Stability

Question 1

Accelerated Stability

Answer 1

-speed up process of degradation
-use higher temps of aq solutions

Question 2

a SOLUTION drug will be stable only

Answer 2

-at given concentration
-certain time
-certain temp
-certain light exposure

Question 3

a SOLID drug will be stable only

Answer 3

-certain time
-certain temp
-certain light exposure

Question 4

do solutions or solids decompose faster?

Answer 4

solutions

Question 5

Hydrolysis

Answer 5

-water cleaves molecule
-reacts and degrades drugs
-slide 3

Question 6

Rate of hydrolysis

Answer 6

-DEcreaases as pH INCREASES

Question 7

Oxidation

Answer 7

-catalyzed by copper
-use oxygen from atmosphere
-OH to =O
-browning onions
-store some drugs under nitrogen!

Question 8

Oxidation of vitamin C

Answer 8

ascorbic acid + copper =dehydroacorbic acid
-makes -O to =O
-slide 12

Question 9

Compatibility issues

Answer 9

-problem for long infusion times with piperacillin/tazobactam extended fusions
-NOT in shorter infusion times tho

Question 10

Compatibility issues with longer infusions can occur with:

Answer 10

-other antibiotics (azithromycin, ciprofloxacin, tobramycin)
-insulin
-some vasopressors

Question 11

Long infusion time

Answer 11

amount of time for IV to deliver drug

Question 12

High temperature effect on stability

Answer 12

-speed up degradation

Question 13

IV drug storage

Answer 13

-most refrigerated
-some room temperature

Question 14

Furosemide and phenytoin

Answer 14

-crystalize if kept cold
=less bioavailability

Question 15

Light exposure

Answer 15

-photodegradation
-may increase toxicity
-amber vials for protection
-change in color/appearance

Question 16

Light sensitive drugs

Answer 16

-Vitamin K
-Nitroprusside
-Doxycycline

-must be protected from light during administration

Question 17

Stability

Answer 17

the extent to which a product retains same properties and characteristics during shelf-life

Question 18

Chemical Reactions that Cause drug Degradation

Answer 18

-oxidation
-hydrolysis
-photolysis

Question 19

Oxidation of epinephrine

Answer 19

-OH oxidized to =O

Question 20

Oxidation examples

Answer 20

-vitamin C
-epinephrine
-browning onions

Question 21

Prevention of oxidation

Answer 21

-NO temp change
-buffers for pH
-light protection
-or lower temp to slow
-chelating agents
-antioxidants

Question 22

chelating agents

Answer 22

-EDTA
-remove metal ions that can cause oxidation

Question 23

antioxidants

Answer 23

remove free radicals produced by oxidation

Question 24

Compounds likely to be hydrolyzed

Answer 24

-carbonyl
-amide

Question 25

Hydrolysis prevention

Answer 25

-remove moisture with absorbants -lyophilization (freeze-drying) -non-hygroscopic salt (dont absorb water like other solids) -control TEMP and PH

Question 26

Photolysis

Answer 26

-drug sensitive to light -vitamin C -nitroprusside -phytonadione injection

Question 27

Other processes that degrade drugs

Answer 27

-isomerization -epimerization -decarboxylation

Question 28

Isomerization

Answer 28

compound changes into form with same atoms but inactive structure = cant fit

Question 29

epimerization

Answer 29

-change to isomer with diff chirality -active or inactive

Question 30

Decarboxylation

Answer 30

-carboxylic acid lose CO2 -can be avoided by refrigeration

Question 31

function of dosage form

Answer 31

-right dose -promote dissolution -delivery to site of action -ensure drug stability -dosing interval

Question 32

Hydrolysis of esters and lactones

Answer 32

-nucleophillic attack -MIGHT just need to know intermediate

Question 33

hydrolysis of carboxylic acid ester

Answer 33

-RCOOR -produces carboxylic acid and alcohol

Question 34

Hydrolysis mechanism in BASIC conditions

Answer 34

1. free OH- attacks carbon 2. move double bond electrons to O (tetrahedral intermediate) 3.move electrons back down to kick out OR ESTER group 4. carboxylic acid with negative oxygen + OR- 5. OR- takes H of carboxylic acid 6. carboxylate

Question 35

Hydrolysis mechanism in BASIC conditions

Answer 35

1. carboxylic acid protonated 2. water attacks carbon (tetrahedral intermediate) 3.

Question 36

Aspirin Hydrolysis

Answer 36

-produces salicylic acid and acetic acid -old bottles smell like vinegar -acetylation of COX prevents stroke

Question 37

Open an aspirin bottle what do you smell

Answer 37

VINegar

Question 38

Lactone hydrolysis

Answer 38

-cyclic esters -opens ring = hydroxy acid

Question 39

GBL hydrolysis (lactone)

Answer 39

-opens five-membered ring -converted to GHB in the body

Question 40

GBL

Answer 40

-lactone -inactive -prodrug for GBH -absorbed more rapidly