Drug Properties, Physiochemical Incompatibilities and Stability Flashcards
(136 cards)
1
Q
drug properties are physical characteristics that can alter ___
A
bioavailability
2
Q
define solubility
A
the max amount of substance that can dissolve in a given amount of solvent @ a specified temp and pressure
3
Q
what is the word used when two liquid dissolve in each other
A
miscible
4
Q
what is the word used when two liquids do not dissolve in each other?
A
immiscible
5
Q
give an example of 2 liquids that are miscible
A
water and ethanol
6
Q
give an example of 2 liquids that are not miscible
A
water and oil
7
Q
explain why aqueous solubility is important for drugs
A
b/c drugs can only be absorbed into the bloodstream in the aq (dissolved) form
8
Q
could a drug still have the desired effect if it didn’t dissolve in aq?
A
no
9
Q
what are the 2 main ways to measure solubility?
A
quantitative and qualitative
10
Q
what are the 6 factors that affect solubility?
A
- temperature
- solvent pH and solute Pka
- presence of other solutes
- chemical structure
- surface area
- melting/boiling point
11
Q
the solubility of inorganic electrolytes depends on their __ properties and their interactions between their
ions with __ through a process called __
A
crystal; water; hydration
12
Q
what needs tone overcome during hydration for ions to break free of their lattice structure and dissolve?
A
the heat of hydration needs to be high enough
13
Q
salts that increase the solubility of a drug are called
A
salt-in
14
Q
salts that decrease the solubility of a drug are called
A
salt-out
15
Q
the effects of additives on drug solubility depend on its interactions with what 3 things?
A
water, the solute (drug) and the solvent
16
Q
how can different functional groups influence solubility?
A
by affecting the molecular cohesion/interaction with water
17
Q
polar FG groups ___ (raise/lower) solubility of solute. How?
A
raise; by forming H bonds with the water
18
Q
non-polar groups ___ (raise/lower) solubility of solute
A
lower
19
Q
ionization of a FG ___ (raises/lowers) solubility
A
raises
20
Q
why does ionization of a FG raise solubility?
A
charged groups are more polar and therefor more hydrophilic and soluble in water
21
Q
list the FG position of otrtho, meta, para in order from least to most soluble in water
A
para; ortho; meta
22
Q
effect of pH is crucial to drugs with __ groups
A
ionizable
23
Q
acidic drugs are more soluble in __ solutions and less soluble in __ solutions
A
basic; acidic
24
Q
give an example of an acidic drug
A
NSAIDs
25
basic drugs are more soluble in __ solutions and less soluble in __ solutions
acidic; basic
26
why does surface area affect solubility?
b/c placing a solute molecule in the solvent requires solute-solvent contact points
27
a larger surface area means a ___ (higher/lower) solubility
higher
28
why does larger surface area result in greater solubility?
larger cavity required, more contact points made, making it easier for the solvent to dissolve the solute
29
the melting point of solids and the boiling point of liquids reflects what?
the strength of the interactions between the molecules in the compound
30
As melting and boiling points increase, what happens to solubility?
decreases
31
drug partition between 2 immiscible solvents is based on __ solubility
affinity
32
the partition coefficient (logP) measures what?
the spreading of solute between the aq and organs phases of an immiscible mixture
33
the P in the partition coefficient is represented by the rate of ___ over __
solubility in organic over solubility on aqueous
34
drug incompatibilities arise when __
a drug is mixed with other drugs/products and the result is unsuitable products
35
drug incompatibilities can result in the alteration of physical and chemical __ and the ___ of the active drug
structures; therapeutic effect
36
what are 2 potential concerns if a drug incompatibility causes a change in the chemical/physical structure of the drug?
reduced solubility and/or stability
37
during which steps of the drug making process can incompatibilities occur?
preparation, storage, Administration
38
what are the types of interactions that can happen in drug incompatibilities? (3)
1. pharmacological / pharmacodynamics
2. pharmacokinetic
3. physiochemical
39
physiochemical interactions could involve an interactions with one/more of what 4 factors?
1. other drugs
2. solvents
3. inactive materials (excipients)
4. devices and packaging
40
what is poly pharmacy?
the concurrent use of multiple medications (all to treat one disease)
41
what are the 3 types of drug incompatibilities?
1. physical (pharmaceutical)
2. chemical
3. therapeutic
42
what types of products are made by physical drug incompatibilities?
non-uniform, unacceptable, or unpalatable products
43
what is a dosing issue relative to physical incompatibilities?
the non-uniformity makes it difficult to accurately measure
44
what type of drug incompatibility can result in insolubility, immiscibility, precipitation, liquefaction, adsorption, and complexation of materials?
physical (pharmaceutical)
45
physical drug incompatibilities are preventable using __
pharmaceutical skills
46
chemical drug incompatibilities are due to chemical interactions involving the __
active ingredient
47
If an active ingredient is involved in one of the following reactions: hydrolysis, polymerization, effervescence, oxidation, decomposition, precipitation, what sort of drug incompatibility can arise?
chemical
48
a drug incompatibility that occurs immediately after compounding is called __
immediate
49
a drug incompatibility that occurs later on after compounding is called __
delayed
50
a therapeutic drug incompatibility occurs when
the prescribers intended purpose does not math the therapeutic outcome
51
what are the 2 classes of drug incompatibility prevention?
chemical and physical
52
what are the six methods of prevention against physical incompatibilities?
1. sequence of mxing
2. change solvents
3. change AI type/form
4. change volume
5. emulsification and addition of suspension agents
6. addition, replacement, or removal of unnecessary ingredients
53
low solubility can result in crystallization. The mechanism of drug crystallization is often involves what factor?
pH
54
some IV drugs are unable to be safely mixed due to __
drug crystallization
55
pH of commercially available infusion fluids can vary between __ to ___ pH units. What is the issue with this?
1-2; pH is measured on a log scale, so 1-2 units is actually a big difference, so the drug. may be compatible with 1 batch, but not another
56
what is a common solubility issue associated with pH
crystallization
57
how can the mixing of drugs be done more safely with respect to concerns of pH affecting solubility?
using equations that relate pka to solubility to predict the solubility
58
what are the 7 causes of drug incompatibilities?
1. pH change
2. alteration of solvent characteristics
3. cation--anion interactions
4. effect of salts
5. chelation
6. ion-pair formation
7. adsorption
59
a change in pH often leads to what physical/ chemical change of the drug?
precipitation
60
provide an example of in vitro (in drug) effects of pH change
change in solubility/stability of the active ingredients or excipients
61
solubility of Ca and phosphate in TNP is __ dependent
pH
62
is a low or high pH more suitable for solubility?
low (acidic)
63
what are some (3) in vivo (in patient) effects of pH change?
can neutralize H ions in the stomach, increasing the pH; change rate of gastric emptying; change pH of urine
64
in vivo pH can be altered with ingestion of __, __ and __
antacids, food, weak electrolytes
65
what is the effect of antacids containing Ca on gastric emptying?
slows
66
what is the effect of antacids containing Mg on gastric emptying?
speeds up
67
explain the incompatibility cause of : alteration of solvent characteristics
the solvent can be altered by become diluted (if involved in co-solution with water) and can also be altered by becoming supersaturated if the drug (solute) concentration is too high
68
cation--anion interactions result in the formation of _ through the methods of __, __, or __
insoluble complexes; complexation, precipitation, phase separation
69
explaiin how salting out decreases solubility
highly hydrated non-organic ions deprive organic ions/molecules from getting enough water to dissolve
70
the release of CO2 from carbonated beverages when NaCl is added is an example of the effects of ___ on solubility
salts
71
what is chelation?
complex between a metal atom/ion and an organ anion
72
in chelation, what is the e- acceptor and donor?
acceptor is the metal and donor is the organic
73
chelation results changes in __ and __
solubility and absorption
74
T/F chelation can result in either increased or decrease absorption
true
75
deferiprone is used for treatment of __ by forming a chelate with
iron toxicity; iron
76
EDTA is used for treatment of __ and __ poisoning
lead; mercury
77
tetracycline forms chelates with which metal ions?
Ca, Fe, Mg, Al
78
how does tetracycline use its ability to chelate with Mg ?
uses to target the ribosomes of the bacteria which are rich in Mg
79
what is an adverse effect of tetracycline forming a chelate with ca?
discolouration of teeth
80
explain ion-pair formation
production of neutral species when opposing charges on atoms interact through electrostatics
81
ion-pair formation results in the charges being __
"buried"
82
the products of ion-pair formation are ___ enough to dissolve in non-aqueous solvents
lipophilic
83
provide an example of ion-pair formation
absorption of highly charged drugs
84
what is adsorption?
sticking of dissolved drugs onto surface of adsorbents
85
medical adsorbents are used for __
removing toxic substances form the gut
86
what elements of a drug can act as adsorbents?
the excipients and the packaging
87
proteins/peptides are adsorbed on what type of surfaces?
glass
88
define stability
the extent to which a product retains its same properties throughout its storage and use as it had when it was first mad e
89
what are the 5 types of stability?
1. chemical
2. physical
3. microbial
4. therapeutic
5. topological
90
describe what is meant by "chemical stability"
the active ingredient of the drug maintains its chemical integrity and labeled potency within specified limits
91
describe what is meant by "physical stability"
the original physical properties are maintained (appearance, palatability, uniformity, dissolution, and suspend ability)
92
describe what is meant by "microbial stability"
preservatives maintain effectiveness and microbial growth is resisted
93
describe what is meant by "therapeutic stability"
the therapeutic effect is unchanged
94
describe what is meant by "topological stability"
no significant increase in toxicity
95
what is the temp range for "freezer"?
-25 to -10
96
what is the temp range for "cold"
less than 8
97
what is the temp range for "controlled cold temp?"
2 to 8
98
what is the temp range for "cool"
8 to 15
99
what is the temp range for "room temperature"?
basic temperature of the workspace
100
what is the temp range for " controlled room temp"
20-25
101
what is the temp range for "warm"
30-40
102
what is the temp range for "excessive heat"?
greater than 40
103
a drug that must be stored is a "dry place" must not be stored in a spot with greater than ___ % relative humidity
40
104
what are 2 consequences of drug degradation?
potency loss and change in physical appearance
105
what 5 FG are prone to degradation?
amides, amides, lactones, esters, lactams
106
what are the 5 ways in which drugs can degrade?
1. hydrolysis
2. oxidation
3. isomerization
4. photo-chemical
5. polymerization
107
what 5 FG are susceptible to hydrolysis?
ester, amide, imide, lactam, carbamate
108
Hydrolysis can be catalyzed by 2 different atoms, leading to 2 different kinds of catalysis; what are they?
```
H = acid catalyzed
OH = basic catalyses
```
109
give an example of hydrolysis that happens in penicillin
breaking of the beta lactic ring
110
what are 2 ways you can prevent degradation by hydrolysis?
1. make the drug @ the pH of most stability
| 2. alter the dielectric constant of the solo by adding non-aq solvents
111
oxidation is caused by the addition/removal of a ___
electronegative atom
112
oxidation is catalyses by which atoms?
oxygen and heavy metals
113
oxidation can be automatic, with one step (____), or can happen in a chain rxn of ___, ___, ___
autooxidation; initiation,propogation, termination
114
give 4 examples of compounds suseptible to degradation by oxidation
steroids & sterols, polyunsaturated fats and phenothiazines
115
what are 4 ways we can prevent degradation by oxidation?
1. replace oxygen with CO2 or N2 in drug containers
2. avoid heavy metals
3. store at reduced temp
4. add in antioxidants when making the drug
116
describe the effect of degradation by isomerization
conversion to different optical/geometric isomers, which lowers the therapeutic effect
117
what is the effect of isomerization on epinephrine?
racemisation in acidic soln
118
what is the effect of isomerization on tetracycline?
epimerization in acidic solo
119
cephalosporins undergo isomerization that is catalyses by __
base
120
vitamin A undergoes what type of isomerization?
cis-trans
121
describe photosensitivity in drug degradation
sunlight penetrates the skin and degrades the drug circulating in the surface capillaries
122
phenothiazines, hydrocortisone, prednisolone, riboflavin, ascorbic and folic acid are sensitive to what type of drug degradation?
photochemical
123
what are 2 ways we can prevent degradation by the photochemical route?
1. using amber vials that block wavelengths bellow 470nm
| 2. coating tablets with a polymer film that contains ultraviolet absorbers
124
describe the process of degradation by polymerization
2/more identical drug molecules combine to make a complex compound
125
amino-penicillins are sensitive to what type of degradation?
polymerization
126
how can degradation by polymerization be prevented?
monitor polarity of the aq solvent
127
what are 5 factors that affect the drug stability of liquids?
1. pH
2. temp/light
3. ionic and solvent effect
4. oxidizing agents
5. surfactants
128
what are 3 factors that affect drug stability of solids?
1. temp/light
2. moisture
3. oxidizing compounds
129
what is the relationship of zero order rate of degradation to concentration?
no relationship (independent of each other)
130
what is the relationship of first order rate of degradation to concentration>
rate is dependent on 1 concentration
131
what is the relationship of second order rate of degradation to concentration?
rate is dependant on 2 concentrations
132
drug suspension with poorly water soluble drugs are __ order of degradation
zero
133
zero order drug degradation have __ rate of depletion of drug
constant
134
the half-life of second order degradation is dependent on the ___ of reactants
initial concentrations
135
what can be used to calculate shelf-life?
degradation kinetics (accelerated stability testing0
136
what theory / set of equations are used to calculate stability and shelf-life?
Arrhenius
