Buffer Solutions and pH Calculations

Buffer Solutions

• Buffers are compounds or mixtures, present in a solution, resisting pH changes when small quantities of acid or alkali are added.
• Buffer action is the resistance to change in pH.
• Many biological and chemical reactions require a constant pH to proceed.
• Drugs in parenteral solutions require specific pH levels for stability.
• Buffers are crucial in these systems to maintain a constant pH.
• This doesn't mean the pH of a buffer or medium doesn't change, only that the change is less than a solution without a buffer.

The Buffer Equation

• A weak acid and its conjugate base (salt) or a weak base and its conjugate acid act as buffers;
• pH = pKa + log [salt]/[acid] (for a weak acid)
• pH = pKw - pKb + log [base]/[salt] (for a weak base)
• Brackets [ ] denote moles or molar concentrations.

The Buffer Equation - Considerations

• Buffer solutions are not normally prepared from weak bases and their salts due to instability and volatility.
• Their pH depends on pKₐ, which is often affected by temperature changes.

Numerical Example (1)

• Calculate the pH of an acidic buffer using pKa = 4, acid concentration of 0.01, and sodium salt concentration of 0.05.
• pH = 4 + log (0.05/0.01) = 4.7

Buffering Action

• A small amount of strong acid or base added to water significantly changes the pH.
• Such systems lack buffer action.
• Example: 1 mL of 0.1 N HCl added to 100 mL of pure water reduces pH from 7 to 3.
• Weak acid partially dissociates (e.g., acetic acid).
• The dissociation constant (Ka) describes this.

Buffering Action Continued

• Sodium acetate added to acetic acid raises acetate anion concentration.
• This common ion suppresses the acid dissociation.
• The resulting system functions as an acetate buffer.
• Adding a strong acid (H⁺ or H₃O⁺) or base (OH⁻) to an acetate buffer produces minor pH changes.

Numerical Example (2)

• Calculate the pH change of an acetate buffer (0.1 mole acetic acid and 0.1 mole sodium acetate).
• pKa of acetic acid is 4.76.
• No acid/base added: pH = 4.76
• 0.01 M HCl added: pH = 4.673
• 0.01 M NaOH added: pH = 4.847

Factors Influencing Buffer pH

• Adding neutral salts alters buffer pH by changing ionic strength.
• Moderate water addition may cause slight positive or negative deviations.
• Temperature affects buffer pH, with acetate buffers increasing and boric acid/sodium borate buffers decreasing with temperature.

Drugs as Buffers

• Salicylic acid (sodium salicylate)
• Ephedrine base (ephedrine hydrochloride)

Universal Buffer

• A mixture of weak acids with similar pKa values and overlapping buffer regions, offering buffer action over a wide pH range.
• Citric acid (pK₁ = 3.15, pK₂ = 4.78, pK₃ = 6.40) demonstrates this property.

Buffer Capacity

• Measures the resistance of a buffer to pH changes.
• Also known as buffer efficiency, buffer index, or buffer value.
• β = ΔB/ΔpH
• ΔB is the gram equivalents of strong base to change pH by ΔpH

Van Slyke's Equation

• β = 2.3 C Ka[H₃O⁺]/[(Ka +[H₃O⁺])²]
• C is the total buffer concentration (acid + salt).

Numerical Example (3)

• Calculate buffer capacity for 0.10 mole each of acetic acid and sodium acetate per liter (C =0.20 mole/L) and a dissociation constant of 1.75 x 10⁻⁵, at a hydrogen ion concentration of 1.75 x 10⁻⁵ (pH = 4.76)
• β = 0.115

Maximum Buffer Capacity

• β max = 0.576 C (C = total buffer concentration)

Numerical Example (4)

• Calculating the maximum buffer capacity for the buffer in example 3.
• β max = 0.576 x 0.20 = 0.1152

Buffers in Pharmaceuticals (In vivo)

• Blood maintains a pH of ~7.4 via primary buffers (plasma) and secondary buffers (erythrocytes).
• Plasma contains carbonic acid/bicarbonate and sodium salts of phosphoric acid.
• Specific ratio between bicarbonate and carbonic acid at a given pH, temperature allows for calculations.

Buffers in Pharmaceuticals (Continued)

• Plasma proteins function as buffers by combining with bases
• Erythrocytes include hemoglobin/oxyhemoglobin, and acid/alkali potassium salts of phosphoric acid.
• Specific buffer capacity values are available for whole blood components.

Buffers in Pharmaceuticals (In vivo cont)

• Significant pH deviations could indicate health complications (below 7.0 or above 7.8)
• Low pH of blood associated with diabetic coma.

Pharmaceutical Buffers

• Solutions used in medicine might require adjusted pH.

Influence of Buffer Capacity and pH on Tissue Irritation

• Solutions applied to tissues or given parenterally can cause irritation if pH differs too much from body fluids.
• Minimizing irritation requires lower buffer capacity of the solution and a smaller volume.
• High volume and higher buffer capacity in the body fluid help prevent irritation.

Influences of Buffer Capacity and pH on Tissue Irritation cont

• Parenteral solutions for injection into the blood are often not buffered, or buffered at a low capacity.
• This allows blood’s buffers to regulate the solutions pH effectively

Drug Stability

• Acid/base reactions may decrease drug stability
• pH adjustment is critical during sterilization.
• Certain solutions are highly unstable if too basic or neutral

Drug Stability Continued

• Cocaine hydrochloride solutions are stable for two months at pH 5.7 but significantly degrade (30%) when buffered to pH 6 .

Drug Activity

• Ionized and non-ionized drug versions can have different pharmacological effects
• Weak acid/base drugs will have a required environment to best function
• Mandelic, benzoic and salicylic acid function as antibacterial agents in acidic environment

Drug Absorption

• Drug ionization and lipoid solubility affect absorption rate and passage through membranes.
• Weak organic acids/bases preferentially dissolve in lipids and are thus absorbed more easily through cell membranes
• Completely ionized drugs are absorbed less readily

Drug Absorption - continued

• pH of the environment, like stomach, intestinal fluid, plasma affects which form of the drug is readily absorbable.
• Drug's rate of absorption correlates their ionization constants and often can be predicted.

Stability vs Optimum Therapeutic Response

• Drug stability levels for use in the eyes can be far lower than the optimum pH required for therapeutic effect
• Some situations may compromise required stability and efficiency to reach maximum effect

pH and Solubility

• Bases tend to be more soluble at lower pHs;
• Higher pH results in more non-ionized base,
• Precipitation may occur if the concentration of the base exceeds its solubility capabilities

Buffered Isotonic Solutions

• Isotonic solutions maintain cell shape and volume
• Hypertonic solutions cause cell shrinkage
• Hypotonic solutions cause cell swelling and possible lysis

Boric Acid Solutions

• 2% Boric acid solution has the same osmotic pressure as blood
• Solutions are considered iso-osmotic with blood if boric acid molecules freely pass through erythrocyte membranes.
• Only when blood cell membranes are permeable to the solvent will solutions be considered isotonic

Distinction Between Isoosmotic and Isotonic

• Iso-osmotic solutions maintain the same osmotic pressure as the solution inside the cell
• Isotonic solutions maintain the same volume of the cell content even when in contact with a solution of the same osmotic pressure.

Measurement of Tonicity

• Hemolysis (bursting) of red blood cells is used to examine tonicity in solutions.
• Colligative properties, such as freezing point depression, are also used to determine tonicity.

Calculating Tonicity Using Liso Values

• Introducing new factor (L) in freezing point depression equations to quantify tonicity of solutions with electrolytes
• L₁₀₀ gives a specific freezing point lowering in solutions relative to body fluid

Methods for Adjusting Tonicity and pH

• Method 1: Sodium chloride or other substance added to lower the freezing point to be isotonic with body fluids.
• Method 2: Adding water to the drug to reach a final isotonic volume
• These methods have equations for calculating isotonic solution volume from drug concentrations and constants.

Class 1 Methods: Cryoscopic Method

• Example calculation to determine needed NaCl to make a drug isotonic.
• Proportion of freezing point depression for the drug compared to that of NaCl is used.

Class 1 Methods: Sodium Chloride Equivalent Methods

• The tonic equivalent of a drug is compared to an equivalent amount of NaCl to make calculations easier
• Calculations to determine the ratio of sodium chloride equivalent to that of the drug.

Class 2 Methods: White-Vincent Method

• Water is added to adjust tonicity.
• The volume of isotonic solution is calculated for a given amount of drug.

Class 2 Methods: General Notes

• When multiple ingredients exist the isotonic volumes from adding the ingredients are additive

Example Calculation

• Example for calculate isotonic solution for mixture

Test your knowledge on buffer solutions and their properties with this quiz. You will explore the behavior of acetate buffers, effects of adding acids and bases, and calculate pH values based on given concentrations. Perfect for chemistry students wanting to deepen their understanding of buffer chemistry.