April 28, 2006
Group Number 4A
Section 101
______
Testing Effectiveness of Common Antacids: Titration of Commercial Buffers
______
Danielle Friedman
David Hwang
Ankur Patel
Victoria Tsai
Background
This proposal expands on Experiment 2, “Acid-Base Chemistry: Biological Buffers.” Resistance of partly neutralized weak acids or bases present in aqueous solution to change in pH is known as “buffering.” In various systems of the body that require constant pH, buffers are used to control acidic or basic conditions and keep enzymes and organs working at their pH optimum. Antacids are over-the-counter drugs in tablet or liquid form that dissociate at the pH of the stomach and react with acids to neutralize excess acid and act as a buffer. Most commercial antacids contain calcium carbonate, magnesium hydroxide, or a combination of the two. By observing the activity of different antacids in an experimental environment similar to the stomach, it can be determined which one functions best.
As in Experiment 2, this experiment titrates a weak base (in this case, the active ingredient of different types of antacids) against a strong acid (HCl, to model the function of the antacid in the stomach). Both magnesium hydroxide (Mg(OH)2) and calcium carbonate (CaCO3) should exhibit predictable behavior similar to that observed in part 2 of Experiment 2, Standardization of Acid Solution with a Primary Standard, since all the reactions involve the titration of the same strong acid (HCl) with various weak bases. The pure form of the active ingredient is used to simplify the procedure and reduce uncertainty.
The curves for both titrants should be similar in shape to the curve for Na2CO3 observed in Experiment 2, however the Mg(OH)2 titration curve will only exhibit one pKa. The CaCO3 curve should be most similar to the curve in Experiment 2 (Figure A, Appendix). From the differentiation of this curve, pKa values of the acid can be determined as an indication of experimental accuracy and the buffer index can be calculated as the measure of antacid performance (Figure B, Appendix). The calculations of pKa and buffer index will be performed as they were in Experiment 2 and found to be 2.042, 6.761, and 11.542, and 0.00828 ± 0.0005 (mean ± SD), respectively. While the respective curves should be similar to those found in Experiment 2, the buffer indices should vary for Mg(OH)2 and CaCO3. Because the same basic procedure is being followed in the proposed experiment, equipment and materials will differ only in the chemicals used. The proposal is grounded in an experiment that is proven to be able to be used to determine the sought quantities, which in turn are accepted indicators of buffering ability.
Objective and Aim
The buffer index, pKa, and amount of acid neutralized by the active ingredients of two antacids, calcium carbonate and magnesium hydroxide, will be calculated from titration curves and compared to determine which is the most effective buffer under physiological conditions. The most effective buffer is defined by highest buffer index, pKa most similar to the pH at physiological conditions, and highest amount of acid neutralized.
Proposed Methods
This experiment seeks to compare the buffering capabilities of two common antacids, Mg(OH)2 and CaCO3, in their pure form. Analysis will compare the effectiveness of the buffers in the acids in the stomach, empirically comparing the buffering index, the pKa, and the amount of acid neutralized per weight. As this experiment only seeks to analyze the effectiveness in the stomach, the only effective buffering ranges considered will be the ones with pH’s within the range of the stomach. Gastric juice ranges from pH 1 to pH 3, so the effective buffering ranges chosen will be within pH of 1 and 3. The theoretically best antacid would have the largest buffer index, the effective buffering pH within 1 and 3, and the highest amount of acid neutralized per weight.
On the titration curves of the bases, the effective buffering range is defined graphically as the flattest portions of the curve. This correlates to the area with the lowest first derivatives, which consequently relates to the area with the highest buffer index, as buffer index is defined as d[A]/d{pH], where A is the strong acid used in the titration.
Buffer index will be calculated from the linear portion of the effective buffer range on the titration curves. Effective buffering pH will be measured as the pKa of the effective buffering range, which is defined as the inflection point located within the effective buffering range.
The amount of acid neutralized will be calculated by moles of acid added to make the titration solution move from pH 3 to pH 1, divided by the weight of base used, as the neutralization varies with the amount of base. This way, the amount of acid neutralization can be used in relative comparison between the two types of antacids.
Titrations will follow the weak base/strong acid protocol in Experiment 2.
Proposed Protocol
1. Prepare antacid solutions by adding 1.500g of Mg(OH)2 and CaCO3 to separate beakers with 100 mL of deionized H2O.
2. Prepare 300mL of 1.0M solution of HCl.
3. Place two to three drops of the pH indicator thymol blue in each solution.
4. Calibrate pH meter according to manual.
5. Titrate each solution with 1.0M HCl, adding .25mL HCl between pH measurements, recording points throughout the titration.
6. Repeat titrations twice more for each solution, recalibrating between trials
7. Graph titration curves from data.
8. Analyze and calculate average buffer index, pKa values, and amount of acid neutralized by graphical analysis of curves as defined above.
Anticipated Results
The curves obtained from the titrations will be used to compare the effectiveness of CaCO3 and Mg(OH)2 as buffers in antacids. Figure 1 below is an example of a generic titration curve.
As indicated on the curve in Figure 1, the effective buffer range corresponds to the flat portions of the curve. The inflection points of the titration curve correspond to the pKa.
The following are the chemical reactions of CaCO3 and Mg(OH)2 with HCl:
(1) CaCO3 + 2HCl → CaCl2 + H2CO3
(a) CO32- + H+ → HCO3-
(b) HCO3- + H+ → CO2 + H2O
(2) Mg(OH)2 + 2HCl → MgCl2 + 2H2O
The titration curve of CaCO3 should have 2 pKa values due to CO3 having a charge of -2. The titration curve of Mg(OH)2 should have 1 pKa value due to OH having a charge of -1. Table 1 shows accepted literature pKa values of the active ingredients being tested.
Table 1. pKa Values
Active Ingredient / pKa ValuesCaCO3 / 10.3, 6.3
Mg(OH)2 / 13.0
From the titration curves, the buffer indexes should be calculated and compared. It is likely that neither CaCO3 or Mg(OH)2 will a good buffer, but instead, just act as acid neutralizers. The data should show that Mg(OH)2 is a more effective active ingredient for antacids (p<0.05) than CaCO3. Since the two active ingredients are being compared based on mass (since doses based on mass) and Mg(OH)2 is lighter than CaCO3, Mg(OH)2 should have greater neutralizing capability.
Potential Pitfalls & Alternative Methods/Analysis:
The following is a list of potential pitfalls that could occur during the titrations:
1. If the titration does not produce a smooth curve and regions of the curve are missing, too much HCl was added between measurements.
2. If the samples are not pure, the titration curves will not reflect the true behavior of the antacids. Be sure to take extra care in measuring samples and transferring from one location to another.
3. If the molarities of the solutions are not accurate, then the buffer index will be an inaccurate representation of the effectiveness. However, the pH range of the flat portions of the curve would not be affected by variability in molarity and could be used as an alternative method of analysis. If the pH range of these flat portions correspond to the pH of the stomach (1-3), then the antacid is effective.
Equipment
Major Equipment:
· pH meter with combination glass-silver/silver chloride electrode and holder
The pH meter will be necessary to monitor the titration and assess the buffering capacity of the two antacids. The obtained pH data will be used to graph the titration curve.
Lab Equipment:
· Magnetic stirrer and stirrer bar
· Balance
· Two 50 mL burettes and burette stand
The above mentioned lab equipment will be necessary in carrying out the procedures of the experiment. The balance will be used to measure out the specific amounts of chemicals and the magnetic stirrer and burettes will be used in the titration process.
Supplies:
· Calcium Carbonate (CaCO3)
· Magnesium Hydroxide (Mg(OH)2
· Hydrogen Chloride (HCl)
· Indicator: Thymol Blue
The supplies include the two active ingredients being tested (calcium carbonate and magnesium hydroxide) and hydrogen chloride which will be used to titrate them. In addition, the thymol blue indicator will be used indicate the endpoint of the titration.
Newly Purchased Equipment:
The chemicals used in this experiment, calcium carbonate, magnesium hydroxide, hydrogen chloride, and thymol blue indicator, will need to be purchased. No new equipment will be necessary for purchase - all equipment that is needed for this experiment is already present in the lab.
Budget
The supplies that will need to be purchased are the two active ingredients in antacids, hydrogen chloride which will be used to titrate the two active ingredients, and thymol blue indicator to monitor the endpoint of the titration.
In order to complete the three trials of each titration, a group will need the following amounts of each of the chemicals:
- Calcium Carbonate (CaCO3):
o For each titration, 1.50g of CaCO3 will be used. Therefore, no more than 5.00g per group is necessary.
- Magnesium Hydroxide (Mg(OH)2):
o For each titration, 1.50g of Mg(OH)2 will be used. Therefore, no more than 5.00g per group is necessary.
- Hydrochloric Acid (HCl):
o For each titration, no more than 50mL of 1M HCl will be used. In order to create a 1M solution, 1.8g of HCl will be added to 50mL of deionized water. Since each group performs six titrations, no more than 300mL will be needed. Therefore, no more than 11.0g of HCl will be needed per group.
Thus, for 20 groups to complete this experiment the following amounts of each chemical, with their respective costs, are needed:
Item / Supplier / Price / Quantity / SubtotalCalcium Carbonate (CaCO3) 500g / Sigma-Aldrich (CAS Number: 471-34-1) / $91.50 / 1 / $91.50
Magnesium Hydroxide (Mg(OH)2) 250g / Sigma-Aldrich (CAS Number: 471-34-1) / $41.80 / 1 / $41.80
Hydrochloric Acid (HCl) 227g / Sigma-Aldrich (CAS Number: 7647-01-0) / $218.50 / 1 / $218.50
Thymol Blue Indicator 25g / Sigma-Aldrich (CAS Number 76-61-9) / $72.00 / 1 / $72.00
Total / $423.80
Appendix
Figure A. Titration curve of sodium carbonate with hydrochloric acid, as measured in Experiment 2. Two trials were performed with acid added and pH measured at 0.5mL intervals.
Trial 1 Titration Curve for the Titration of Sodium Bicarbonate (weak base) with Hydrochloric Acid (strong acid). The value for the end point of the titration is indicated as a dark blue dot. The two literature values for pKa values are also marked as points on the graph.Figure B. Titration curve of phosphoric acid with sodium hydroxide and subsequent graph used to calculate buffer index.
Trial 2 Titration of Phosphoric Acid (weak acid) with Sodium Hydroxide (Strong Base). The estimated pKa values and the estimated isoelectric point (pI) are marked on the graphFigure 6: The dB/dpH vs. pH graph for Trial 2 used for determining the buffer index value.