5 - Epinephrine Flashcards
MOA of epinephrine
- Acts on alpha and beta receptors
- Increases BP by stimulating cardiac muscle
- Increases contractility, HR, and causes constriction of arterioles
- Relaxes bronchial SM
- Increases blood sugar
Epinephrine is rapidly degraded in the body by ______
Liver enzymes
Epinephrine uses
- Bronchospasm (anaphylactic reactions)
- Prolong anesthetics
What dosage forms is epinephrine available as?
Injection, inhalation, nasal, ophthalmic (always in a liquid medium)
What is pharmaceutical stability?
The extent to which a product retains, within specified limits, and throughout its period of storage/use, the same properties it possessed at the time of manufacture
What causes chemical instability and examples
- Degradation results from reactions between the active ingredients, excipients, and the environment
- Hydrolysis, oxidation, photolysis, dehydration
____ is the most significant problem that shelf-life is based upon
Chemical stability
Physical stability definition and examples of instability
- Changes in physical properties of the dosage form
- Transition between polymorphs, vaporization of volatile components, adsorption to packaging, “aging” of polymers, separation of suspensions/ emulsions/ creams/ ointments
What dosage forms is microbiological stability used for? How is it achieved?
- For injections, emulsions, ointments, and creams
- Achieved through complete enclosure, filtration, sterilization, additions of preservatives/antimicrobial agents
What determines microbiological stability?
Sterility or resistance to microbial growth should be maintained and additives should be effective for the duration of storage/ administration
What is therapeutic stability? What can compromise it?
- Effectiveness of an active ingredient in vivo
- Compromised by changes in chemical, physical, and microbiological stability
Toxicological stability
- Potential toxicity in vivo due to physicochemical or microbiological changes
- No significant increase in SEs/toxicity should be produced during normal storage/application period
Examples of environmental factors that can influence stability of pharmaceutical preparations
Temperature, radiation, sunlight, air (oxygen, carbon dioxide, water vapor), humidity
Characteristics of dosage forms that can influence stability of pharmaceutical preparations
Particle size, size distribution, pH, water/solvents, package materials, excipients/additives
What is accelerated stability testing?
Exposing the test preparation to a high stress scenario to detect instabilities (eg. temperature, humidity, light intensity)
What is accelerated stability testing used for?
- To predict pharmaceutical stability under normal conditions
- Allows selection of the most optimal formulation/packaging material, storage condition, and expiration date
What determines the design of accelerated stability testing and what does the testing determine?
- Product and manufacturer requirements
- Determine effects of temperature, light, air, pH, moisture, trace metals, and common excipients on the active ingredient
What temperature, humidity, and length of time should be used in testing for solid dosage forms?
- 25 or 37 C
- Relative humidity of 60% or 75%
- 30 day testing period
What environment should light-sensitive products be tested in?
Natural or artificial light sources
What temp is used to test liquids?
Higher temps of 40-90 C are needed to increase degradation
What rules should be followed in community pharmacy?
- Dispense oldest stock first and record expiration date
- Store under proper conditions
- Check for evidence of drug instability
- Properly treat/label repackaged/diluted/mixed preparations
- Dispense in proper containers
- Educate patients about storage/ administration
Signs of deterioration in solid dosage forms
- Fog
- Liquid droplets, clumping
- Presence of desiccant indicates care should be taken in dispensing to avoid humidity instability
Signs of deterioration in uncoated tablets
- Excessive powder or pieces of tablet at the bottom of bottle
- Cracks/chips
- Swelling
- Discolouration
- Fused tablets
- Crystals
Signs of deterioration in coated tablets
- Cracks
- Mottling
- Clumping
Signs of deterioration in dry powders/ granules for reconstitution
- Caking
- Discolouration
- For reconstitution – caking, fog, liquid droplets, unpleasant odour
Signs of deterioration in effervescent tablets/ granules/ powders
Swelling (due to moisture)
Signs of deterioration in hard/ soft gelatin capsules
- Change in consistency
- Hardening/ softening
Signs of deterioration in liquid dosage forms
- Microbial growth is a primary concern (discolouration, turbidity, gas formation)
- Cloudiness
- Precipitation
- Breaking of an emulsion
- Non-resuspendable caking of a suspension
Signs of deterioration in solutions/ elixirs/ syrups
- Precipitation
- Gas formation
Signs of deterioration in emulsions
Breaking (irreversible)
Signs of deterioration in suspensions
- Caked solid phase that cannot be resuspended by shaking
- Large particles
Signs of deterioration in sterile products
- Haziness
- Colour change
- Surface film
- Particulate
- Gas formation
- Damage to enclosure
Signs of deterioration in semisolid dosage forms
- Discolouration
- Changes in consistency/ odour
Signs of deterioration in creams (w/o, o/w)
- Breakage
- Crystals
- Water evaporation
- Microbial contamination
Signs of deterioration in ointments
- Change in consistency
- “Bleeding” (liquid)
- Grittiness
Signs of deterioration in supppositories
- Store in fridge
- Excessive softening/ hardening
- Oil stains on packaging
What is prediction of shelf-life based on?
- Arrhenius equation
- Effect of temp on rate constant of decomposition
- Linear correlation between rate constant (ln k) and temp (1/T)
Describe the methods for this experiment
- Epinephrine injection contains epinephrine bitartrate 10 mg/mL
- Describe any colour changes or precipitation of solids
- Filter 40 mL and seal in vials completely
- Subject to temp for 3 days
- Take HPLC-UV readings at sampling times
How can you determine epinephrine content?
(Peak of sample/ peak of standard)(1 mg/mL)
What are the results of this lab?
- Approximate shelf-life should be 23.6 days
- Degrades to quinones via oxidation and also undergoes methylation and deamination
Define shelf life
Time for an active ingredient to chemically degrade by 10% in its potency at 25 C
What needs to be done for a product to maintain satisfactory chemical stability?
Retain its chemical integrity and labelled potency
What is considered satisfactory physical stability?
Original physical characteristics in appearance, palatability, uniformity, disintegration, dissolution, and suspenability
___ is a compromising factor to solid dosage forms
Humidity
