Acid-Base Equilibria - Drug pH Calculations

Acid-Base Equilibria - ILO's

• Calculate the pH scale of hydrogen ion concentration
• Evaluate pH values of salts of simple weak acidic and basic drugs
• Use the Henderson-Hasselbalch equation to estimate the pH of a buffer solution and find the equilibrium pH in acid-base reactions of weak drugs
• Recognize the concept of buffering capacity as a quantitative measure of resistance to pH change upon the addition of H+ or OH- ions
• Explain polyprotic acidic and basic drugs and their salts
• Calculate the pH of the solution of a polyprotic acidic and basic drugs
• Construct fractions of polyprotic species as a function of pH

Acidic/Basic Drugs - pKa Values

• Acetyl salicylic acid (Acid) - pKa 3.49
• Benzyl penicillin (Acid) - pKa 2.76
• Ethosunamide (Acid) - pKa 9.3
• Chlorpropamide (Acid) - pKa 4.8
• Sulfadrazine (Acid) - pKa 6.48
• Dephenghydantoin (Acid) - pKa 8.3
• Atropine (Base) - pKa 9.65
• Amphetamine (Base) - pKa 9.8
• Lignocaine (Base) - pKa 7.9
• Procaine (Base) - pKa 8.8
• Tetracycline (Base) - pKa 3.3, 7.8, 9.7

Acid-Base Theories

• Arrhenius Theory:
  • Acid: substance that ionizes in water to produce H+ ions increasing H3O+ concentration
  • Base: substance that ionizes in water to produce OH- ions
  • Limitation: doesn't explain acids/bases in non-aqueous solutions
• Brønsted-Lowry Theory:
  • Acid: proton donor
  • Base: proton acceptor
  • Conjugate acid-base pairs involve the transfer of a proton
  • Reactions involve acid donating a proton to a base

Lewis Acids and Bases

• Lewis Acid: electron pair acceptor
• Lewis Base: electron pair donor

Amphiprotic Solvents and Solutes

• Amphiprotic Solvents: exhibit both acidic and basic properties (e.g. water, methanol, ethanol, glacial acetic acid)
• Amphiprotic Solutes: act as both acids and bases (e.g. HCO3⁻, HPO₄²⁻)

pH Scale

• pH = -log[H+]
• pAnything = -log(Anything)
• pKw = -logKw at 25°C = 14.00
• Kw = [H+][OH-]
• pKw = pH + pOH = 14
• Blood pH (at 37°C) is 7.35-7.45 (slightly basic).

Salts of Strong Acids and Bases

• The pH of salts of strong acids or bases remains constant (pH=7).
• Ions of these salts do not react with water.

Weak Acids and Bases

• A weak acid/base partially dissociates in water.
• Equilibrium constant is small
• Amount dissociated is negligible compared to the original concentration.

pH Calculations - Examples

• Examples demonstrate calculations for strong and weak acids/bases using equilibrium expressions.
• Calculations consider the contribution of water dissociation to the overall H+ concentration, and use the assumption that x is small
• Examples demonstrate how to find pOH and then pH using equilibrium constants.

Salts of Weak Acids and Bases

• Salts of weak acids and bases are not neutral.
• Conjugate bases of weak acids can hydrolyze in water to increase the OH⁻ concentration
• Salts and bases influence pH

Buffer Solutions

• A buffer resists changes in pH upon addition of small amounts of acid or base.
• Buffer solutions contain a weak acid and its conjugate base, or a weak base and its conjugate acid
• The Henderson-Hasselbalch equation relates pH to the pKa and concentrations of the weak acid and conjugate base

Polyprotic Acids and Their Salts

• Polyprotic acids can donate more than one proton.
• Stepwise dissociation; each step has its own equilibrium constant
• Dissociation constants become progressively smaller as a result of the increasing negative charge.

Acid-Base Titrations

• Calculate titration curves.
• Recognize acid-base color indicators.
• Calculate titration curves with weakly acidic drugs vs. strong base.
• Calculate titration curves with weakly basic drugs vs. strong acid.
• Calculate equations for weak acidic/basic drugs' titrations.
• Calculate & construct polyfunctional acidic/basic titration curves (including drugs).

Titration

• A standard solution with known concentration (titrant) is used to determine the concentration of an unknown solution (analyte).
• The reaction occurring is a neutralization reaction.
• Acidimetry/Alkalimetry
• The quantitative determination of basic/acidic drugs respectively

Volumetric Analysis - Acid-Base Titrations - Additional Topics

• Calculate the pH before a titration begins.
• Explain how to find pH during a titration before reaching the equivalence point
• Determine pH at equivalence point
• How to find pH after equivalence point

Titration Curves for Strong Acids and Bases

• Strong acids and bases completely dissociate
• Stoichiometric ratio of the acid-base reaction is considered.
• Only one equilibrium is considered in the calculations (ion product constant, Kw)

Titration Curves for Weak Acids/Weak Bases

• Weak acids and bases partially dissociate.
• Henderson-Hasselbalch equation is used in the buffer region to calculate pH.
• Consider hydrolysis at the equivalence point.

Polyfunctional Acids/Bases

• Polyprotic acids/bases have multiple ionizable groups.
• Equivalence points may occur at multiple pH values for polyprotic acids/bases.

Amino Acids

• Amino acids are polyprotic.
• Zwitterions.

Appendix - Aqueous Titrations from USP

• Provides specific procedures for direct and indirect titrations of different substances, including quantities, indicators and calculations using standardized solutions. Note: these are USP specific titration methods.

This quiz covers the fundamental concepts of acid-base equilibria, including the calculation of pH values for various acidic and basic drugs. It explores the use of the Henderson-Hasselbalch equation, buffering capacity, and polyprotic species. Test your knowledge on calculating pH and understanding drug properties related to acidity and basicity.