Drug Stability and Expiration Dates Quiz

Drug Stability and Expiration Dates

• Drug Stability: Ability of a pharmaceutical product to maintain its properties and characteristics during storage and use.
• Shelf life: Time period during which a pharmaceutical product remains within specified parameters.
• Expiration Date: Date after which a drug should not be used and needs to be discarded.
• Drug Instability: Degradation of drug properties and characteristics over time, which can lead to reduced potency or adverse effects.
• Factors Affecting Drug Stability:
  • Drug-excipient interactions
  • Environmental factors (light, oxygen, moisture)
  • Packaging materials
• Types of Drug Instability:
  • Physical Instability: Changes in appearance, texture, or physical properties.
  • Chemical Instability: Decomposition or reactions leading to changes in potency.
  • Microbial Instability: Growth of microbes or formation of endotoxins.
  • Therapeutic Instability: Loss of drug effectiveness.
  • Toxicological Instability: Conversion to toxic substances.

Physical Drug Instability

• Multiple Phase Dosage Forms: Susceptible to physical instability, e.g., emulsions, semisolids, suspensions.
  • Emulsions: Creaming, aggregation, coalescence.
  • Semisolids: Phase separation.
  • Suspensions: Caking, sedimentation.
• Other Dosage Forms:
  • Tablets: Meling, cracking, chipping.
  • Capsules: Shell softening or hardening, seal swelling.
  • Powders and Granules: Caking, odor/color changes, swelling.
  • Liquid Dosage Forms: Loss of homogeneity, microbial growth, turbidity, gas formation.
  • Emulsions: Phase separation.
  • Suspensions: Caking, excessive crystal growth.
  • Semisolids: Discoloration, viscosity change, odor change.
  • Creams: Phase separation, shrinkage, greasiness, sandiness, microbial growth.
  • Ointments: Bleeding, greasiness, sandiness.
  • Suppositories: Softening, oil stains, hardening.
  • Sterile Liquids: Cloudiness, particle formation, color change, particulate matter, gas formation, seal integrity loss.

Pharmacist's Role in Drug Stability

• Develop formulations with maximum stability.
• Determine optimum storage conditions.
• Select appropriate container for dispensing.
• Predict shelf life of drug products.
• Establish Beyond Use Dates for compounded products.
• Identify potential drug-excipient interactions and incompatibilities.
• Dispense medication according to oldest stock first principle.
• Inspect medications for signs of instability.
• Ensure appropriate storage conditions are maintained.
• Repackage medications with appropriate Beyond Use Dates.
• Dispense in suitable containers with proper closures.
• Instruct patients on proper storage conditions.

Key Points Regarding Repackaging or Compounding:

• The shelf life of repackaged or compounded drugs is shorter than the original product's shelf life.
• Examples of repackaged products with reduced shelf life:
  • Eye drops (1-month use after opening)
  • Sterile tablets and capsules compounded into suspensions
  • Sterile products repackaged into single-use syringes

Understanding Drug Instability Mechanisms

• Pharmacists' roles:
  • Delay or prevent drug instability to maximize shelf life.
  • Understand reasons for drug instability to determine expiration dates and provide patient consultation.
• Drug instability mechanisms are covered in detail in later lectures.

Physical Instability

• Polymorphism transformation: The structure of a drug can change between amorphous and crystalline forms, affecting solubility and stability.
  • Crystalline structures are generally less soluble than amorphous forms, leading to a change in drug bioavailability and therapeutic effect.
  • This transformation can occur during manufacturing, due to heat, pressure and humidity, or during storage.
  • It is not visually identifiable.
• Pseudopolymorphism: Crystalline water is lost from a drug's crystalline structure, leading to a hydrated form becoming anhydrous.
  • This change can impact a drug's solubility and stability.
  • Anhydrous forms typically dissolve better than hydrated forms.
  • Examples: Carbamezepine can lose water during storage and may display tablet whiskers - lines developing on the tablet.
  • It can be prevented by adding polymers like Pluronic (used in gel formation) to the drug formulation.
• Vaporization: Loss of volatile materials, such as drugs with high vapor pressure (e.g., Trinitroglycerin, flavorings) due to evaporation.
  • Can lead to a loss of content uniformity within a batch of tablets, as evaporation can condense back onto tablets unevenly.
  • Can be prevented by using tightly sealed containers or including water-soluble polymers like polyethylene oxide, polyvinyl pyrrolidone, or microcrystalline cellulose in the formulation.
• Aging: Physical interactions that can occur over time, affecting a drug's release profile.
  • Example: Aminophylline suppositories can interact with the base, increasing the melting point and delaying drug release.
• Drug-Packaging Interaction: Drugs can interact with packing materials like PVC, leading to their absorption.
  • API absorption causes a loss of drug strength.
  • Preservative absorption can lead to microbial growth within the product.
• Precipitation: Can occur in solutions due to:
  • Changes in pH caused by other ingredients or container leaching alkaline metals.
  • Loss of cosolvent (e.g., ethanol in acetaminophen syrup).
  • Complexation with other ingredients.
  • Addition of electrolytes (salting out effect).
  • Sometimes, precipitation occurs without a clear cause and needs experience-based approaches.
  • Example: Topotecan (anti-cancer drug) solubility is affected by concentration, diluent, and container material.
• Mentimeter Questions
  • Polymorphism: The correct answer is Drug Solubility and Bioavailability.
  • Pseudo Polymorphism: The correct answers are Physical Instability and Therapeutic Instability.