F2_kinetik_2024

Department Overview

Department of Physics, Chemistry and Pharmacy, SDU

Course: KE538 - Fysisk Kemi for Farmaci

• Instructor: René Holm (reho@sdu.dk)

Course Topics Include:

• Kinetics: The study of the rates at which chemical reactions occur, examining how factors such as concentration, temperature, and presence of catalysts affect reaction speed.

• Thermodynamics: Understanding the principles governing energy transfer and the conversion of energy within chemical reactions, including concepts such as enthalpy, entropy, and free energy.

• Mixtures: Analysis of different types of mixtures, including homogeneous and heterogeneous mixtures, and the significance of solubility, concentration, and interactions between components.

• Ionic Solutions: Exploration of the behavior of ionic compounds in solution, focusing on their dissociation into ions, conductivity, and factors affecting solubility.

• Acid-Base Equilibrium: Examination of the principles of acidity and basicity, pH scale, buffer solutions, and the implications of acid-base reactions in pharmaceutical contexts.

Key Concepts in Kinetics

• Reaction Order: Refers to the power to which a reactant concentration is raised in the rate law equation.

  • 0th Order: Rate is independent of the concentration of reactants, often occurring in reactions with constant rate regardless of reactant concentration.

  • 1st Order: Rate is directly proportional to the concentration of one reactant, typical in many simple decay processes.

  • 2nd Order: Rate depends on the concentrations of two reactants or the square of a single reactant concentration.

• Initial Rate: The rate of reaction measured at the very beginning, which provides insights into kinetics before significant changes occur.

• Pseudo Order: Occurs when one reactant's concentration is much larger than that of the others, allowing simplifications in calculations.

• Half-life (T½) & Shelf-life: Critical concepts in understanding how long a substance remains active or effective and the factors influencing these durations.

• Equilibrium: Dynamic state where the rate of the forward reaction is equal to that of the reverse reaction, critical for understanding reaction reversibility.

• Activation Energy: The minimum energy required for a reaction to occur, with implications for rates depending on temperature and catalysts.

• Stability Testing Requirements: A heavily regulated area in pharmaceuticals, following stringent guidelines to ensure product integrity over time. Relevant ICH guidelines include:

  • ICH Q1A: Stability Testing of New Drug Substances and Products

  • ICH Q1B: Photostability Testing

  • ICH Q1C: Stability for New Dosage Forms

  • ICH Q3A/B: Impurities in New Drug Substances/Products

  • ICH Q5C: Quality of Biotechnological Products

  • ICH Q6A/B: Specifications for New Drug Substances/Products

Reaction Kinetics Overview

• Formation Reactions: Expressed as R → P, with a mathematical representation of the rates of disappearance of R and appearance of P.

  • Rate Expression:v = -(\dfrac{\Delta R}{\Delta t}) = (\dfrac{\Delta P}{\Delta t})

Reaction Order and Rate Laws

• General Rate Law: For reactions represented as A + B → C + D, the rate is determined as Rate = k [A]ᶦ [B]ʲ, where the overall reaction order is i + j.

Reaction Orders: Overview

• 0th Order Reactions:

  • Example: A → P

  • Rate = -(\dfrac{dA}{dt}) = k, indicating a constant rate independent of concentration.

• 1st Order Reactions:

  • Example: dA/dt = -k[A]

  • Rate varies with the concentration of a single reactant, with time⁻¹ units for k.

Calculating Half-life

• Half-life (T½) for reactions:

  • For first-order reactions: T½ = (\dfrac{0.693}{k})

  • For second-order reactions: T½ = (\dfrac{1}{k[A]₀})

Pseudo Reactions

• Pseudo First Order: When one reactant’s concentration is considerably higher than the others, allowing it to be treated as a constant (e.g., v = k’[A]).

• Pseudo Zero Order: In instances where the concentration of reactant [A] remains constant throughout the reaction.

Methods for Determining Reaction Order

• Integration Method: Involves using accumulated data and inserting into integrated forms of equations to find order nature.

• Graphical Method: Involves plotting concentration vs. time and identifying linearity for determining the order of the reaction.

Shelf-life of Pharmaceuticals

• Defined as the time span over which a formulation remains stable, generally acceptable degradation thresholds are set at 10% in the US and 5% in the EU.

• Calculating examples for shelf-life that derive from reactions of different orders are critical for regulatory compliance and product safety.

Recap of Key Learning Points

• Discussion on integrated rate laws for various order reactions (0th, 1st, 2nd).

• Understanding pseudo rates and methodologies for establishing reaction rates.

• Importance of T½ and shelf-life regulations within the contexts of EU and US standards.

• Familiarity with the Arrhenius equation, detailing temperature dependencies affecting reaction rates, which can guide pharmaceutical development and stability assessments.