, because drug-store variety only go up to around 110 F. If any of you have a scientific thermometer, feel free to take the temperature in your glove compartment at any time. Otherwise, I will just correlate the temperatures here in Charleston to my glove compartment and we can use that to approximate what is going on in other climates.

Tuesday, June 3, 2008

Who made my pill?

I just found a website that is my new favorite. We have been buying generic ibuprofen pills at several drug stores, but almost none of the labels indicate who actually manufactured the tablets. From a chemistry point of view, this is important to us. This website will tell you who manufactured your pill, based on what the pill looks like:

pharmer.org

Here are all of the ibuprofen pills:
ibuprofen pills

All of the pills that we have bought so far are on this list.

As you can imagine, everything in the pharmaceutical industry is proprietary information, so if you call these companies to ask questions, they will not tell you anything. I would like to find out where these generic tablet manufacturers buy their ibuprofen (the pure drug) to put into the tablets, but so far, no luck with that.

This website seems like a really good resource for consumers, because we all deserve to know who is making our pills, in my opinion.

Monday, June 2, 2008

What do Ibuprofen pills from other countries look like?



Here are the packages and pills that we have received so far from other countries.

Green from China, hot pink from the Czech Republic, white from Australia, white from Argentina, blue from Australia, orange from Japan, and orange and white capsules from China. Thank you Ben, Iveta and Uli, and Justin for procuring these for us!

I like the hot pink ones the best, but ethically I like the white ones from Argentina the best, because they actually look like medicine rather than something pretty that Simone might mistake for candy (!) Also, all of these except for the Japanese ones come in a blister package (clear plastic with foil on the back), so they are definitely not child-proof. And the Japanese ones come in a glass jar with a regular screw-top lid, so, also not child-proof.

We are doing experiments on these (along with about 8 US brands, including Motrin and Advil). The experiments include exposing them to high heat, high humidity, and light to see if they degrade and what chemicals are present as a result of the degradation. We are already finding some interesting results that we can report on in a scientific journal, which is exciting to us. Corby will have something nice for his resume! However, our instrument (an HPLC), which actually does the chemical analysis, is currently not working so we are on hold for the time being. We can hardly wait for it to be back in working order so we can get lots of data and numbers to start crunching in Excel.

We will report more on some of Corby's specific summer project soon, and show you an example of what our HPLC data looks like.

Please feel free to leave us a comment and let us know if you are reading, and what kinds of questions you have! It is hard for us chemists to think like non-chemists and know what normal people want to hear about.

Tuesday, May 27, 2008

More glove compartment research

The other glove compartment project we are working on involves a pill box like the one shown below, except that each compartment contains not only ibuprofen pills but also a couple of aspirin pills. This idea came from my mother-in-law, Leslie, who was telling me about someone she knows who keeps all of their medications in one container. I am sure this is pretty common for people who carry around multiple types of medicine.

The chemical name for aspirin is acetylsalicylic acid. When it degrades, the major product is a similar molecule called salicylic acid. (It also relieves pain, but not as effectively. Hippocrates wrote in the 5 B.C. about chewing willow bark for its therapeutic properties - that is a source of salicylic acid). When aspirin breaks down into salicylic acid, it also releases acetic acid. Acetic acid is what makes vinegar smell like vinegar. So, if you have ever opened a bottle of aspirin and smelled vinegar, that is why. Here's the reaction:



So, why are we putting aspirin and ibuprofen together in the glove compartment? We are wondering if the acetic acid released from the aspirin will cause some accelerated degradation of our ibuprofen. That is, if ibuprofen degrades in the glove compartment due to high temperature, will it degrade even more if there it is exposed to acetic acid at the same time?

If you have any other ideas on medicines that people might carry around in the same container, let us know! Aspirin is a good one because we know that the acetic acid is formed and emitted by the tablets.

If you have any old vinegary aspirin in your medicine cabinet, feel free to send it to us! It's a great example of drug degradation for the students, because you can actually smell it - you don't need a complicated chemical analysis to detect the presence of acetic acid.

Glove Compartment research

The idea for this experiment came from Corby, who told me that his dad keeps ibuprofen in his glove compartment of his car. I started thinking about how hot it might get in a glove compartment, especially in Charleston in the summertime. So we decided to package up several brands of ibuprofen and send them to people around the country to store in their glove compartment over the summer. The packages look like this:


There are seven brands of ibuprofen pills, including name brand (Advil and Motrin) as well as several generic brands (Walgreens, WalMart, Costco, etc.)

The packages will be left in the glove compartments from Memorial Day weekend until Labor Day weekend. (To our participants, if the packages are not in your glove compartment yet, that's OK. Just let us know what day they are put in.) Then our participants will send them back to us for analysis.

We know from our lab experiments that ibuprofen pills that are exposed to heat and humidity over time will degrade. In the glove compartments, we only expect them to be exposed to heat, because the package will protect them from high humidity. So we don't really know what might happen. We'll be monitoring the temperatures of the locations, and we will note which cars spend days and/or nights in garages and which ones don't. Here is a map to show you all of the locations across the country that we are lucky enough to have access to glove compartments.

Tuesday, May 20, 2008

Thanks for helping us!

Thanks again to those of you who are helping us with our ibuprofen research. The purpose of this blog is to share information and show you some pictures of what we are working with. We have gotten ibuprofen from Argentina, France, China, Australia, Czech Republic and Japan. We will share pictures of these as we begin preparing them as samples. If you have any contacts in other countries who might be willing to send us some ibuprofen, we would be thrilled to have samples from as many countries as we can get! The more exotic, the better.

This is my favorite package, from Japan. It was sent to us by Justin Wyatt, another C of C professor, who has been in Australia for the past year on sabbatical. Thanks Justin!



It reminds me of the package of soap with Homer as Mr. Sparkle:



I took Japanese in college, and while I don't remember much, I can read the characters (when I have an idea already of what they say). Japanese characters like these stand for a syllable rather than a single letter. The yellow letters on the ibuprofen label say "eye-be-be-ro-fe-n" and the Mr. Sparkles label says "mi-su-ta-a sa-pa-a-ra-ku". Japanese uses 3 alphabets, and these characters are from the alphabet they use for words that are not Japanese. Like ibuprofen and Mr. Sparkles.

Homer seems to be saying "ha-ku-u ku-ri-i-tsu," I could be wrong about that, since it doesn't make any sense. Does it?

I just thought I would share that with you!

Working with me on this research is Corby Harris, who will be posting to the blog as well. You can check back periodically for new information and interesting tidbits such as the one above.

Soon we will have a post concerning our Glove Compartment research, including information about the samples that we are sending to many of you around the US. We hope you will receive them by this weekend; please put them in your glove compartment when you receive them and you can email us to let us know when you get them in place at:

coryw@cofc.edu


Thanks again for your help!