Exam 3 - Solutions for Injections Flashcards
(22 cards)
Explain why solution formulations are so popular
- Simplest and least expensive to manufacture
- Convenient for patients and hospital personnel because they do NOT require reconstitution (medication is ready to use/take for patients)
- Can be manually inspected visually prior to administration
List common clinical concerns for solutions
- efficacy
- sterility (not sterile forever)
- side effects (dose-limiting immune response)
- pain on injection (IM, SC)
List common formulation concerns for solutions
all clinical concerns & also…
- stability
- manufacturability (cost, time)
Explain stability formulation concerns for solutions
- Aggregation
- Chemical stability (deamidation, oxidation)
- Shelf-life
- Storage conditions (temp, etc.)
What is the ideal pH for injections for the PATEINT?
pH 7.4
What is the ideal pH for injections for the DRUG?
the lowest degradation point on a degradation rate constant vs. pH graph
usually lower than 7.4
Explain how aggregation affects the turbidity of a solution
turbidity is greater when aggregates are present
Explain how protein concentration affects the aggregation of a solution
aggregate content increases with increasing protein concentration
higher concentration = greater aggregation
List solution property variables
- pH
- Ionic strengths, tonicity
- Volume
- Excipients (additives)
List common variables in solution
- solution properties
- container, closure
- storage conditions (ex. temp)
Describe preferential binding
- leads to unfolding / denaturation
- de-stabilized
exception: protein binding to ligands can stabilize native structures
Describe preferential exclusion
- makes proteins work to bind (VIP pass)
- stabilized
- promote interactions with water
- stabilize native protein structures
What is the indication for EPO (epoetin)?
used to treat anemia in renal disease
What is the issue with EPO (epoetin)?
- Anti-EPO antibodies can be formed
- Formation of anti-EPO antibodies reduces a drug effect and that of any naturally occurring EPO that remains
What is the consequence to the issue with epoetin (EPO)?
PCRA (pure red cell anemia) → severe / sudden onset anemia → can lead to death
List options for solution formulations that do not work
- store at (recommended) refrigerated temperatures
- freeze
- freeze-dry (lyophilize) or spray dry to create a powder for reconstitution - RARE, $$$$
- re-engineer the protein molecule
- abandon drug candidate
List important points to remember about solution formulations
- Some biologics that are administered by injection are NOT via solutions, but rather through suspensions or emulsions
- Protect from light if recommended
avoid agitation - Examine vial particulates prior to administration
- Be cautious of the potential for adverse immune responses
List different ways that proteins aggregate
- Colloidal Interactions (least harmful and often reversible)
- Chemical Reaction Pathway
- Unfolding/Misfolding
Explain colloidal interactions
- one way that proteins aggregate
- least harmful & often reversible
- properly folded proteins interact with one another via weak, non-covalent forces and link together via colloidal interactions
imagine lego pieces being stuck together
Explain the chemical reaction pathway of protein aggregation
proteins undergo chemical modifications (via red dots in picture) where they interact and form covalent bonds to build larger, chemically linked aggregates
Explain unfolding/misfolding as a way that proteins aggregate
these proteins are partially unfolded, causing either:
- chemical reactions (where the red dots form again)
- or they stick together and form larger aggregates (irreversible)
Describe “partial unfolding”
hydrophobic part of the molecule is exposed to water, making big glomulates (big structures)
