Drug Stability, Expiry & Disposal (Updated)

Drug Stability

Learning Objectives

  • Upon completion of this section, students should be able to:
    • List and explain the different types of drug stability.
    • List and explain the different types of drug instability.
    • Differentiate between a drug’s expiration date and beyond use date.
    • Determine beyond use dates for compounded non-sterile products and repackaged unit doses according to USP 795.
    • Understand the purpose of Ontario Medications Return Program (OMRP) and the Ontario Sharps Collection Program (OSCP) and the responsibility of a pharmacy technician in drug disposal.

Drug Stability

  • A drug is considered stable when a dosage form retains its stability under specified limits:
    • Throughout its period of storage.
    • Throughout its period of use.
    • Retains the same properties and characteristics that it possessed at the time of manufacture:
    1. Identity
    2. Quantity
    3. Strength
    4. Quality
    5. Purity
    6. Appearance
    7. No toxic products formed (USP

Stability Aspects

  • Stability must occur in the following:
    • Active Drug (Active Ingredient): Must maintain the same quantity, form, and bioavailability as indicated on the label with no chemical change nor toxic products produced.
    • Entire Drug Product When Used Alone:
    • For example, clear solutions must remain clear and suspensions must remain suspended.
    • Entire Drug Product When Mixed:
    • No incompatibilities (instabilities) when mixed with other products.

Types of Stability

  • Types of Drug Stability:
    • Physical Stability: Physical properties do not change.
    • Chemical Stability: Retains chemical integrity and potency (as labeled).
    • Microbiological Stability: Retains sterility or resistance to microbial growth.
    • Therapeutic Stability: Therapeutic effect remains.
    • Toxicological Stability: No significant increase in toxicity.
    • These types usually assured if physical, chemical & microbiological stabilities achieved.

Types of Drug Instability

  • Types of Instability:
    • Visible Instability: Instabilities that can be seen with the naked eye.
    • Invisible Instability: Instabilities that cannot be seen.
  • Rate of Change or Development of Instability:
    • How quickly instability develops and under what conditions.

Types of Instability Explained

  • Physical Instability:

    • Visible Examples:
    • Precipitation (particles appear in a solution).
    • Caking of a suspension.
    • Cracking of an emulsion (separate oil and water layers appear).
    • Invisible Examples:
    • Complex formation between drug and an ion in solution, leading to drug becoming biounavailable.
    • Drug adsorbing to the container.

  • Chemical Instability:

    • Visible Changes:
    • Color change.
    • Gas formation.
    • Change in smell.
    • Precipitate formation.
    • Invisible Changes:
    • Hydrolysis.
    • Oxidation.
    • Photolysis.
    • Changes in pH and temperature affecting stability.

Hydrolysis

  • Definition:
    • Hydro = water + Lysis = splitting. Drug molecules interact with water molecules, leading to breakdown or reaction products (e.g. ASA + H2O → salicylic acid + acetic acid).
  • Prevention Methods:
    • Eliminate water from formulation (use non-aqueous vehicle e.g., glycerin, ethanol, propylene glycol).
    • Supply drug in dry powder form and reconstitute at dispensing.
    • Protective coating for drug or dosage form.
    • Add a desiccant (moisture absorber) to drug container.
    • Use moisture-resistant packaging (e.g., tightly closed glass container).
    • Slow rate of hydrolysis by storing in a refrigerator.
    • Control pH with buffers (for most drugs at pH 5-6, slow rate of hydrolysis).

Oxidation

  • Definition:
    • Loss of electrons by one molecule while transfers/gains occur to another.
    • Often involves 'Free radicals' that self-propagate and increase the rate of oxidation.
  • Factors Increasing Oxidation:
    • Trace metals (Cu, Fe).
    • Free radicals.
    • Light.
    • Non-optimal pH.
    • Heat and moisture.
  • Prevention Methods:
    • Use of chelating agents.
    • Antioxidants or inert gas replacement for oxygen.
    • Light protective coatings (amber containers).
    • Store at cool temperatures.
    • Dry powder formulation.

Photolysis

  • Definition:
    • Photo = normal room or sunlight + Lysis = splitting. Drug molecules absorb different wavelengths of light and decompose, which may catalyze oxidation reactions.
  • Prevention Methods:
    • Package light-sensitive drugs in light-resistant or opaque containers.
    • Care when repackaging the drug.

pH Stability

  • Changes in pH can occur when:
    • Solution is diluted.
    • Another chemical is added.
    • Change in packaging container.
    • Change in storage temperature.
  • Effects of pH Changes:
    • Affect solubility of drug or excipients.
    • Increase rates of chemical degradation.
  • Maintaining Optimal pH:
    • Use buffers to achieve and maintain optimal pH.
    • Caution when changing the vehicle, container, or storage conditions.

Temperature Effects

  • Temperature influences chemical stability:
    • Rate of hydrolysis.
    • Rate of oxidation.
  • Optimal Temperature Requirements:
    • Specific drugs like vaccines may require tight temperature control during storage, transportation, and use.

Important Temperature Ranges

  • Storage Temperatures:
    • Cold: Below 8°C (Refrigerator RF: 2-8 °C).
    • Cool: 8-15 °C.
    • Controlled Room Temperature: 15-30 °C.
    • Warm: 30-40 °C.
    • Excessive Heat: Above 40 °C.

Microbial Stability

  • To avoid microbial contamination during:
    • Manufacturing.
    • Dispensing.
    • Repackaging.
    • Administration.
    • Use.
  • Methods to Avoid Microbial Contamination:
    • Aseptic or clean procedures during all stages mentioned above.
    • Use of antibacterial and antifungal preservatives in drug products.

Knowledge Checks

  • Fill in the blanks and answer questions related to drug stability, types of instability, hydrolysis prevention, storage temperature requirements, and definitions of beyond use dates.

Drug Expiry & Disposal

  • Expiration Date:

    • Date beyond which ideally stored medications in an unopened manufacturer’s storage container or even in an opened and intact manufacturer’s container should not be used.
    • During this time, drugs are expected to meet the requirements of the pharmacopeia monograph provided they are kept under the prescribed conditions.
    • Drugs are considered potent and safe during this period, typically 2-3 years from the date of manufacture as stated on the product label.

  • Beyond-Use Date (BUD):

    • Date beyond which medications that have been manipulated or repackaged should not be used.
    • Examples include reconstituted antibiotics, drugs repacked into unit-dose containers, and injectable drugs that have been reconstituted or diluted prior to administration.
    • BUD determines how long after reconstitution or compounding a drug remains stable.

Beyond-Use Date Regulations & Guidelines

  • Beyond-use date should be conservative based on guidance from USP
  • BUD General Guidelines (if specific info is unavailable):
    • Non-aqueous formulations: 6 months (180 days) or the time remaining until the earliest expiry date of any active pharmaceutical ingredient (API), whichever is earlier.
    • Water-containing oral formulations: 14 days if stored at controlled cold temperatures.
    • Water-containing topical/dermal or mucosal liquid/semi-solid formulations: 30 days.

Unit-Dose Repackaging and BUD

  • Unit-Dose Repackaging (USP
    • Repackaging involves removing a preparation from its original primary container and placing it into another primary container, usually smaller in size.
    • When repackaging tablets or capsules into unit-dose containers, use stability data in the repackaged container if available.
    • Beyond-use date for unit-dose repackaging: 1 year or time remaining to expiration date, whichever is shorter.

Drug Disposal in a Pharmacy

  • Protects:
    • The patient.
    • Family and friends.
    • The handler (healthcare & support staff).
    • The environment.
  • Follow and participate in the development of policies and procedures established in the pharmacy & institution for:
    • Drugs.
    • Containers.
    • Supplies.

Prevent Medication Accidents

  1. Store medications out of sight and reach of: children, teens, visitors, and pets.
  2. Place unused medications in a bag and return to pharmacy.
  3. For locations accepting returns, contact health steward or local pharmacy.

Ontario Medications Return Program (OMRP)

  • Purpose:

    • To recover as much of targeted materials as possible to prevent them from ending up in landfills or waterways.
    • Pharmaceuticals in waterways pose a hazard to human and animal health (e.g., hormones, antibiotics).

  • Covers the costs of disposal for these returned health products:

    • All prescription drugs, over-the-counter medications, and natural health products in oral dosage form (including opioid patches).

Ontario Sharps Collection Program (OSCP)

  • Purpose:
    • Promotes safe and easy disposal of sharps returned by the public.
    • Covers disposal costs to prevent hazardous disposal in regular garbage.
  • What are sharps? Examples include infusion sets, safety pens and syringes with needles, lancets, needle tips, pre-filled cartridges, and pre-filled syringes.

Process for Drug Disposal by Consumers

  • Where to return: Any participating pharmacy in the community.
  • Precautions: Store securely, dry, and out of reach of children and pets.
  • Post-return: Collected pharmaceuticals are safely incinerated by HPSA-approved waste management companies in accordance with regulatory requirements.

Knowledge Check Questions

  • Several knowledge checks related to evaluations of stability, understanding of expiration and BUD differences, and the handling of expired or unused medications are provided throughout the material.

Conclusion

  • Responsibilities of pharmacy staff concerning drug disposal and regulations are critical to ensure safety for all stakeholders involved in drug handling and storage.