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Posted: Tue Nov 08, 2005 10:31 am
by geoffbruton
Hi Joel!

This is not really my area, but I've reviewed your questions and concerns, and thought I would try and give you some input. I hope this helps!

First of all, you are absolutely right in trying to maintain body temperature during your experiment. If the solution cools, the time taken to dissolve the tablets will increase - and besides, the human body should not cool down, unless the person has stopped breathing! Try and use a thermometer throughout the experiment in order to accurately maintain your simulated body temperature. (If the temperature varies within, say, 5 degrees either side of your desired temperature, please make sure that your show this in your data, e.g. 98 degrees F +/- 5 degrees F.)

The addition of a hot water 'bath' to surround the Ziploc bag is a great idea - but please make sure that the water is not *too* hot. A little trial and error may be needed.

With regards to the particles remaining in your bag after a certain amount of time has passed - don't worry, this is to be expected! If you look at the packaging that the tablets come in, you will see the amount of "active ingredient", say 100 mg. If you were to weigh the entire tablet, you might find that it weighs 1 g. This means that only 10 % of the entire tablet is actually the active drug component! (1 gram = 1000 milligrams, 0.1 g is 10 % of 1 g) The other 90 % of the tablet weight is deliberately put there by the pharmaceutical manufacturer in order to allow the particular drug to get to where it needs to be in the human body before it dissolves (in addition to allowing for color-coding and labeling the tablet itself, etc.). All of these other ingredients do not need to get into the bloodstream like the drug needs to. As a result, this is what you are seeing remaining in the bag after the experiment should have been completed.

By the way, the 'pure water' that you are seeing surrounding the particles is not really pure water! This solution contains the active ingredient, as well as any other materials present in the tablet which have dissolved, such as sugars. It is only the undissolved or insoluble materials that you can see.

One way to measure the amount if insoluble material might be to first grind up one tablet and then to dry it out - this will remove any free water that may be present in the formulation. Carefully weigh what remains and write it down.

The next step is to take another tablet of the same type and to perform your experiment. Make sure that you record the volume of water that you are using to dissolve the tablet! After a particular amount of time, say, 1 hour (this is up to you, but it must be recorded), carefully filter the remaining particles and dry them. (Your teacher will be able to show you how to do this.) When these particles are dry, weigh them and compare the amount remaining to the original dry weight of the tablet. In theory, if the same volume of solvent (the water in the bag) is used, at the same temperature, over the same amount of time - the same amount of solids should remain (with some minor variations). Make sure that you record each result!

This experimental method should be repeated for each different type of drug you are examining. As with all experiments, try and make sure that you keep every variable the same except the one you are trying to study. This means that the same volume of solvent should be used in every run, at the same temperature, and agitated for the same length of time.

I know there will probably be other, more knowledgeable, people on this site who should be able to provide more information for you - but this should hopefully set your mind at ease! :D

Good luck, and please let us all know how your experiment goes!

Geoff.

Posted: Tue Nov 08, 2005 3:31 pm
by geoffbruton
Hi Joel,

In answer to your question, it really depends as to how you are defining "has lost its original shape." Although I have not performed this particular experiment myself, I would imagine that as the tablet begins to dissolve and come apart, small pieces of it will break away until you are eventually left with a solution of the drug and small parts of insoluble material.

I think as long as you start your timer as soon as the tablet is placed into the simulated stomach and agitate every minute (or however long your experimental method specifies), you can gauge at what point you believe the tablet has 'dissolved' as much as it is going to. Unfortunately, this is going to be somewhat of a judgement call - so try and make it as consistent as possible - and make sure you keep a good log of what you observe and at what time it happens. This last part is critical in research and should help you make a good comparison between your three test tablets. For example, you may find that after the first minute that Tablet 'A' has started to break up (half size? quarter size?), but that it takes another 5 minutes until the particles are evenly distributed throughout the simulated stomach. Tablet 'B', on the other hand, may take 5 minutes until it begins to 'dissolve', and then another 10 minutes until all of the particles are evenly distributed in the solution. Just be sure to record your observations and at what time they occur.

By the way, you are aware that the human stomach contains acid - and does not contain just pure water, don't you? This might complicate your project a little bit, but I would try and talk to your teacher about this. If time allows, you could always try and repeat the experiment with a small amount of dilute acid in the simulated stomach, in addition to the volume of water you used for the first set of experiments. You should then be able to report your findings as to how the acidity of the stomach contents affects the dissolving rate of the same tablets. Does that make any sense?

I didn't get a chance to commend your posting in an earlier email in which you stated that you were planning on running this experiment multiple times with each drug. That is an outstanding idea - and very important in any form of research! :D Since this experiment should not take a great deal of time to perform per run, I would suggest trying it out on each tablet and watching how they react. This may give you some good ideas as to when you can consider each tablet 'dissolved'.

Good luck - and if you need any more advice, please just let us know!
Geoff.

Posted: Tue Nov 08, 2005 7:42 pm
by phamlinh
Hi Joel,

With regards to dilute acid, I understand why your teacher would prefer that you not work with it for safety reasons. However, there are plenty of easily obtainable sources of acid. Lemon juice, vinegar, and coke would all work well. You may want to consider trying them as an additional condition. I'd be very interested in finding out whether the solubilities change in water versus an acidic condition.

Vinegar would be the best solution because it is just acetic acid. Lemon juice and coke both contain other ingredients that may affect your experiment.

Let me know how this sounds. Best of luck.

Linh

Posted: Wed Nov 09, 2005 9:59 am
by geoffbruton
Good morning, Joel & Linh,

Great to hear from you both. I absolutely agree with what Linh was suggesting with regards to using something like vinegar (dilute acetic acid) as a possible source of acid for your experiment. In fact, it occurred to me last night and I was going to say exactly the same thing this morning! :D With suitable precautions (don't get any of it in your eyes or inhale a lot of it, etc.), it would be interesting to see what effect, if any, it has on the solubility of your tablets. It's also very inexpensive - which is always a bonus! Maybe your teacher will agree to using something like that...

Well, I hope we have been able to steer you in the right direction. Your project sounds very interesting, so please be sure to post your results once you have finished your experiment.

Good luck!

Geoff.

Background reading

Posted: Fri Nov 11, 2005 6:38 pm
by deleted-71561
Joel

You've received some very good advice on how to carry out your project but I thought I'd make you aware that the experiments that you are carrying out are very important in drug development and are done by pharmaceutical companies every time a new drug formulation is developed.

The process is called Dissolution Testing and it's done with sophisticated equipment. The Food and Drug Administration (FDA, the part of the Federal Government that regulates medicines) even has specific guidelines on how dissolution testing should be done.

I know you don't have the equipment to carry out the testing like the pharmaceutical companies do but you might enjoy doing a search for "dissolution testing" on a search engine like Google and seeing what you come up with.

Best of Luck
Vijay