Drug and Drug Product Stability

• Ability of a particular formulation in a specific container to remain within its physical,

  chemical, therapeutic, microbiological and toxicological specifications
• Is the time from date of manufacture of the formulation until its chemical or biologic

  activity is NLT 90% of the labeled potency
• The duration of time during which a preparation will remain physically, chemically and

  biologicall stable
• Are test performed at certain intervals of time for drug products in their intended

  packages and are stored at specific temperature, humidity, air and light exposure and

  other storage conditions
• Specific compendial requirement

  Physical appearance of the product

  Loss of activity or potency of the active ingredient

  Amont of degration of the product
• Temperature

  Moisture

  Agitation

  Method of manufacture

  FACTORS THAT AFFECT INSTABILITY

  Light

  Gravity

  Inversion ( for emulsions)
• Are used to predict product stability

  A method accepted by the FDA is that:

  3 months acceptable data at 37-20C and 75% RH can e extrapolated to a 2 year expiry date

  if two-year controlled room temperature samples are available, up to two more years could be

  added to the expiry date by storing the two-year RT samples at 37C and 75%RH for 3 months
• Is a direct application and interpretation of the knowledge gained from stability testing

  It limits the period during which a preparation may be expected to have its labeled potency,

  provided it has been stored as directed in the labelling
• Stability is the ability of a particular formulation in a specific container to remain within its physical, chemical, therapeutic, microbiological and toxicological specifications.
• Period of stability is the time from date of manufacture of the formulation until its chemical or biologic activity is NLT 90% of the labeled potency.
• Shelf-life is the duration of time during which a preparation will remain physically, chemically and biologically stable.
• Stability studies are tests performed at certain intervals of time for drug products in their intended packages and are stored at specific temperature, humidity, air and light exposure and other storage conditions.
• Stability considerations include specific compendial requirement, physical appearance of the product, loss of activity or potency of the active ingredient, amount of degradation of the product, and others.
• Factors that affect instability include temperature, moisture, agitation, method of manufacture, light, gravity, and inversion (for emulsions).
• Accelerated stability studies are used to predict product stability.
• An acceptable expiration date is a direct application and interpretation of the knowledge gained from stability testing.
• Overage is the voluntary addition of a specific excess during the manufacture of pharmaceutical forms of medicaments that are unstable by nature and difficult to stabilize, in order to maintain during the period of use an active content within the limits compatible with therapeutic requirements.
• Overages are justifiable when the labile (unstable) active ingredient cannot possibly be standardized, the overage allows an even equilibrium of the content of the AI within the acceptable limits, the overage would not present a possibility of a therapeutic overdosage if the preparation were used during the early part of the product’s shelf life, and the clinical studies show that overage is safe therapeutically.
• Types of overage include manufacturing overage to make up for the loss and stability overage to make up for the loss of potency during storage.
• Overages for vitamins are limited to NMT 30% of the labeled potency.
• Overages for antibiotics are NMT 15% for dry dosage forms, NMT 20% for fluids, and NMT 25% for ointments, suppositories, aerosols, creams and foams.