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!

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.