Stability Flashcards
Accelerated Stability
-speed up process of degradation
-use higher temps of aq solutions
a SOLUTION drug will be stable only
-at given concentration
-certain time
-certain temp
-certain light exposure
a SOLID drug will be stable only
-certain time
-certain temp
-certain light exposure
do solutions or solids decompose faster?
solutions
Hydrolysis
-water cleaves molecule
-reacts and degrades drugs
-slide 3
Rate of hydrolysis
-DEcreaases as pH INCREASES
Oxidation
-catalyzed by copper
-use oxygen from atmosphere
-OH to =O
-browning onions
-store some drugs under nitrogen!
Oxidation of vitamin C
ascorbic acid + copper =dehydroacorbic acid
-makes -O to =O
-slide 12
Compatibility issues
-problem for long infusion times with piperacillin/tazobactam extended fusions
-NOT in shorter infusion times tho
Compatibility issues with longer infusions can occur with:
-other antibiotics (azithromycin, ciprofloxacin, tobramycin)
-insulin
-some vasopressors
Long infusion time
amount of time for IV to deliver drug
High temperature effect on stability
-speed up degradation
IV drug storage
-most refrigerated
-some room temperature
Furosemide and phenytoin
-crystalize if kept cold
=less bioavailability
Light exposure
-photodegradation
-may increase toxicity
-amber vials for protection
-change in color/appearance
Light sensitive drugs
-Vitamin K
-Nitroprusside
-Doxycycline
-must be protected from light during administration
Stability
the extent to which a product retains same properties and characteristics during shelf-life
Chemical Reactions that Cause drug Degradation
-oxidation
-hydrolysis
-photolysis
Oxidation of epinephrine
-OH oxidized to =O
Oxidation examples
-vitamin C
-epinephrine
-browning onions
Prevention of oxidation
-NO temp change
-buffers for pH
-light protection
-or lower temp to slow
-chelating agents
-antioxidants
chelating agents
-EDTA
-remove metal ions that can cause oxidation
antioxidants
remove free radicals produced by oxidation
Compounds likely to be hydrolyzed
-carbonyl
-amide
Hydrolysis prevention
-remove moisture with absorbants
-lyophilization (freeze-drying)
-non-hygroscopic salt (dont absorb water like other solids)
-control TEMP and PH
Photolysis
-drug sensitive to light
-vitamin C
-nitroprusside
-phytonadione injection
Other processes that degrade drugs
-isomerization
-epimerization
-decarboxylation
Isomerization
compound changes into form with same atoms but inactive structure = cant fit
epimerization
-change to isomer with diff chirality
-active or inactive
Decarboxylation
-carboxylic acid lose CO2
-can be avoided by refrigeration
function of dosage form
-right dose
-promote dissolution
-delivery to site of action
-ensure drug stability
-dosing interval
Hydrolysis of esters and lactones
-nucleophillic attack
-MIGHT just need to know intermediate
hydrolysis of carboxylic acid ester
-RCOOR
-produces carboxylic acid and alcohol
Hydrolysis mechanism in BASIC conditions
- free OH- attacks carbon
- move double bond electrons to O
(tetrahedral intermediate)
3.move electrons back down to kick out OR ESTER group - carboxylic acid with negative oxygen + OR-
- OR- takes H of carboxylic acid
- carboxylate
Hydrolysis mechanism in BASIC conditions
- carboxylic acid protonated
- water attacks carbon
(tetrahedral intermediate)
3.
Aspirin Hydrolysis
-produces salicylic acid and acetic acid
-old bottles smell like vinegar
-acetylation of COX prevents stroke
Open an aspirin bottle what do you smell
VINegar
Lactone hydrolysis
-cyclic esters
-opens ring = hydroxy acid
GBL hydrolysis (lactone)
-opens five-membered ring
-converted to GHB in the body
GBL
-lactone
-inactive
-prodrug for GBH
-absorbed more rapidly
