Chemical Kinetics Quiz

Introduction to Drug Degradation

• Pharmaceutical products must meet three key requirements:
  • Efficacy: Must achieve optimum therapeutic level for a specified time.
  • Safety: Should minimize or eliminate adverse side effects.
  • Stability: Retain properties during storage.
• Stability ensures efficacy and safety.

Stability of Pharmaceutical Preparations

• Stability is the capability of a formulation to remain within specific limits in a given container-closure system at a certain temperature throughout its shelf life.
• Drug properties include physical, chemical, microbiological, toxicological, disintegration, and dissolution properties.
• Shelf life is the period between manufacture and expiry dates.
• Stability analysis determines shelf life.

Stability Categories

• Drug substances are studied under three categories of stability:
  • Solid-state stability of the drug alone.
  • Compatibility studies (drug + excipients).
  • Solution-phase stability.

Importance of Stability Studies

• Formulating optimum conditions (temperature, light, humidity) for storage
• Selecting appropriate containers and closures (glass, plastic, clear/opaque, cap liners).
• Predicting shelf life.
• Avoiding drug-excipient interactions.
• Stabilizing drugs against degradation.
• Ensuring container closure system suitability.
• Guaranteeing patient safety.
• Preventing economical repercussions.
• Essential quality attribute

Criteria For Acceptable Levels of Stability

• Chemical: Active ingredients maintain chemical integrity and labeled potency.
• Physical: Original physical properties (appearance, palatability, uniformity, dissolution, and suspendability) remain unchanged.
• Microbiological: Sterility or resistance to microbial growth is retained.
• Therapeutic: The therapeutic effect remains unchanged.
• Toxicological: No significant increase in toxicity occurs.

Factors Affecting Drug Stability

• Temperature: High temperatures can accelerate oxidation, reduction, and hydrolysis reactions leading to degradation.
• pH: Acidic and alkaline pHs can influence the rate of decomposition.
• Moisture: Impacts drug stability.
• Light: Energy and thermal effects can cause oxidation.
• Dosage forms: Solid dosage forms are more stable than liquid dosage forms due to reduced water content.
• Concentration: Rate of degradation is constant across different concentrations of the same drug.
• Drug incompatibility: Reactions between drug components or components/container affects stability.
• Oxygen: Exposure to oxygen affects stability.

Degradation Studies

• Most drugs are susceptible to chemical decomposition in their dosage forms.
• Degradation leads to loss of potency and generation of impurities.
• Impurities are controlled by understanding degradation rates and mechanisms, implementing stabilization strategies.
• Kinetic studies determine the speed/rate of chemical reactions and conditions affecting this.

Chemical Kinetics

• Chemical kinetics deals with the rates of chemical reactions.
• Chemical kinetics includes:
  • Rate laws
  • Rate-affecting factors like temperature, pressure, concentration, and catalysts
  • Reaction mechanisms (steps).

Applications of Chemical Kinetics

• Drug stability
• Drug dissolution
• Drug release
• Pharmacokinetics
• Drug action
• Selecting optimum conditions for industrial processes leading to maximum yields.

Speed or Rate of Reaction

• The rate of a chemical reaction is the change in concentration of a reactant or product with time, expressed in molarity per second.
• Consider a reaction A → B
• The concentration of reactant A decreases with time, while the concentration of product B increases with time.

Types of Rates

• Initial rates: Rates measured at the beginning of a reaction, dependent on initial reactant concentrations.
• Average rates: Rates based on the overall change in concentration over a period of time.
• Instantaneous rates: Measured at a specific moment in time with the smallest time interval, Δt approaching 0.

Reaction Rates

• Average rates are calculated by measuring the change in concentration of a reactant over a given time frame (e.g. 50 seconds).
• The average rate reflects the rate of the reaction over the duration of the interval.

Average Reaction Rates

• The average rate is calculated using the formula Δ[A]/Δt, where Δ[A] is the change in concentration of reactant A and Δt is the time interval.

Reaction Rates from a Graph

• The rate of the reaction from a graph can be calculated at different points by calculating the slope of a tangent to the curve of the concentration versus time plot at these points.

Factors Affecting the Rate of a Chemical Reaction

• Nature of reactant: Ionic substances react quicker than covalent substances.
• Concentration of reactants: Rate of reaction is proportional to concentration (and partial pressure in gases).
• Temperature: Increased temperature increases reaction rate.
• Presence of catalyst: Catalysts alter reaction rate.
• Surface area of reactants: Larger surface area increases reaction rate.
• Radiation: Affects reaction rate.

The Rate Law or Rate Expression and Rate Constant

• The rate law expresses the relationship between reaction rate and reactant concentrations.
• The rate law includes the rate constant, k, and exponents representing the reaction order with respect to each reactant.
• The rate law helps determine the overall order of the reaction. It is independent of concentration, but depends on temperature.

Reaction Order

• The sum of exponents of reactant concentrations in the rate law equation determines the overall order of a reaction.
• Reaction order can be zero, first, second, or fractional order.
• Reaction order is experimentally determined, and cannot be solely predicted from the balanced equation.

Order of a Reaction - Different classifications

• Reactions can be:
  • Zero-order: Rate is independent of reactant concentrations.
  • First-order: Rate is directly proportional to the concentration of a single reactant.
  • Second-order: Rate is directly proportional to the square of the concentration of a single reactant or the product of the concentrations of two reactants.
• Order of a reaction can be determined using experimental procedure, and from the rate law.

Types of Reactions

• Elementary reactions: Occur in a single step.
• Complex reactions: Occur in multiple steps, involving intermediate products.

Molecularity of a Reaction

• Molecularity: The number of reactant molecules involved in an elementary reaction.
• Molecularity can be unimolecular (one molecule), bimolecular (two molecules), or termolecular (three molecules).
• While molecularity is about the reaction mechanism, the order reflects the overall rate law dependence.

Differences between Order and Molecularity

• Order is the sum of reactants' exponents in the rate law, while molecularity is the number of reactants in an elementary step.
• Order is experimentally determined, molecularity is theoretical calculation.
• Order can be fractional, molecularity is always a whole number.
• Order is for entire reaction, molecularity is for individual steps.

Methods of Determining Reaction Order

• Initial rate method: Change concentration of one reactant while keeping others constant. Measure the corresponding initial rate, and compare.
• Integrated rate laws: Determining relationship between concentration and time from reaction rate law.
• Substitution methods: Evaluate reaction orders and rate equations by substituting values.
• Half-life method: Calculate half-life and compare dependence on initial concentration for different reaction orders.

Zero-Order Reaction

• The rate of a zero-order reaction is independent of the concentration of reactants.
• The rate remains constant throughout the reaction.
• The graph shows a linear decrease in reactant concentration over time.

First-Order Reaction

• The rate of a first-order reaction is directly proportional to the concentration of a single reactant.
• The rate decreases with time, and the plot of reactant concentration versus time is curved decreasing.

Second-Order Reaction

• The rate of a second-order reaction is proportional to the square of the concentration of a single reactant or the product of the concentrations of two reactants.
• The rate decreases with time, and the rate versus concentration graph shows a continuously increasing slope with decreasing concentration.

Pseudo-Order Reaction

• A pseudo-order reaction appears to be a lower-order reaction than the actual reaction due to the large excess of one reactant.
• The pseudo-order is usually a first order from a second order reaction.

The Half-Life of a Reaction

• Half-life (t1/2): The time required for the concentration of a reactant to decrease to half of its initial value.
• Half-life value is dependent on the reaction order and the initial concentration.
• Zero-order reactions, half-life varies directly with initial concentration
• First-order reactions, half-life is constant and independent of initial concentration
• Second-order reactions, half-life varies inversely with initial concentration.

Complex Reactions

• Complex reactions occur in multiple steps and are formed from several elementary reactions.
• They may be parallel, which happens at the same time, consecutive, which is in a series, or reversible, which means they can proceed in multiple directions.