Teacher and technician notes TC3.14 Lesson reference: C3.14 Making medicines Book links: Page 116 Specification links: C3g Making medicines Equipment required per student/group: Student activity AC3.14.1 Making medicines Set of laminated cards Student activity AC3.14.2 Testing medicines Thin layer chromatograph demonstration (optional) Thin layer chromatography plate, about 8 cm × 5 cm Three watch glasses Two thin capillary tubes Sample of pure aspirin (2-ethanoylhydroxybenzoic acid) (harmful) Sample of aspirin contaminated with either salicylic acid (harmful) or benzoic acid (harmful) Ethanol (highly flammable, harmful) 3 20 cm chromatography solvent Chromatography beaker or jam jar A few crystals of iodine (harmful) Notes on equipment: These cards can be found below. They need to be prepared in advance of the lesson. The chromatography plate needs to be pre-dried and able to fit into the chromatography beaker beaker. Label the pure aspirin ‘A’ and the contaminated aspririn ‘B’. Industrial denatured alcohol (IDA) will do. Chromatography solvent can be made by combining cyclohexane (highly flammable, harmful) Small beaker Access to a fume cupboard Melting point demonstration (optional) ethyl ethanoate (highly flammable, irritant) Melting point apparatus Two melting point tubes Two spatulas ethanoic acid (corrosive) in the ratio 200:100:1 Fundamental Scientific Processes: Explain how the application of science and technology depends on economic, social and cultural factors (L, S, H). Health and Safety notes: Wear eye protection for the demonstrations. Work in a well ventilated laboratory. Starting off This is potentially quite a time-consuming part of the specification. Some important aspects of the drug testing process are dealt with in Homework task (HC3.14.1) Making medicines. Make sure that suitable feedback is given on this task to ensure that all students are fully prepared for exam questions which cover this section of the specification Practical activities have been checked for health and safety advice by CLEAPSS. All users will need to review the risk assessment information and may need to adapt it to local circumstances. © Oxford University Press 2010 This document may have been altered from the original. 1 Students will probably use the ideas they have developed about industrial processes in Module C1 Carbon chemistry and other recent lessons. They will probably raise issues like energy costs and raw materials costs. Emphasise that the cost of drugs is affected by these factors but there are other factors which are more significant. Main ideas Student activity AC3.14.1 Making medicines This card-sorting activity follows on from Presentation (IC3.14.3) Making medicines in exploring the steps involved in drug development. The cards should ideally be laminated in advance of the lesson. They can be stored in envelopes or self-sealing plastic bags for re-use. ✄ Stage What happens in this stage Why this stage is expensive development the drug is given to a group of healthy volunteers to test that it is safe legal approval takes time, it may be difficult to persuade doctors to prescribe the drug phase 2 and 3 trials compounds are identified which may have a beneficial effect on a disease the volunteers need to be paid and closely supervised by doctors approval and marketing a way of making the compound from raw materials is developed it may take several years before it is clear whether the drug is effective discovery research the product gets legal approval and doctors are informed about the drug the raw materials may be costly, rare or difficult to make into the new compound phase 1 trials the drug is given to patients suffering from the disease millions of compounds may need to be tested, taking many years Student activity AC3.14.2 Testing medicines Students will have done some paper chromatography before. Point out that thin layer chromatography is similar to paper chromatography but uses a thin layer of silica painted onto a plastic plate. The principle is very similar. As solvent rises up the plate, different substances move at different speeds. If you choose to demonstrate the thin layer chromatography, it will take around 35 minutes. However, about 20 minutes of this is spent waiting for the solvent to rise up the paper. You can use this time to discuss melting point measurements or ask students to complete one of the Student activity sheets. Explain the principles of melting point measurement to the students. Practical activities have been checked for health and safety advice by CLEAPSS. All users will need to review the risk assessment information and may need to adapt it to local circumstances. © Oxford University Press 2010 This document may have been altered from the original. 2 If a melting point apparatus is available, it could be shown to the students. However, the action of taking a melting point using it is not very visual and unlikely to be very engaging. You may want to show how samples are prepared for the melting point apparatus by placing a few crystals in a melting point tube. If time allows, students could analyse the chlorophyll extracts they obtained in Lesson (C3.13) Batch or continuous? although this is not required by the specification. Full experimental details can be found by going to the Science & Plants for Schools website at www.saps.org.uk and searching for ‘chlorophyll chromatography’. Thin layer chromatograph demonstration (optional) 1 Handle the TLC plate by the edges only and draw a thin pencil line 1 cm from the bottom of the plate. This is the baseline. 2 Take a few crystals of each of the aspirin samples and dissolve them in a minimum volume of ethanol on a watch glass. To do this, try a few drops, then add more ethanol if required. 3 Using capillary tubes, place small spots of your aspirin samples on the baseline. Ensure the three spots are well spaced out along the baseline but are not too close to the side edges of the TLC plate. Label them A and B in pencil. To achieve small, concentrated spots, apply a small quantity of the solution then let them dry before adding a second spot on top of the first. Try not to let the diameter of the spots exceed 2 mm. 4 Working in a fume cupboard, pour some of the chromatography solvent into the beaker to a depth of no more than 5 mm. 5 Place the chromatography plate in the beaker, making sure that the solvent level is below the baseline. 6 Cover the beaker with the spare watch glass Leave the solvent to rise up the TLC plate. This will take about 15–25 minutes. 7 When the solvent has nearly reached the top of the plate, take the chromatogram out of the beaker. Place the plate in a fume cupboard and allow the solvent to evaporate. 8 The positions of the spots on the plate can be located by examining them under UV light. However, this will be difficult to do as part of a demonstration. Instead, place the plate in the small beaker containing a few crystals of iodine. Cover the beaker with a watch glass. The spots, which were probably just visible before, should show up clearly as dark brown. Plenary The drag-and-drop will give a brief summary of the main steps. If time allows, there could be more discussion about the nature of the tests and trials, especially the design of the phase III trials, leading into the homework. The extraction of plant chemicals only needs to be covered at a very descriptive level. Practical activities have been checked for health and safety advice by CLEAPSS. All users will need to review the risk assessment information and may need to adapt it to local circumstances. © Oxford University Press 2010 This document may have been altered from the original. 3 Answers Student activity AC3.14.1 Making medicines Stage What happens in this stage Why this stage is expensive discovery research compounds are identified which may have a beneficial effect on a disease millions of compounds may need to be tested, taking many years development a way of making the compound from raw materials is developed the raw materials may be costly, rare or difficult to make into the new compound phase 1 trials the drug is given to a group of healthy volunteers to test that it is safe the volunteers need to be paid and closely supervised by doctors phase 2 and 3 trials the drug is given to patients suffering from the disease it may take several years before it is clear whether the drug is effective approval and marketing the product gets legal approval and doctors are informed about the drug legal approval takes time, it may be difficult to persuade doctors to prescribe the drug Student activity AC3.14.2 Testing medicines Investigating A Sample A is the most pure. It has the melting point which is closest to the data book value B Sample A is the most pure. It produces only one spot so it contains only one substance Spreading the word A Both melting point tests and thin layer chromatography tests are done on samples of drugs because doing two tests increases the reliability of the tests. B The boiling point of oil of wintergreen should be measured together with a TLC test. C i Sample B was impure aspirin. ii Sample A does not appear to contain any aspirin. Practical activities have been checked for health and safety advice by CLEAPSS. All users will need to review the risk assessment information and may need to adapt it to local circumstances. © Oxford University Press 2010 This document may have been altered from the original. 4