Kinetics and Drug Stability One Shot Notes and MCQs
Kinetics and Drug Stability
Pharmaceutical kinetics studies the rate at which drugs undergo chemical changes. Drug stability is critical in ensuring that a drug maintains its safety, efficacy, and quality over time. Knowledge of kinetics and factors affecting stability enables the design of stable formulations, safe storage conditions, and accurate expiration dates for drugs.
1. General Considerations and Concepts
A. Chemical Kinetics
- Definition: Chemical kinetics studies the rate of chemical reactions and the factors influencing them.
- Rate of Reaction (v): Refers to the change in concentration of reactants/products per unit time. In drug degradation, it is crucial to determine how fast a drug loses its potency over time.
B. Rate Law and Order of Reactions
- Zero-Order Reactions: The reaction rate is constant and independent of the concentration of reactants.
Rate=k\text{Rate} = k - First-Order Reactions: The reaction rate is directly proportional to the concentration of one reactant.
Rate=k[A]\text{Rate} = k[A] - Second-Order Reactions: The reaction rate depends on the concentration of two reactants or the square of the concentration of a single reactant.
Rate=k[A]2\text{Rate} = k[A]^2
C. Importance in Pharmacy
- Understanding reaction kinetics helps determine the degradation pathways of drugs, the best storage conditions, and the shelf life, ensuring patient safety and effective dosage.
2. Half-Life Determination
Half-life (t₁/₂) is the time required for the concentration of a drug to reduce to half its initial value. It is a crucial parameter for determining dosing intervals, drug stability, and expiration dates.
- Zero-Order Half-Life: t1/2=[A]02kt_{1/2} = \frac{[A]_0}{2k} Half-life decreases as concentration decreases.
- First-Order Half-Life: t1/2=0.693kt_{1/2} = \frac{0.693}{k} Half-life is constant regardless of concentration.
- Second-Order Half-Life: t1/2=1k[A]0t_{1/2} = \frac{1}{k[A]_0} Half-life depends on the initial concentration and decreases with decreasing concentration.
The half-life of a drug helps in predicting stability, frequency of dosing, and designing appropriate storage conditions.
3. Factors Affecting Drug Stability
Drug stability is influenced by various environmental and chemical factors that can accelerate or decelerate degradation.
A. Temperature
- Arrhenius Equation: Shows the relationship between temperature and reaction rate: k=Ae−EaRTk = A e^{-\frac{E_a}{RT}}
- Impact: Higher temperatures generally increase reaction rates, leading to faster degradation. For every 10°C rise, the rate of reaction may double, known as the Q₁₀ rule.
- Storage: Drugs are stored at lower temperatures to reduce degradation rates (e.g., refrigeration for heat-sensitive drugs).
B. Light (Photodegradation)
- Mechanism: Light, especially UV radiation, can cause drugs to decompose by breaking chemical bonds.
- Impact: Drugs sensitive to light, such as certain antibiotics and vitamins, undergo faster degradation when exposed to light.
- Storage: Light-sensitive drugs are stored in amber-colored containers to block UV rays.
C. Solvent (Hydrolysis and Solvolysis)
- Hydrolysis: Water can act as a reactant in the degradation of drugs, especially in solution. Commonly affected drugs include esters, amides, and lactams.
- Solvolysis: Solvents other than water (e.g., alcohol) can also cause drug degradation.
- Impact: Liquid formulations are more prone to hydrolysis compared to solid forms.
- Storage: Solid formulations are often preferred, and moisture-resistant packaging is used for hydrolytic drugs.
D. Catalytic Species (Metal Ions, Enzymes, and pH)
- Metal Ions: Trace metals (e.g., Fe³⁺, Cu²⁺) can catalyze drug oxidation and promote degradation.
- Enzymes: Some drugs degrade in the presence of enzymes, which catalyze reactions. E.g., proteins and peptides may degrade due to proteolytic enzymes.
- pH: Drug stability varies with pH, as some drugs are stable only within a specific pH range. pH can affect the ionization and reactivity of drug molecules.
- Storage: Buffering agents and chelating agents (e.g., EDTA) are often added to stabilize pH-sensitive drugs and bind catalytic metal ions.
E. Humidity
- Impact: High humidity can lead to moisture absorption, accelerating hydrolysis and affecting drug stability.
- Storage: Desiccants are often included in packaging to control humidity, particularly for hygroscopic drugs.
4. Accelerated Stability Studies
Accelerated stability studies are conducted to predict a drug’s shelf life within a shorter period by subjecting it to elevated temperatures, humidity, and other stress conditions. These studies allow manufacturers to estimate a drug’s shelf life and determine expiration dates.
A. Purpose of Accelerated Stability Testing
- To predict the shelf life of new formulations.
- To identify potential degradation products and pathways.
- To understand the stability profile under stress conditions.
B. Process
- Storage Conditions: Typically, drugs are stored at high temperatures (40°C or above) and high humidity (e.g., 75% relative humidity).
- Testing Intervals: Samples are analyzed at regular intervals to monitor degradation.
- Extrapolation: Based on data from accelerated conditions, the stability of a drug under standard storage conditions is estimated using the Arrhenius equation.
C. Parameters Monitored
- Assay: Determines the potency and concentration of the drug over time.
- Impurity Profiling: Checks for degradation products.
- Physical Changes: Monitors changes in color, odor, or consistency.
5. Expiration Dating
Expiration dating is based on stability data, indicating the time a drug product is expected to remain within specified potency limits.
A. Determination of Expiration Date
- Expiration dates are set based on the stability of a drug under prescribed storage conditions.
- Regulatory authorities, such as the FDA and ICH, provide guidelines for stability testing to set expiration dates.
B. Shelf Life and Beyond-Use Date
- Shelf Life: The period a drug remains effective, safe, and stable under specified storage conditions.
- Beyond-Use Date: Often assigned to compounded or reconstituted drugs, this date is generally shorter than the shelf life and ensures potency after opening or mixing.
C. Labeling and Storage Instructions
- Expiration dates and storage conditions are often included on drug labels to maintain stability and ensure patient safety.
MCQs on Kinetics and Drug Stability
- In a first-order reaction, the rate of reaction depends on:
- a) The square of the concentration of the reactant
- b) The concentration of the reactant
- c) The concentration of the product
- d) None of the above
Answer: b
- Which of the following is true for a zero-order reaction?
- a) Rate is independent of the concentration of reactants
- b) Rate is dependent on the concentration of reactants
- c) Rate decreases as the concentration increases
- d) None of the above
Answer: a
- The half-life of a first-order reaction is:
- a) Proportional to the initial concentration
- b) Constant, regardless of concentration
- c) Inversely proportional to the concentration
- d) Directly proportional to the square of the concentration
Answer: b
- The rate constant of a reaction can be determined using the Arrhenius equation. Which factor does NOT influence this rate constant?
- a) Temperature
- b) Activation energy
- c) The presence of a catalyst
- d) Reaction order
Answer: d
- Which of the following can increase the rate of a chemical reaction?
- a) Lowering the temperature
- b) Removing catalysts
- c) Increasing reactant concentration
- d) Using an inhibitor
Answer: c
- A drug undergoes zero-order kinetics if:
- a) Its degradation rate is proportional to its concentration
- b) Its degradation rate is constant and independent of concentration
- c) It decomposes rapidly at high concentration
- d) It does not degrade at all
Answer: b
- The half-life (t₁/₂) of a zero-order reaction is:
- a) Inversely proportional to the initial concentration
- b) Directly proportional to the initial concentration
- c) Constant for any concentration
- d) Dependent on the concentration of product
Answer: b
- Which equation is used to study the influence of temperature on reaction rates?
- a) Michaelis-Menten equation
- b) Arrhenius equation
- c) Henderson-Hasselbalch equation
- d) Nernst equation
Answer: b
- In accelerated stability studies, a drug is stored at high temperatures to:
- a) Increase its stability
- b) Estimate its stability under normal storage conditions
- c) Reduce its shelf life
- d) Check the impact of refrigeration
Answer: b
- The Q₁₀ rule states that for every 10°C increase in temperature, the reaction rate:
- a) Doubles
- b) Halves
- c) Triples
- d) Remains constant
Answer: a
- Which factor does NOT affect the rate of drug degradation?
- a) Light
- b) Temperature
- c) Magnetic field
- d) Catalysts
Answer: c
- What is the purpose of using amber-colored containers for drug storage?
- a) To prevent moisture absorption
- b) To reduce microbial growth
- c) To block UV and visible light
- d) To enhance the drug’s color
Answer: c
- A drug that undergoes photodegradation is:
- a) Stable in the presence of light
- b) Sensitive to light exposure
- c) Resistant to hydrolysis
- d) Stable under all conditions
Answer: b
- For a second-order reaction, the rate depends on:
- a) The square of the concentration of one reactant
- b) The sum of the concentrations of two reactants
- c) The product of the concentration of two reactants
- d) Only on the concentration of the catalyst
Answer: c
- The activation energy (Ea) of a reaction is:
- a) The minimum energy required to initiate a reaction
- b) The energy released during the reaction
- c) The difference in energy between reactants and products
- d) The maximum energy of the reactants
Answer: a
- The degradation of a drug is accelerated in the presence of:
- a) Desiccants
- b) Catalytic metals
- c) Buffers
- d) Light-absorbing agents
Answer: b
- The rate constant (k) for a reaction at room temperature is lower than at higher temperatures because:
- a) Molecules move slower at lower temperatures
- b) Activation energy is reduced at lower temperatures
- c) Lower temperatures increase reaction rates
- d) The number of collisions is increased
Answer: a
- A common technique used in accelerated stability studies is:
- a) Increasing light exposure
- b) Reducing temperature
- c) Storing at high humidity and temperature
- d) Storing under ambient conditions
Answer: c
- Half-life for a zero-order reaction depends on:
- a) Initial concentration of the reactant
- b) Temperature only
- c) Presence of light
- d) The reaction mechanism
Answer: a
- For which type of reaction is the half-life constant and independent of concentration?
- a) Zero-order reaction
- b) First-order reaction
- c) Second-order reaction
- d) Third-order reaction
Answer: b
- The shelf life of a drug is defined as the time during which:
- a) 10% of the drug is degraded
- b) 50% of the drug is degraded
- c) The drug remains stable and effective
- d) The drug loses its potency completely
Answer: c
- In the Arrhenius equation, the term ‘A’ represents:
- a) The reaction order
- b) The frequency factor
- c) Activation energy
- d) Temperature
Answer: b
- The rate-determining step in a reaction is:
- a) The fastest step
- b) The slowest step
- c) The final step
- d) Independent of temperature
Answer: b
- The degradation of ascorbic acid in solution is affected by:
- a) Temperature and oxygen
- b) Magnetic field and light
- c) pH and UV radiation
- d) Humidity only
Answer: a
- Drug stability testing is performed to establish:
- a) Chemical purity only
- b) Expiration date and storage conditions
- c) Efficacy of the drug in humans
- d) Drug interactions
Answer: b
- A drug stored in a solution form is more likely to undergo which type of degradation?
- a) Hydrolysis
- b) Photodegradation
- c) Thermal degradation
- d) Oxidation
Answer: a
- If a reaction’s rate doubles when the temperature is increased by 10°C, it follows:
- a) Michaelis-Menten kinetics
- b) Arrhenius behavior
- c) Zero-order kinetics
- d) None of the above
Answer: b
- Photodegradation of drugs can be minimized by:
- a) Storing at high temperatures
- b) Using dark-colored containers
- c) Adding a preservative
- d) Increasing pH
Answer: b
- What does the expiration date on a drug indicate?
- a) When the drug becomes completely inactive
- b) When the drug is no longer effective
- c) When the drug has 90% of its original potency
- d) When the drug must be discarded
Answer: c
- In the Arrhenius equation, as the activation energy (Ea) decreases, the reaction rate:
- a) Increases
- b) Decreases
- c) Remains constant
- d) Depends on the frequency factor
Answer: a
- Which factor is NOT considered in stability testing?
- a) Humidity
- b) Solubility
- c) Temperature
- d) Light
Answer: b
- The term ‘expiration date’ refers to the date until which a drug is expected to remain:
- a) Pure and safe
- b) Stable, effective, and safe
- c) In its original packaging
- d) Completely unchanged
Answer: b
- The rate constant (k) is expressed in units of:
- a) Time
- b) Volume
- c) Concentration
- d) Concentration per time
Answer: d
- Humidity affects stability by:
- a) Reducing hydrolysis rates
- b) Causing degradation in solid drugs
- c) Improving solubility
- d) Decreasing temperature sensitivity
Answer: b
- In accelerated stability studies, samples are generally analyzed at intervals of:
- a) 1 day
- b) 1 month
- c) 3 months
- d) 6 months
Answer: c
Also, Visit:
B. Pharma Previous Year Question Paper