Uf Dosage Forms Test 2 Mobley

Front 1

Drug product contains___ and ___

Back 1

active, inactive

Front 2

why is chemical integrity critical?

Back 2

drug must stay intact

Front 3

chemical changes to drug can change therapeutics how?

Back 3

pharmacology or kinetics can change and change how the drug goes through the body

Front 5

tetracycoine can ____ which changes the chemical properties

Back 5

epimerize

Front 6

penicillins can decompose in acidic solutions to form____

Back 6

possibly allergic compounds (degradation product)

Front 7

Pralidoxime can degrade under basic conditions to form ___ as a byproduct

Back 7

cyanide

Front 8

organoleptic properties

Back 8

susceptible to sensory impressions

Front 9

polymorphism

Back 9

crystalline structure changes

Front 10

physical property can change theurapeutics how?

Back 10

changing blood levels from dissolution changes

Front 11

physical properties can change organoleptic properties how?

Back 11

drug in solution elicits taste

Front 12

microbial invasion of a drug product is considered to be a ___ problem and does what 2 adverse things?

Back 12

stability
unappealing
deadly

Front 13

hydrolysis

Back 13

cleavage of a molecule by reaction with water

Front 14

hydrolysis of ester ex.

Back 14

aspirin

Front 15

hydrolysis of lactam ex.

Back 15

penicillin (eg ampicillin), cephalosporins

Front 16

hydrolysis of lactone ex.

Back 16

spironolactone

Front 17

lactam is a____ and lactone is a ____

Back 17

cyclic amide
cyclic ester

Front 18

autoxidation is _____, ____ is not very reactive

Back 18

slow, oxygen

Front 19

reactive oxygen species (3)

Back 19

superoxide, hydrogen peroxide, hydroxyl radical

Front 20

what can metal catalysts help with?

Back 20

reactive oxygen oxidations, they form hydroxyl radicals that are more reactive

Front 21

free radical mechanism of oxidation:
initiation

Back 21

the formation of substrate free redicals necessary for the propogation of the chain

Front 22

free radical mechanism of oxidation:
propogation

Back 22

free radicals grow in number

Front 23

free radical mechanism of oxidation:
termination

Back 23

free radicals combine to form chemically inert products

Front 24

free radical mechanism of oxidation:
initiation 1. involves ____ abstraction. 2. can occur through ___ by molecular oxygen or with other chain-initiating radicals 3. chain-initiating radicals are generated by the action of ___,___,____, or ____

Back 24

1. hydrogen
2. autooxidation
3. light, heat, transitions metals, or reactive compounds (ex peroxides)

Front 25

oxidation of catechols ex? what is the product and what is special about it?

Back 25

catecholamines, epinephrine
quinone, generally colored

Front 26

oxidation of thiol ex?

Back 26

captopril

Front 27

polyunsaturated hydrocarbons have ____, ex of oxidation of these are?

Back 27

conjugated DB with high E electrons, lipids, Vitamin A

Front 28

photolysis is:

Back 28

chemical breakdown caused by light; usually by complex mechanisms

Front 29

a photon with a wavelength of 300 nm has 400 kJ/mol of E, which is comparable to the ____ of organic molecules

Back 29

bond energy, thus can help break or make bonds

Front 30

different molecules have susceptibilities to different types of light (___ vs ___) based on their absorption characteristics

Back 30

fluorescent, incadescent

Front 31

photooxidation is the most common ____ mechanism, other photodegradations include _____

Back 31

photolytic
certain hydrolysis and dehydration reactions

Front 32

___ light is more engergetic, and these pills are ____ (color)

Back 32

UV
white

Front 33

dehydration

Back 33

elimination of water from the chemical structure

Front 34

dehydration examples (2)

Back 34

1. tetracycline
2. erythromycin--occurs under acidic conditions to yield a less active product

Front 35

physical degradation of a drug ex?

Back 35

removal of water from a crystal hydrate

Front 36

physical dehydration can change solubility (t/f)

Back 36

true

Front 37

All trans Vit A is more active than if cis forms are present (t/f)

Back 37

true

Front 38

stereoisomerization involving the arrangement of substituents about an asymmetric C atom or atoms so that the various isomers differ in how they rotate a plane of polarized light

Back 38

optical isomer

Front 39

isomerization affects ____, ____, pilocarpine, epineprhine, and vitamin A

Back 39

tetracycline, amphotericin B

Front 40

cis-trans isomerization is also known as ____

Back 40

geometric isomerization

Front 41

one of a pair of molecular entities which are mirror images of each other and non-superimposible

Back 41

enantiomers

Front 42

how do entantiomers differ in biological properties?

Back 42

different metabolism or receptor interaction

Front 43

what physiochemical properties can differ in geometric isomers?

Back 43

solubility, stability, and compatibility

Front 44

two or more drug molecules combine to form a complex molecule

Back 44

polymerization

Front 45

examples (2) of polymerization of drugs?

Back 45

chlorpromazine, concentrated solutions of aminopenicillins (ampicillin)

Front 46

__ and ___ can form dimers, which are thought to be allergenic

Back 46

ampicillin, amoxicillin

Front 47

Drugs marketed as a pure entantiomer may ____ (on shelf or in vivo), example is ____, where one isomer is very teratorginic, process is ____ catalyzed

Back 47

racemize
thalidomide
base

Front 48

physical degradation is a change in ____ rather than chemical structure

Back 48

physical properties

Front 49

internal structure determines the crystal ____, which is a description of the outer appearance of a crystal

Back 49

habit

Front 50

different habits can result from minor changes in ____

Back 50

synthetic conditions

Front 51

ex. of drug that has habit changes, and what does this affect?

Back 51

carbamazepine
flow

Front 52

flow properties are important for ___

Back 52

dosage uniformity

Front 53

bioavailability is the fraction of an administered dose that reaches ___, and is a function of drug dissolution that changes with ___

Back 53

systemic circulation
different forms

Front 54

melting point is a function of ___

Back 54

strength of molecular interactions

Front 55

uptake of atmospheric water into a solid

Back 55

hygroscopicity

Front 56

The form of a solid drug may affect its:
(5 things)

Back 56

1. flow properties
2. mechanical properties
3. bioavailability
4. MP
5. Solid state stability

Front 57

what is an ex of mechanical property being affected by solid form?

Back 57

compaction of tablets so they don't fall apart

Front 58

what are the properties of a drug that are relevant to stability? (3)

Back 58

1. chemical
2. physical
3. microbiological

Front 59

chemical degradation mechanisms (6)

Back 59

1. hydrolysis
2. oxidation
3. photolysis
4. dehydration
5. isomerization
6. polymerization

Front 60

physical property changes can affect (2)

Back 60

1. therapeutics
2. organoleptic properties

Front 61

chemical property changes can affect (3)

Back 61

1. therapeutics
2. toxicity
3. organoleptic properties

Front 62

3 steps of free radical mechanism of oxidation

Back 62

1. initiation
2. propagation
3. termination

Front 63

2 ways of dehydration of a drug

Back 63

1. chemical
2. physical

Front 64

2 types of isomers

Back 64

1. geometric
2. optical

Front 65

4 physical degradation mechanisms

Back 65

1. polymorphism
2. water sorption/hygroscopicity
3. vaporization
4. adsorption to containers

Front 66

Metastable polymorphs are generally (more/less) soluble than their more stable counterparts. ex.? which polymorph is most soluble?

Back 66

more
chloramphenicol
B

Front 67

in a polymorph, molecules with weaker interactions are ___, and may change over time to a more ___ form

Back 67

metastable
stable

Front 68

being in an unstable and transient but relatively long-lived state of a chemical or physical system

Back 68

metastable

Front 69

polymorph can interconvert to different forms during (5 things)

Back 69

processing
grinding
drying
exposure to high humidity
on shelf

Front 70

ex of drug that when crystals are found it can lead to an amorphous form

Back 70

digoxin

Front 71

ex. of drug with eight potential polymorphs that may interconvert in suspension and may cause some suspended drug to dissolve

Back 71

cortisone acetate crystals suspension

Front 72

a drug that crystallizes as a combo of pure drug and solvent of crystallization is called a ___. These are called ____ (ex where water is part of the crystal lattice is a ____). The ratio of water to drug is __

Back 72

pseudopolymorphism
solvates
hydrate
1:1

Front 73

Solvates can be physically unstable under certain conditions (t/f)

Back 73

true

Front 74

the release of water of hydration from a crystal structure

Back 74

efflorescence

Front 75

some hydrates can lose water-of-hydration during handling (t/f)

Back 75

true

Front 76

efflorescence leads to problems similar to ____ problems

Back 76

hygroscopicity (water soprtion)

Front 77

some drugs can be ____ unstable when hydration water comes to the surface after grinding, which is an example of a __change leading to a __ change

Back 77

chemically
physical
chemical

Front 78

hydrates are generally (more/less) soluble than their anhydrous counterparts

Back 78

less

Front 79

experiment with anhydrous vs trihydrate cystals of ampicillin showed that anydrous form had better ___ and ___

Back 79

dissolution
bioavailability

Front 80

the tendency of a substance to take up atmospheric moisture

Back 80

hygroscopicity

Front 81

what is a problem of hygroscopicity?

Back 81

1. manufacture and handling (drugs become sticky and can't flow through the machine)
2. solid drug dissolution
3. chemical stability

Front 82

(2) affects of water soption/hygroscopicity of a drug?
(1) way to test this

Back 82

1. drug manufacture and handling
2. chemical stability in surface water
1. preformulation studies include "stressing" the solid by storing at high humidity

Front 83

Increased cohesiveness of a drug (that can happen with water soprtion/hygroscopicity) can lead to (2)

Back 83

1. poor flow and mixing of powders
2. "caking" of powders

Front 84

where particles become united

Back 84

caking

Front 85

the dissolution of a solid upon uptake of atmospheric moisture

Back 85

deliquescence

Front 86

drugs are generally less chemically stable in the solid state (t/f)

Back 86

false, more stable

Front 87

the uptake of water by the solid drug can accelerate the drug's chemical degradation, ex. is ___

Back 87

aspirin, forms acetic acid and salicylic acid

Front 88

why would you stress a solid drug at high humidity?

Back 88

to get faster info on hygroscopicity

Front 89

What drug has strict storage requirements because it can pass out of the container?

Back 89

nitroglycerin

Front 90

drugs and excipients with high VP may volatize through or within the container, examples are (3)

Back 90

1. flavorants
2. cosolvents
3. nitroglycerin

Front 91

Certain drugs, especially when in soln, can adsorb to their container or other devices they come in contact with, examples are (3) and happen with an interaction of ___ and ____ due to ____

Back 91

1. diazepam
2. insulin
3. isosorbide dinitrate
drug/plastic (in IV admixtures)
partitioning in plastic

Front 92

Rate processes are fundamental for pharmaceutics. In Preformulation/formulation for (3)

Back 92

1. stability
2. incompatibility
3. dissolution

Front 93

Rate processes are fundamental for pharmaceutics. In biopharmaceutics for (4)

Back 93

1. absorption
2. distribution
3. elimination
4. pharmacokinetics

Front 94

instantaneous rate: rate= +/- ____

Back 94

dC/dT (change in [] at time t)

Front 95

aA + bB .....
reaction rate is k [A^a][B^b]
what do these variables mean?

Back 95

k = proportionality constant of a + b called the rate constant of the reaction at at particular temp
A = molar [] of A
a = number of mole equivalents of A

Front 96

overall order of the reaction is the sum of the ____

Back 96

exponents

Front 97

first order degradation, rate is proportional to ___. Decay is ____

Back 97

[ ]
exponential

Front 98

how would you calculate concentration above first-order degradation? Graph is ___ on y and ___ on x. slope is ___

Back 98

ln C = ln Co - k1t
ln C
t
-k1

Front 99

shelf-life is usually the time for ___ degradation and is denoted as ___. exception is____ and degradation is ____.

Back 99

10%
t90
tetracycline
3%

Front 100

pH can affect degradation rates by __ and ___ catalysis (how for each)?

Back 100

acid (protonation of the carboynyl oxygen makes the c more electrophylic)
base (hydroxyl ion is very nucleophilic)

Front 101

The pH of maximum stability (in graph log k is y and pH is x) is the point where k is the ____, and this is the only concern (t/f)

Back 101

lowest
false, solubility and patient comfort have to be considered

Front 102

typical a 10 degrees rise in temp produces a ___ fold decay rate increase

Back 102

2-5

Front 103

the effect of temperate on degradation rates is given by the ___ equation

Back 103

Arrhenius

Front 104

what equation is used to predict shelf-life?

Back 104

Arrhenius equation

Front 105

k=Ae^(Ea/RT)
what does each stand for?

Back 105

k= rxn rate constant
A= frequency factor constant (indicates how many collisions have the right orientation to lead to the products)
Ea=E of activation
R=gas constant
T=Abs temp in K

Front 106

when converted to its log form, the arrhenius equation is useful for ___, which ____

Back 106

accelerated stability studies, predict shelf-life under normal storage conditions

Front 107

when plotting concentration vs time on a graph, the ___ line will have the highest temperature

Back 107

lowest

Front 108

In a graph of LnC vs time, the rate constant can be calculated from the ___, then to get Ea, you can take the log of the calculated rate constant and plot against the recipricol of the absolute temp

Back 108

slope

Front 109

(2) examples of where non-Arrhenius behavior would occur

Back 109

1. temp changes lead to solvent evaporation, multiple reaction pathways, or change in physical form of the preparation
2. freezing the product concentrates the solutes, with untoward consequences

Front 110

(2) Ex of freezing the product concentrates the solutes where non-Arrhenius behavior would occur

Back 110

1. ampicillin forms pockets of high [] thus increased degradation rate
2. frozen buffers crystallize and can alter pH, ex. phosphate buffers

Front 111

accelerated stability studies do not have to be performed in the final formulation in the final storage container (t/f)

Back 111

false, they must be because both can affect stability

Front 112

Though tentative expiration dates can be assigned using accelerated stability studies, there must be long term studies under normal transport and storage conditions (t/f)

Back 112

true, to verify and maybe extend the expiration date

Front 113

If the expiration date includes only the month and year, the product must meet specifications until the last day of the month (t/f)

Back 113

true

Front 114

For solid dosage forms, samples are generally stressed by storing at 40 degrees C at high humidities (ex. 70%) for 6 to 12 months to rapidly determine the effect of water sorption (t/f)

Back 114

t

Front 115

problems with storing drugs at reduced temps (2)

Back 115

1. potential probs with freezing
2. potential for water condensation

Front 116

General approaches for maintaining drug stability (7)

Back 116

1. store at reduced temps
2. buffer the product appropriately
3. dry the product (with dessicants or lyophilization)
4. remove/replace O2
5. use antioxidants
6. Minimize metal content with chelators
7. protect from light

Front 117

drugs are nearly always more stable in the solid state than in aqueous soln (t/f)

Back 117

t

Front 118

ex of desiccant

Back 118

silica gel to absorb moisture

Front 119

to make "solvent-loving" by freeze-drying

Back 119

lyophilization

Front 120

Steps in lyophylization (3)

Back 120

1. starts with a liquid that includes drug plus excipients (ex. sugars to add bulk)
2. samples are frozen then sublimed under vacuum (overnight)
3. a porous matrix usually results (pores remain where water crystals were)

Front 121

(2) ways to remove/replace O2

Back 121

1. distill, then purge the water with an inert gas
2. Fill the container headspace with an inert gas such as nitrogen or argon

Front 122

two types of antioxidants, exs of each

Back 122

1. oil-soluble: alpha-tocopherol (Vitamin E), buylated hydroxytoluene (BHT)
2. water-soluble: ascorbic acid (Vitamin C), sodium sulfite

Front 123

___ is a common allergen in 0.2% of the population

Back 123

sulfites

Front 124

Two principle mechanisms of antioxidant action:

Back 124

1. stop propagation (chain terminators, free-radical scavengers)
2. preferentially oxidized (more easily oxidized)

Front 125

Source of metals that get into drugs

Back 125

trace amounts in chemicals and containers

Front 126

ex of chelator:

Back 126

citric acid

Front 127

For oral and topical products, no more than 10% of the light at any wavelength b/w 290 nm and 450 nm may be transmitted (t/f)

Back 127

t

Front 128

The lower the wavelength, the (higher/lower) the E

Back 128

higher

Front 129

High E is absorbed by (few/most) drugs

Back 129

most

Front 130

fluorescent light includes some ___ light, and extra caution should be taken (t/f)

Back 130

UV
true

Front 131

order of light types from lowers wavelength to highest wavelength

Back 131

1. UV
2. Sunlight
3. Fluorescent
4. Visible
5. Incandescent

Front 132

What can be done to protect a drug from light?

Back 132

use an amber container, it excludes most UV light if thick enough

Front 133

Responsibilities of the pharmacist for keeping drugs stored properly (5)

Back 133

1. Rotate stock and observe expiration dates
2. Storage under recommended environmental conditions
3. Observing products for evidence of instability
4. Proper treatment of products subject to additional manipulation
5. Informing and educating the patient

Front 134

If a pharmacist changes a product, they are then responsible for stability (t/f)

Back 134

true

Front 135

Expiration dates are valid only when the products are stored properly (t/f)

Back 135

true

Front 136

Pharmacists must observe and record any changes in products (t/f)

Back 136

true