E#2 Buffer and Isotonicity Flashcards
(187 cards)
1
Q
what is a buffer solution?
A
can maintain a desired pH at a relatively constant level when a small quantity of an acid or base is added
2
Q
what are the two types of buffer solutions?
A
a weak acid with its conjugate base
a weak base with its conjugate acid
3
Q
what is a conjugate base?
A
a salt of the acid
4
Q
what is a conjugate acid?
A
a salt of the base
5
Q
why cant strong acids and bases be used as a buffer?
A
because they completely dissociate
6
Q
eg. of a weak acid and conjugate base buffer
A
acetic acid and sodium acetate
7
Q
eg. of a weak base and conjugate acid buffer
A
ammonia and ammonia chloride
8
Q
what do the concentrations of a buffer have to be and what is this because of?
A
equal concentrations of acid/base and conjugate base/acid
b/c of buffer capacity
9
Q
what is the formula for a weak acid and conjugate base buffer?
A
HA + OH- <—> A- + H2O
10
Q
what is the formula for a weak base and conjugate acid buffer?
A
A- + H3O+ <—> HA + OH-
11
Q
Henderson-Hasselbalch Equation for an acidic / alkaline buffer solutions?
A
acidic
pH = pka + log [salt/acid]
alkaline
pH = pka + log [base/salt]
12
Q
when does pkw= 14
A
25°C
13
Q
what is the pkw equation?
A
pkw = pka + pkb
pH = pOH + pH
14
Q
what is the common ion effect?
A
When more of a common ion is added, more of the ion increases, so the precipitate increases
15
Q
What is momentarily distrubed when more of a common ion is added supplied by the salt?
A
the Ka
16
Q
when more sodium acetate is added to acetic acid, what happens to the ionization?
A
the ionization fo HAc is repressed becasue more [Ac-] is added (common ion effect)
HAc + H2O <–> H3O+ + Ac-
17
Q
what is the Ka and Kb equation?
A
K = [aqueous product][aqueous product] / [aqueous reactants][aqueous reactants]
18
Q
What is the Henderson-Hasselbalch equation?
A
pH = pKa + log [A-]/[HA]
19
Q
what is the dissociation constant/ionization constant
A
ka or kb
20
Q
what is the pkw
what is the equation
A
pkw = 14 at 25°C
pkw = pka +pkb
21
Q
how is acidity measured
A
concentration of H+ ions
22
Q
how much is one unit change on the pH scale
A
tenfold change in H+ concentration
23
Q
what is the ion concentration of a neutral buffer
A
H+ = OH-
24
Q
what is the pH scale equation wise
A
logarithmic
25
what happens when u add acid or base to a buffer
increase base
increase pH
decrease buffer capacity
increase acid
decrease pH
decrease buffer capacity
26
Is buffer capacity a fixed value?
no
27
what is buffer capacity dependent on?
the amount of base added
dependent of the [base]/[acid]
dependent on the magnitude of the individual concentrations of the buffer components
28
what is the buffer capacity higher for when
[HA] > [A⁻]
[A⁻] > [HA]
[HA] > [A⁻]
higher for added base than acid
[A⁻] > [HA]
higher for added acid than base
29
what is Bmax
the greatest buffer capacity
30
where does the greatest buffer capacity occur
[base]/[acid] = 1
pH = pka
31
what do buffer capacities not exceed?
why?
0.2
interionic effects
32
what is the pH of blood?
7.4
33
how is the pH of blood maintained
primary buffers in the plasma
secondary buffers in erythrocytes
plasma proteins
34
how do primary buffers in the plasma maintain blood pH
carbonic acid / bicarbonate
acid / alkali sodium salts of phosphoric acid
35
how do secondary buffers in erythrocytes maintain blood pH
hemoglobin / oxyhemoglobin
acid / alkali potassium salts of phosphoric acid
36
how do plasma proteins maintain blood pH
combine acids in blood with bases so act as buffers
37
how does buffering influence the solubility of base at a low pH
base is ionic form
usually very soluble in aqueous media
38
how does buffering influence the solubility of base as the pH is raised higher
more undissociated base is formed when the base exceeds the limit water solubility of this form
free base precipitates from solution
39
how should a buffer be prepared for stabilization against precipitation of a base solution
base solution buffered at a sufficiently low pH
40
what is the van't hoff factor
i
41
Van't Hoff Factor equation
42
a system in which molecules of a solute are dissolved in a solvent
solution
43
what is solubility
concentration of solute in a saturated solution at a certain temperature
intrinsic property of a solute
44
unsaturated solution
aka subsaturated
concentration of dissolved solute is below complete saturation amount at a definite temperature
45
saturated solution
solute dissolves until it is unable to dissolve any more
undissolved substances at bottom
46
supersaturated solution
contains more dissolved solute than normal at a definite temperature
47
what is present is greater quantity in a solution
solvent
48
what are the three types of solvents
polar
nonpolar
semipolar
49
what can be gases, liquids, or solids in a solution
solute
50
types of solutes
non-electrolytes
electrolytes
-strong
-weak
51
non-electrolytes
do not form ions when dissolved in water
do not conduct electricity
52
electrolytes
form ion in solution
conduct electric current
53
strong electrolyte
completely ionize in water
54
weak electrolyte
partially ionize in water
55
eg. of non-electrolyte solutes
estradiol
glycerin
urea
sucrose
56
eg. of electrolyte solutes
*strong*
NaCl
HCl
*weak*
aspirin
atropine
57
what was the solubility we did in lab
200 mg/ml
freely soluble
1-10 parts solvent for 1 solute
58
very soluble
*parts solvent for one part solute*
<1 part solvent
*solubility (mg/ml)*
>1000
59
freely soluble
*parts solvent for one part solute*
1-10
*solubility (mg/ml)*
100-1000
60
soluble
*parts solvent for one part solute*
10-30
*solubility (mg/ml)*
33-100
61
sparingly soluble
*parts solvent for one part solute*
30-100
*solubility (mg/ml)*
10-33
62
slightly soluble
*parts solvent for one part solute*
100-1,000
*solubility (mg/ml)*
1-10
63
very slightly soluble
*parts solvent for one part solute*
1,000-10,000
*solubility (mg/ml)*
0.1-1
64
practically insoluble
*parts solvent for one part solute*
>10,000
*solubility (mg/ml)*
<0.1
65
what factors affect solubility
1. the physical and chemical properties of the solute
2. temperature
3. pressure
4. pH of the solution
5. polarity
66
true or false
a polar solvent means that it will dissolve because it is an electrolyte
false
it may or may not dissolve
does not have to be electrolyte
67
what do polar solutes dissolve
ionic solutes
polar substances
68
what does the solubility of a drug in polar solvents depend on
1. the polarity of the solute and solvent
2. ability of solute to form hydrogen bonds
3. ratio of polar and nonpolar groups of the molecule
69
why solute's ability to form H bonds affects solubility in a polar solvent
how is solubility effected
*polar substances dissolves O, N containing compounds* (makes H bonds with water)
70
example of O and N containing compounds
phenols
alcohols
aldehydes
ketones
amines
71
how does ratio of polar to nonpolar groups of molecules affect solubility in a polar solvent
additional polar groups increases solubility
increases length of nonpolar chain decreases (water) solubility
branching c chain
72
eg. of increased length of nonpolar chain decreasing (water) solubility
*slightly soluble*
straight chain monohydroxy alcohols
aldehydes
acids with more than 4 carbons
*cannot enter into H bonded structure of water*
73
Are hydroxyl groups polar or nonpolar?
polar
74
does the branching carbons chain make a molecule more or less polar and more or less soluble in water (polar)
branching C chain increases polar solubility by making more polar
75
are organic molecules polar or nonpolar
nonpolar
76
are molecules without OH polar or nonpolar
nonpolar
77
what can nonpolar solvents dissolve
molecules that are not ionic and nonpolar
dissolve nonpolar solutes with similar attractive forces through induced dipole interactions (London Forces)
78
list of nonpolar solvents
hydrocarbons
chloroform
toluene
hexane
dichloromethane
79
list of polar solvents
water
methanol
ethanol
acetonitrile
isopropanol
80
why can nonpolar solvents not dissolve ionic and polar solutes
cannot reduce attraction between ions because of the solvents low dielectric constants
cannot break covalent bonds to make or ionize the weak electrolytes because they are aprotic
cannot form hydrogen bridges with nonelectrolytes
81
what does aprotic mean
no hydrogen
82
eg. of a nonpolar solvent that can dissolve a nonpolar solute with similar attractive forces
CCl4 - solvent
oil and fats - solute
83
what are semipolar solvents
induce certain degree of polarity in nonpolar solvents
84
what do semipolar solvents at as
intermediate solvents that generate miscibility between polar and nonpolar liquids
85
eg. of semipolar solvents
acetone increases solubility of ether in water
alcohol actions on water-caster oil mixtures
86
what does complete miscibility mean
liquid mixes in all proportions
87
what does partial miscibility mean
two layers form when liquids are mixed
each layer contains some of other liquid in dissolved state
88
eg. of a complete miscibility in a mixture
water-alcohol
glycerin-alcohol
alcohol-acetone
benzene-CCl4
89
eg. of a partial miscibility in a mixture
water-ether
water-phenol
90
solubility equation for a weak acid
St = [HAsolution] +[A-solution]
St = [So] +[A-solution]
91
solubility equation for a weak acid
St = [Bsol] + [BH+]
St = [So](1+[kb]/[OH-])
92
equation: solubility related to pH
93
what does intrinsic (saturated) solubility equal for a weak acid
So = [HAsolution]
94
what is the pka and ka at a low pH
pH << pka
[H+] >> ka
95
what pH is the most unionized form for a weak acid?
low pH
96
what pH is the most unionized form for a weak base?
high pH
97
relationship of St and So for a weak acid with a low pH
St = [So]
98
relationship of St and So for a weak base with a low pH
will be a big number so must calculate
99
relationship of St and So for a weak acid with a medium pH
St = [So] * 2
total solubility = twice intrinsic solubility
100
relationship of St and So for a weak base with a medium pH
St = [So] * 2
total solubility = twice intrinsic solubility
101
relationship of St and So for a weak acid with a high pH
will be a big number so must calculate
102
relationship of St and So for a weak base with a high pH
St = [So]
103
what is the pka and ka at a medium pH
pH = pka
[H+] = ka
104
what is the pka and ka at a high pH
pH >> pka
[H+] << ka
105
when are weak acids protonated and non ionized
pH below their pka
106
when are weak acids de-protonated and ionized
pH above their pka
107
what is solubility of a weak acid defined by when pH is above their pka
total solubility defined by ...
intrinsic solubility
increased concentration of more soluble ionized form
108
what is solubility of a weak acid defined by when pH is below their pka
solubility defined by intrinsic solubility
109
when are bases de-protonated and non-ionized
pH above their pka
110
when are bases protonated and ionized
pH below their pka
111
what is solubility of a weak base defined by when pH is above their pka
solubility defined by intrinsic solubility
112
what is solubility of a weak base defined by when pH is below their pka
total solubility defined by ...
intrinsic solubility
increased concentration of more soluble ionized form
113
what must you check for cosolvents to form optimum cosolvent systems
physical parameters of the cosolvent
114
eg. of physical parameters of the cosolvent
dielectric constant
polarity
115
what are cosolvents
blending of multiple solvents to enhance the drug solubility
116
what drug example need to use a cosolvent
ethanol
117
why are cosolvents used
a drug is not water soluble enough
a drug is too soluble in an undesired solvent
118
what can also be a problem with solubility in a solution with cosolvents
drug dissolves in non aqueous solvent
precipitates out of solution when mixed into aqueous system
119
1. what are most solvent blends limited to
2. why
1. mixtures containing...
water
ethanol
glycerin
propylene glycol
polyethylene glycol 400
sorbitol solution
2. because many solvents may be toxic when ingested
*a lil more for external application*
120
what is used to increase the concentration of the unionized form of the drug
cosolvents or non-ionic solvents
121
eg. of cosolvents or non-ionic solvents
alcohol
propylene glycol
glycerol
122
how can the total amount of drug dissolved be increased
eg.
Increasing So
valium for injection: 40% PPG + 10% EtOH
compounding cough syrups
-codeine more soluble in EtOH than syrup base
-dissovled in EtOH first
123
partioning
movement of molecules from one phase to another
124
what will happen to the solute if two immiscible phases are placed next to each other
solute will distribute until equilibrium reached
125
what will happen when a substance is added in excess to two immiscible solvents
distributes until both liquid phases become saturated
126
what is the distribution of a solute between immiscible liquids known as
Nernst's distribution law
distribution law
partition law
127
what does the Nernst distribution law state
when added substance is insufficient to saturate immiscible liquids
solute distributes to reach equilibrium of ratio of concentration (at a constant temperature)
128
partition coefficient
ratio of unionized drug in organic phase and aqueous phase at equilibrium
129
partition coefficeint (p) equation
p = [drug in organic phase] / [drug in aqueous phase]
130
a measure of differential solubility of the compound between two solvents
p
partition coefficient
131
what controls the partition coefficient
pka
132
what molecules are lipid soluble
only unionized
133
what is the lipophilicity of an organic compound usually described in terms of
partition coefficient
log P
134
what is used since it is virtually impossible to determine log P in a realistic biological medium
the octanol:water system
*a model of the lipid phase*
135
log P calculation... what stands for what
136
when is the drug more likely to dissolve well in body and why
when the partition coefficient is 0
log (1) = 0
equal solubility in organic and aqueous
equally hydrophilic and hydrophobic
137
is Log P = 3 more hydrophilic or hydrophobic
log P = 3
P = 1000
1000 times more hydrophobic than hydrophilic
138
log P = 0
equal distribution of the drug in both phases
139
log P > 0
the drug has higher affinity for lipid phase
140
log P < 0
the drug has higher affinity for aqueous phase
141
142
why can the drug permeability be more complicated
most drugs ionize in an aqueous solution
143
what are drugs that ionize in an aqueous solution characterized by
distribution constant (D)
144
what is the distribution constant dependent on
pH
145
what is the distribution constant
ratio of sum of concentration of all forms of the compound in each of the two phases
146
what helps to determine apparent partition coefficient at any pH
knowledge of the pka
147
what is the drug disribution coefficient equation and what stands for what
148
149
150
what is the rate limiting step for these drugs (oral consumption)
especially for...
-basic drugs
-low solubility drugs / acidic drugs
-polar drugs & low permeability
-congestive heart failure
gastric emptying rate
dissolution
GI wall permeation rate
mesenteric / splanchnic perfusion rate
-disease rate
151
which rate limiting step (oral consumption) is for what type of drugs
-gastric emptying rate
-dissolution
-GI wall permeation rate
-mesenteric / splanchnic perfusion rate
-disease rate
especially for...
-basic drugs
-low solubility drugs / acidic drugs
-polar drugs & low permeability
-congestive heart failure
152
why is evaluation of drug performance needed
pharmacological effect of drug and drug product
critical to clinical safety and efficacy
required for drug development
153
what are the two types of performance evaluations
in-vivo
in-vitro
154
what does in-vivo lead to / when is in-vivo needed
release of drug leading to bioavailability
-bioavailability study (BA study)
-bioequivalence study (BE study)
155
what does in-vitro lead to / when is in-vitro needed
drug release from the dosage forms
-drug product development
-drug product quality assessment
156
in-vitro
evaluation of the performance of the dosage forms in a non-clinical setting
157
what are the three testings you can do for in-vitro
disintegration testing
dissolution testing
drug release rate
158
what does disintegration testing do
the ability of a sample to break into smaller particles
159
what does dissolution testing do
the amount of drug dissolved in dissolution media over time
160
what does drug release rate test for
amount of drug released from the dosage form / delivery system overtime
161
what are each of the in-vitro tests used for?
disintegration testing
-tablets
-capsules
dissolution testing
-suspensions
-powders
-capsules
-tablets (IR or ER)
drug release rate
-creams
-gels
-transdermal patches
-inserts
162
what characteristics of drug products / formulations are tested for in-vitro testing
drug property changes
formulation changes
manufacturing process changes
163
drug property changes examples
particle size
polymorphs and solvates
164
formulation changes examples
type of excipients
amount of each excipient
165
manufacturing process changes examples
compression forces
manufacturing sites
166
what is the purpose of dissolution testing
formulation development and selection
drug quality evaluation
-batch to batch reproducibility
-drug product stability
in-vitro and in-vivo correlation (IVIVC)
167
what is dissolution rate related to
surface area of particles (drug and formulation)
thickness of the stagnant layer (agitation)
solubility of the drug (in dissolution media)
168
Noyes-Whitney equation
dM = change in mass of solute
dt = change in time
169
170
171
what is some dissolutions media used
purified water
0.1 N HCl
buffer solutions (pH 2-7)
-phosphate buffers
surfacants
-to improve solubiltiy
bio-relevant media
172
types of bio-relevant media
stimulated gastric fluid (SGF)
simulated intestinal fluid (SIF)
-fasted state (FASSIF)
-fed state (FESSIF)
173
how much dissolution medium should be used to for a sink condition
the volume should be greater than 3x needed for a saturated solution
174
true or false
bioavailability studies are more sensitive than discriminating dissolution tests
false
discriminating dissolution tests are more sensitive than bioavailability studies
-patient variation
175
what do discriminating dissolution tests detect changes in
polymorph of crystalline structures
size
formulation
-grade and quality
manufacturing process
-granule size
-hardness of tablets
stability
176
FaSSIF
177
FeSSIF
178
FaSSGF
179
180
181
182
183
184
185
186
187
