Introduction: Acetylsalicylic acid, acetaminophen, and ibuprofen are all active ingredients for pain relievers. However, these pain relievers are not purely composed from one of these three active ingredients. Analgesics (pain-relievers) also contain starch or other inert substances to keep the tablet from falling apart and make them large enough to handle. Also, many of these drugs have coating so that the tablet is easier to swallow and doesn’t taste bitter. In this experiment we will learn microscale level lap techniques such as vacuum filtration, column chromatography, and centrifugation to extract the active ingredient from tablets.
Separation and Purification Scheme:
- Analgesic with Binder Add methanol (CH3OH) dissolve analgesic
- Analgesic in solution with binder
- Centrifuge +filtersome binder
- Analgesic in solution with binder
- Alumina columnremaining binder
- Analgesic in solution with methanol
- Evaporate most CH3OH (methanol)
- Analgesic and some methanol
- Remaining CH3OH (methanol)
- Ice bath
- Analgesic crystal and methanol
- Vacuum filtration
- Pure analgesic crystal
- Use one tablet of aspirin, acetaminophen, or ibuprofen.
- Crush tablet using a mortar and pestle. Makes sure all the tablet’s coating is removed by using forceps.
- Add crushed tablet, without coating material, into a 3-ml council vial
- Add 2ml of methanol to the 3-ml conical vial using a glass pipet
- Cap the vial and shake it thoroughly, making sure the solution is well mixed. Allow for a release in pressure build up by opening the cap.
- Wait for the larger un-dissolved powder portions have settled in the vial (about 5 minutes)
- Use a pipet to transfer the remaining liquid into a centrifuge tube
- Add another 2ml of methanol to the vial and repeat steps 5-7. Add this liquid to the same centrifuge tube.
- Place the centrifuge tube opposite a tube with the same weight in the centrifuge for 2-3 minutes. Repeat (longer and faster) if supernatant liquid is not clear
- Transfer supernatant liquid to a test tube with a pipet
- Insert a small cotton ball to the bottom of a pipet. Push the cotton down with a stirring rod.
- Add 0. 5 g alumina and tap the pipet to pack
- Clamp the pipet so that it is vertical above a 5ml conical vial
- Add 2ml of methanol and allow it to drain until it is equal with the top of the alumina. Make sure to add more methanol to prevent the top of the alumina from running dry.
- Add the solution from the test tube
- After the solution has drained, add another 1mL of methanol to the filtration system.
Evaporation of Solvent Note: evaporation must be done in 10-15minutes if handling aspirin
- Use a pipet to transfer the liquid into small beaker
- Place the beaker in a 50°C water bath
- Use a stream of dry air or nitrogen to evaporate faster
- Evaporate solvent until there is less than 0. 5 ml left
- Remove beaker from bath when evaporation is complete and allow vial to cool to room temperature
- If liquid remains place the beaker in an ice bath for 10-15 minutes. Scrape sides of vial with a micro-spatula for faster crystallization
- Use a micro-spatula to break up the solid as much as possible
- Set up a vacuum filtration with a filter flask (50 ml) that is connected by a heavy walled rubber tube to the vacuum. Make sure to clamp and stabilize the filter flask.
- Seal a Hirsch funnel to the filter flask by some Gooch tubing
- Fit a fritted polyethylene disk into the funnel with a filter paper of the same size
- Moisten the filter paper with drops of methanol and turn the vacuum on for 5-10 minutes
- Scrape dried crystal onto a previously weighed tarred watch glass and break up large pieces of solid. Allow to air dry. (Note: Ibuprofen is slightly sticky even when dry)
- Weigh watch glass now and determine weight of active ingredient
- Calculate weight % recovery using weight from label
- Crush crystals into powder with a stirring rod and use a melting point device to determine the melting point of your active ingredient.
- Record the melting point. Watch for sweating or shrinkage
- Place product in a small vial and label it for the professor.
Observation: My analgesic drug was Ibuprofen which as a long white pile. When crushed it turned into a fine white powder. After methanol was added the solution turned cloudy white with some precipitate at the bottom. It was still cloudy white after waiting for 15 minutes so it was sent to the centrifuge. The centrifuge made the solution clear with precipitate in the bottom. After column chromatography we ended up with a clear solution also.
After the water bath there was semi cloudy solution that was less than 0. 5ml. The ice bath pared along with scrapping the beaker with a stirring rod left turned the solution into a clumpy white powder. It was still a clumpy white powder after vacuum filtration. The melting point, which was when the powder started to “sweat” and bubble under the microscope, was discovered to be at 70°C for Ibuprofen. Calculations: Percent weight recovery= (actual amount/ theoretical amount ) x100 61%=368mg/600mg 61% percent weight recovery
Discussion and Conclusion: The purpose of this lab was to extract the active ingredient from the tablet we were given. I was given one tablet of Ibuprofen that had a theoretical weight recovery of 600 mg. My actual recovery was 365 mg of active ingredient with a 61% recovery. My percent recovery is relatively high compared to others who did the same experiment, however, solution spillage and loss of active ingredient during vial transfers could account for a less than perfect experiment. Also, we have to keep in mind that chemistry experiments never have a 100% yield in actuality.
The melting point that I got for Ibuprofen was 70°C, which is 5°-7°C lower than expected. Since Ibuprofen is suppose to have a slightly lower melting point then the given melting point, my measurements were pretty accurate—suggesting that I had a very pure sample of active ingredient. Chemists would use the techniques learned in this experiment to help identify unknown drugs by determining their melting points.
Post-Lab Questions: Question 1, page 74. The percent recovery was less than 100% (61%) mainly because I had several spillages of my solution both before and after centrifugation. Active ingredient would have been lost in both spillages and also during the transferring of solution/power between vials, pipets, and beakers. Although I did the best I could I couldn’t manage to scrape off all of the powder from the beaker in the ice bath which left a lot of active ingredient behind. Also, if any binding substances or methanol was still left in the final product it would have made the percent recovery larger than it actually was. Also, all chemistry experiments are expected to have a less than perfect yield.