Degradation and Stability Lecture Flashcards
Define stability
Extent to which a product retains, within specified limits, and throughout its period of storage and use, the same properties and characteristics that is possessed at the time of its manufacture
What does GMP state?
There must be a written testing program designed to assess stability characteristics of drugs
- Results determine appropriate storage conditions and expiration dating
What does time-related harmful events include?
Deterioration of therapeutic activity below specified threshold
Potentiation of therapeutic activity above specified threshold
Appearance of toxic substance forming as a degradation by-product
What are factors that affect stability of a pharmaceutical product?
Stability of active ingredient
Interaction between active/inactive ingredients
Manufacturing process
Dosage formulation
Container/liner/Closure system
Environment
Length of time between manufacturing and usage
What are chemical routes of degradation?
Hydrolysis or solvolysis Oxidation Photolysis Dehydration Isomerizaiton Hydration Decarboxylation Pyrolysis Incompatibilities
What are physical routes of degradation?
Polymorphism Vaporization Aging Adsorption Liquefaction
When a physical change occurs, the same drug or chemical is still present, but its physical state is alter means?
Drug precipitate out of solution
Drug adsorbing to the walls of the polyvinyl chloride container
Two solid drugs forming a liquid eutectic mixture during trituration
Changing in physical appearance means?
Mottling of tablets, creaming of emulsions, caking of suspensions
-Therapeutic efficacy of the dosage form may be unaffected by these changes, but the patient will lose confidence in the product
Define aging
Changes in the disintegration or dissolution characteristics of the dosage form are caused by subtle and sometimes unexplained. alterations in the physicochemical properties of the inert ingredients or the active drug int the dosage form or simply appearances of the dosage form
Define polymorphism
The degree of crystallinity can also affect the appearance, bioavailability, and chemical stability of pharmaceuticals
Example of polymorphism
More soluble crystal form (form II) of cortisone acetate converts to a less soluble form (form V) when the drug is formulated into an aqueous suspension (leads to caking of the cortisone acetate suspension)
- Cystalline insulin and cyclophosphamide are much more stable than their amorphous counterparts
Define efflorescent powder
Contain water of hydration that may be released when powders are triturated or when stored (dumpy or pasty powder)
Define vaoprization
High vapor pressures at room temperature that results in loss of drug quantity due to volatilizaiton through the container
Example of vaporization
Nitroglycerin: when conventional (unstabilized) nitroglycerin sublingual tablets are stored in enclosed glass containers –> redistribution among tablets
- Deterioration in the uniformity of the tablets during storage
Define adsorption
The surface of a solid hold molecules of other substances that come in contact with it (surface phenomenon)
Drug-plastic interaction occurs when intravenous solutions are stored in bags, or when they are infused through administration sets that are made from PVC
