Ashlyn Kuhl
Age 14 | Desboro Ontario
Canada-Wide Science Fair 2019 Finalist
It is quite common for individuals to take over the counter pain medications for muscle aches, headaches, and discomfort, however not all over the counter medications are created equal. This investigation was designed to determine which over the counter medications dissolved the fastest in simulated gastric acid. This knowledge is important in determining which medication would most readily enter a person’s bloodstream in order to decrease distress for the individual. Research was conducted to better understand the marketing of common over the counter pain medications such as ibuprofen, acetaminophen, acetylsalicylic acid (ASA) and naproxen-sodium. Important variables between products included coatings and forms of each common drug. Building upon this background information, this experiment compared each variable (drug type, coating and form) in isolation.
INTRODUCTION
With the different coatings comes different purposes, the coatings tested in this experiment are film coatings, sugar coatings, rapid release gel caplets, liquid gels, and enteric coated medications. Film coatings are very thin film, coating the medicine. This is most commonly used for coating ASA and naproxen-sodium. They are known for being easier to swallow than other products, and they are compact. Sugar coatings are made of sugar and wax, and usually resemble candy. They are most commonly used for ibuprofen and acetaminophen. Sugar coatings are designed to dissolve quickly, as well as slide down easily due to the wax based coating. Rapid release gel caps are a mix of a film coating and liquid gel. The medication is coated in a liquid capsule, and a film. This sort of coating is very streamlined, easier to swallow and is designed to dissolve at rapid speeds. Liquid gels are liquid, therefore when swallowed they are designed to dissolve very while being easy to swallow. Liquid gel coatings are usually found on ibuprofen. Enteric coated medications use a coating similar to a film, however they are designed to dissolve in the intestines rather than the stomach. This is desirable for people with stomach ulcers and other gastric health conditions as it prevents harm to the stomach by dissolving in the intestines (Wright, D. Different Coatings-Swallowing Difficulties). Gastric acid is found in the stomach and its main purpose is to help break down food and medications that enter the digestive system. Therefore stomach/gastric acid is what breaks down your medication. Gastric acid tends to have a pH. of 1, 1.5, or 2 (Le, J. Drug Absorption- Clinical Pharmacology). Hydrochloric acid can be used to simulate stomach acid due to the similar pH. levels. It was very important to conduct this experiment with as little variables as possible, so creating simulated stomach acid with the correct heat and pH. level was essential. The active ingredients were also researched to determine their most probable reaction(s) with stomach acid. The purpose of this investigation was to determine which of 12 common over the counter pain medications would dissolve the fastest in simulated stomach acid.
HYPOTHESIS
It was believed that the selection of medications with a film coating such as Aspirin will dissolve the fastest in the simulated stomach acid, followed by the quick release gel medications, liquid gels, sugar coated medications, and finally the enteric coated medication.
MATERIALS
When conducting this experiment, one pair of latex gloves, and safety glasses were required safety equipment as chemicals were involved. Required glassware for this experiment included 15 100 mL beakers, a 10 mL pipette, two 220 mL syringes, and a 1L glass flask. Chemical reagents consisted of 10.17 molar Muriatic Acid (hydrochloric acid, HCl), 4L of distilled water, commercially available calcium carbonate (Tums), and one can (approx. 330 mL) each of 7-Up, Schwepps Ginger Ale, and grapefruit juice. Additionally, one bottle (16 or 32 tablets in each) of the medications being tested were required, including Aspirin Extra Strength Tablets, Aleve Extra Strength Caplets, Equate Extra Strength Liquid Gel Tablets, Tylenol Extra Strength Gel Caps, Equate Extra Strength Liquid Capsules, Advil Extra Strength Liqui-Gels, Advil Extra Strength Caplets, Tylenol Extra Strength Tablets, Equate Extra Strength Tablets, Life Brand Extra Strength Tablets, Aspirin Stomach Guard, and Entrophen. Other miscellaneous materials required for the experiment included stop watches, pH testing strips, liquid thermometer and Thermolyne hot plate. Lined paper and a pen were also used to record observations.
PROCEDURE
All lab safety rules and regulations for working with chemicals in a laboratory setting were followed, which included wearing closed toe shoes, gloves, goggles, and having long hair tied back.
The HCL was prepared at the given pH. Sample equation as follows:
Mdesired X Volumedesired = Mstock X Volumestock (note: HCl and H are 1:1 in H+)
When making a 1 L solution with a desired pH 1, the [H+] concentration will be 10-1mol/L or 0.1 mol/L. The acid used had a molarity of 10.17 mol/L.
(0.1 X 1 L)/10.17 = volume required in litres 0.0098 L = 9.8 ml
In the first part of the experiment, 1 L of distilled water was poured into the 1L flask and heated on the Thermolyne hot plate on the lowest setting until the water reached a temperature of 37 degrees Celsius, using the liquid thermometer to monitor changes. The hot distilled water was then mixed with the quantities of HCl determined through the formula above in a glass flask to make 1 L of simulated gastric acid. The pH was checked using pH strips to ensure that the HCL was consistent and at the desired pH. The HCl was mixed into the water very carefully by shaking and stirring motions until blended well in the 1L flask for 1-2 minutes. 25 ml of the simulated stomach acid was poured into each 100ml beaker, one for each medication, using the pipette and syringe. After dropping one tablet of each medication into their respective beakers, the timer was started and observations began to be recorded. This procedure was repeated three times per medication, per pH level.
In subsequent iterations of the experiment, 20 mL of soda or juice was added after mixing the simulated stomach acid. This was to simulate the effect of someone swallowing the medication with 7-Up, Grapefruit Juice, or Ginger Ale. This was included as through a conducted survey it was determined that some people prefer to consume medication with those liquids, despite pharmacists recommend not to consume medication with those beverages. The medication of each coating type that dissolved the fastest on average was tested once in each beverage with HCl and once in each beverage alone to simulate when the medication travels down a patient’s throat. Another trial was conducted to observe the effect of sodium carbonate (Tums) on stomach acid, in which one Tums tablet was allowed to dissolve in the simulated stomach acid, after which the pH of the acid was tested. In the Tums trial, none of the tested medications were included.
All wastes produced in this experiment were disposed of responsibly.
RESULTS AND OBSERVATIONS
While conducting this experiment it was observed that the majority of medications more readily dissolved fully in lower pH levels, due to the higher acidity, although there was slight variation in the times. Entrophen did not fully dissolve in simulated stomach acid at any of the pH levels, although it did fizz a bit. Independently all medications dissolved quite consistently, excluding the Advil Extra Strength Liquid Gels and the Equate Extra Strength Liquid Gels, which had much larger ranges than the other medications.
For the trials testing the effect of the different beverages and the tums, only the fastest dissolving medication from each coating type was tested. It was observed that medications in film or sugar coating were broken down quicker by the presence of pop, though it was not large enough to warrant taking medication with pop instead. Gel caps dissolved around the same point of time in both trials with pop and in isolated HCl trials. Liquid gels took longer to dissolve in the pop and juice than in the isolated HCl trials. The results from each standard procedure (excluding trials in which pop or juice were added) are presented in Figure 1.
Figure 1. Average time taken for medications to begin to dissolve (above) and to dissolve completely (below).
DISCUSSION
Medications with a film coating such as Aspirin Extra Strength Tablets (ASA), Aspirin Stomach Guard (ASA) and Aleve Extra Strength Caplets (naproxen-sodium) were predicted to dissolve readily in simulated stomach acid as they have a very thin film coating. When the coating came intp contact with the highly acidic stomach acid it was believed they would dissolve quite quickly. The Aspirin Extra Strength and Aspirin Stomach Guard tablets did dissolve readily in simulated stomach acid, with dissolution completion times of 0.79 and 11.14 minutes, respectively. However, the Aleve Extra Strength Caplets took an unexpected 39.40 minutes to dissolve completely, the longest dissolution time recorded. This may be explained due to the longer lasting medication. Aleve is made to last 12 hours while the other medications were designed to last 4-6 hours. As it is made to last longer, it would dissolve slower in order to stay in the system longer. Gel capsules contain liquid medication that is dissolved quite quickly by the stomach wall. This type of medication includes Equate Extra Strength Liquid Gel Tablets (acetaminophen) which possesses an open section in the middle that leaves medication exposed and easily distributable to the bloodstream. The name brand equivalent to this is Tylenol Extra Strength Gel Caps, which have a very similar design, including vent style openings in the middle which medication exposed. Of the three gel capsule medications tested, Tylenol Extra Strength Gel Caps had the fastest time to complete dissolution, starting at 0.20 minutes and completing at 2.62 minutes. The Equate Extra Strength Liquid Capsules and Advil Extra Strength Liqui-Gels had similar dissolution times of 0.70 to start and 24.96 completely, and 3.28 to start and 25.36 completely, however both took much longer to dissolve than Tylenol Extra Strength Gel Caps and their generic counterpart. This may be due to the difference in active ingredients, as the Equate Extra Strength Capsules and Advil Extra Strength Liqui-Gels are both ibuprofen, while the Tylenol product is acetaminophen. Alternatively, the difference in dissolution times could be due to structural dissimilarities. While all of these medications have very similar coatings and contain a liquid active ingredient, the ibuprofen products did not feature vent style openings to better expose the medication to stomach acid. The next several medications to dissolve may be the sugar and wax coated medications, as they have a dense, candied coating. This grouping includes Advil Extra Strength Caplets (ibuprofen), starting at 0.28 minutes and completing at 2.24 minutes. Tylenol Extra Strength Tablets (acetaminophen), starting at 0.75 minutes and completing at 7.54 minutes. Equate Extra Strength Tablets (acetaminophen) started dissolving at 0.73 and completing at 5.05 minutes. Life Brand Extra Strength Tablets (acetaminophen) started dissolving at 1.48 minutes and completely dissolved at 8.22 minutes. These medications dissolved slower than the film coated medications and rapid release gel caps but significantly faster than the gel caps. The Advil caplets were always much faster than the other caplets. This could be due to the different medications, as Advil is ibuprofen and the others were all acetaminophen.
The medication to take the longest to dissolve of the dozen medications tested is Entrophen (ASA) as it has an enteric coating, produced to withstand gastric acid and dissolve in the intestines, in order to protect the stomach from the medication. Entrophen never fully dissolved in the stomach acid, therefore it is truly enteric coated. It would start to dissolve but it never fully dissolved.
It was observed that the lower the pH in the stomach acid, the faster the medications dissolve, and the juice and pop can cause medications to dissolve faster due to the added acidity and carbonation, though it was observed that it did not make a significant difference in time, so it is not worth taking your medication with pop or juice, as it could cause harm (Conversation with Dinesh Shah, April 12th 2019).
Major manufacturers like Advil and Tylenol tend to use several different coatings, and the reasoning behind this is serving the customers the best they can. For people with difficulty swallowing, there are coatings designed to go down easier. For people with stomach conditions, there are coatings to dissolve in the intestines instead. This is all formulated to help people with various conditions get the relief they need, in the safest and easiest way. This experiment has demonstrated that changing the coating and form of a medication can change its rate of dissolution in the stomach, further illustrating the importance of having various product types on the market.
This experiment also included variables to account for naturally occurring differences between patients’ stomach acid and the conditions under which they take the medications. Creating the most accurate simulated gastric acid to represent everyone was very important so that the results were applicable to people if all sorts. Some people have a very low pH. level of stomach acid such as 1, where others have stomach acid at a pH. of 2. Completing trials at several pH. levels was very important to give the most applicable overall results to the consumer. The variables of pop were included because when a convenient random sample was conducted, most people reported to take their medication with a liquid other than water, such as ginger ale and grapefruit juice. Pharmacists do not recommend taking medication with those liquids as it may cause your medication to dissolve dangerously fast or too slow (Conversation with Dinesh Shah, April 12th 2019). Since people do however consume medication with these liquids it was important to include as an educational opportunity to investigate how much of an affect varying stomach pH could have on medication uptake.
CONCLUSIONS
This investigation has concluded that medications with a gel cap coating, with venting, and powder medication (i.e Equate Extra Strength Liquid Gel Tablets and Tylenol Rapid Release Gels) dissolve quite fast in all pH levels tested of simulated stomach acid, as well as medications with a film coating such as Aspirin Tablets, and Aspirin Stomach Guard. Liquid Capsules tend to take a significant amount of time to dissolve, and sugar-coated medications tend to be the middle ground. This information is important because the information available to consumers is generally limited to how companies advertise. Gel caps can be advertised as dissolving in minutes when that is not necessarily accurate. This information is also important for making new medications because the coating is an important component in drug formulation. For some applications, having a coating that dissolves quickly is a necessity, while for other applications it could be very undesirable. However, for daily use to treat minor aches and pains what it really comes down to is that every minute matters. In these situations, consumers do not want to wait for relief.
ACKNOWLEDGEMENTS:
The following individuals should be recognized for their suggestions and help with this investigation: Dinesh Shah, Heather Christie, Krista Kuhl, Dustin Behm, Patti Jo and Brad Lacey.
REFERENCES AND BIBLIOGRAPHY
Conversation with Dinesh Shah, April 12th, 2019.
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ASHLYN KUHL
My name is Ashlyn Kuhl and I am a grade nine student at St. Mary’s High School in Owen Sound. I am 14 and live near Keady, Ontario. Science has always been an interest of mine, especially the health and chemistry fields. When I’m not in class I can be found playing piano or ukulele, singing, acting in local productions, or dancing. I have competed at the regional science fair level five times, and have earned several medals at that level. In 2019 I made Team Bluewater for Canada Wide Science Fair in Fredericton as a finalist. I hope to pursues career in health care or chemistry.