E#2 Buffer and Isotonicity Flashcards

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

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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

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3
Q

what is a conjugate base?

A

a salt of the acid

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4
Q

what is a conjugate acid?

A

a salt of the base

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5
Q

why cant strong acids and bases be used as a buffer?

A

because they completely dissociate

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6
Q

eg. of a weak acid and conjugate base buffer

A

acetic acid and sodium acetate

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7
Q

eg. of a weak base and conjugate acid buffer

A

ammonia and ammonia chloride

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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

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9
Q

what is the formula for a weak acid and conjugate base buffer?

A

HA + OH- <—> A- + H2O

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10
Q

what is the formula for a weak base and conjugate acid buffer?

A

A- + H3O+ <—> HA + OH-

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11
Q

Henderson-Hasselbalch Equation for an acidic / alkaline buffer solutions?

A

acidic
pH = pka + log [salt/acid]

alkaline
pH = pka + log [base/salt]

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12
Q

when does pkw= 14

A

25°C

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13
Q

what is the pkw equation?

A

pkw = pka + pkb
pH = pOH + pH

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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

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15
Q

What is momentarily distrubed when more of a common ion is added supplied by the salt?

A

the Ka

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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-

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17
Q

what is the Ka and Kb equation?

A

K = [aqueous product][aqueous product] / [aqueous reactants][aqueous reactants]

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18
Q

What is the Henderson-Hasselbalch equation?

A

pH = pKa + log [A-]/[HA]

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19
Q

what is the dissociation constant/ionization constant

A

ka or kb

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20
Q

what is the pkw
what is the equation

A

pkw = 14 at 25°C
pkw = pka +pkb

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21
Q

how is acidity measured

A

concentration of H+ ions

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22
Q

how much is one unit change on the pH scale

A

tenfold change in H+ concentration

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23
Q

what is the ion concentration of a neutral buffer

A

H+ = OH-

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24
Q

what is the pH scale equation wise

A

logarithmic

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25
Q

what happens when u add acid or base to a buffer

A

increase base
increase pH
decrease buffer capacity

increase acid
decrease pH
decrease buffer capacity

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26
Q

Is buffer capacity a fixed value?

A

no

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27
Q

what is buffer capacity dependent on?

A

the amount of base added

dependent of the [base]/[acid]

dependent on the magnitude of the individual concentrations of the buffer components

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28
Q

what is the buffer capacity higher for when

[HA] > [A⁻]
[A⁻] > [HA]

A

[HA] > [A⁻]
higher for added base than acid

[A⁻] > [HA]
higher for added acid than base

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29
Q

what is Bmax

A

the greatest buffer capacity

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30
Q

where does the greatest buffer capacity occur

A

[base]/[acid] = 1

pH = pka

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31
Q

what do buffer capacities not exceed?
why?

A

0.2
interionic effects

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32
Q

what is the pH of blood?

A

7.4

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33
Q

how is the pH of blood maintained

A

primary buffers in the plasma
secondary buffers in erythrocytes
plasma proteins

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34
Q

how do primary buffers in the plasma maintain blood pH

A

carbonic acid / bicarbonate

acid / alkali sodium salts of phosphoric acid

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35
Q

how do secondary buffers in erythrocytes maintain blood pH

A

hemoglobin / oxyhemoglobin

acid / alkali potassium salts of phosphoric acid

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36
Q

how do plasma proteins maintain blood pH

A

combine acids in blood with bases so act as buffers

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37
Q

how does buffering influence the solubility of base at a low pH

A

base is ionic form

usually very soluble in aqueous media

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38
Q

how does buffering influence the solubility of base as the pH is raised higher

A

more undissociated base is formed when the base exceeds the limit water solubility of this form

free base precipitates from solution

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39
Q

how should a buffer be prepared for stabilization against precipitation of a base solution

A

base solution buffered at a sufficiently low pH

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40
Q

what is the van’t hoff factor

A

i

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41
Q

Van’t Hoff Factor equation

A
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42
Q

a system in which molecules of a solute are dissolved in a solvent

A

solution

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43
Q

what is solubility

A

concentration of solute in a saturated solution at a certain temperature

intrinsic property of a solute

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44
Q

unsaturated solution

A

aka subsaturated

concentration of dissolved solute is below complete saturation amount at a definite temperature

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45
Q

saturated solution

A

solute dissolves until it is unable to dissolve any more

undissolved substances at bottom

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46
Q

supersaturated solution

A

contains more dissolved solute than normal at a definite temperature

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47
Q

what is present is greater quantity in a solution

A

solvent

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48
Q

what are the three types of solvents

A

polar
nonpolar
semipolar

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49
Q

what can be gases, liquids, or solids in a solution

A

solute

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50
Q

types of solutes

A

non-electrolytes

electrolytes
-strong
-weak

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51
Q

non-electrolytes

A

do not form ions when dissolved in water

do not conduct electricity

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52
Q

electrolytes

A

form ion in solution

conduct electric current

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53
Q

strong electrolyte

A

completely ionize in water

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54
Q

weak electrolyte

A

partially ionize in water

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55
Q

eg. of non-electrolyte solutes

A

estradiol
glycerin
urea
sucrose

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56
Q

eg. of electrolyte solutes

A

strong
NaCl
HCl

weak
aspirin
atropine

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57
Q

what was the solubility we did in lab

A

200 mg/ml

freely soluble

1-10 parts solvent for 1 solute

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58
Q

very soluble

A

parts solvent for one part solute
<1 part solvent

solubility (mg/ml)
>1000

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59
Q

freely soluble

A

parts solvent for one part solute
1-10

solubility (mg/ml)
100-1000

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60
Q

soluble

A

parts solvent for one part solute
10-30

solubility (mg/ml)
33-100

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61
Q

sparingly soluble

A

parts solvent for one part solute
30-100

solubility (mg/ml)
10-33

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62
Q

slightly soluble

A

parts solvent for one part solute
100-1,000

solubility (mg/ml)
1-10

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63
Q

very slightly soluble

A

parts solvent for one part solute
1,000-10,000

solubility (mg/ml)
0.1-1

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64
Q

practically insoluble

A

parts solvent for one part solute
>10,000

solubility (mg/ml)
<0.1

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65
Q

what factors affect solubility

A
  1. the physical and chemical properties of the solute
  2. temperature
  3. pressure
  4. pH of the solution
  5. polarity
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66
Q

true or false

a polar solvent means that it will dissolve because it is an electrolyte

A

false
it may or may not dissolve
does not have to be electrolyte

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67
Q

what do polar solutes dissolve

A

ionic solutes
polar substances

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68
Q

what does the solubility of a drug in polar solvents depend on

A
  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
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69
Q

why solute’s ability to form H bonds affects solubility in a polar solvent

how is solubility effected

A

polar substances dissolves O, N containing compounds (makes H bonds with water)

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70
Q

example of O and N containing compounds

A

phenols
alcohols
aldehydes
ketones
amines

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71
Q

how does ratio of polar to nonpolar groups of molecules affect solubility in a polar solvent

A

additional polar groups increases solubility

increases length of nonpolar chain decreases (water) solubility

branching c chain

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72
Q

eg. of increased length of nonpolar chain decreasing (water) solubility

A

slightly soluble
straight chain monohydroxy alcohols
aldehydes
acids with more than 4 carbons

cannot enter into H bonded structure of water

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73
Q

Are hydroxyl groups polar or nonpolar?

A

polar

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74
Q

does the branching carbons chain make a molecule more or less polar and more or less soluble in water (polar)

A

branching C chain increases polar solubility by making more polar

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75
Q

are organic molecules polar or nonpolar

A

nonpolar

76
Q

are molecules without OH polar or nonpolar

A

nonpolar

77
Q

what can nonpolar solvents dissolve

A

molecules that are not ionic and nonpolar

dissolve nonpolar solutes with similar attractive forces through induced dipole interactions (London Forces)

78
Q

list of nonpolar solvents

A

hydrocarbons
chloroform
toluene
hexane
dichloromethane

79
Q

list of polar solvents

A

water
methanol
ethanol
acetonitrile
isopropanol

80
Q

why can nonpolar solvents not dissolve ionic and polar solutes

A

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
Q

what does aprotic mean

A

no hydrogen

82
Q

eg. of a nonpolar solvent that can dissolve a nonpolar solute with similar attractive forces

A

CCl4 - solvent
oil and fats - solute

83
Q

what are semipolar solvents

A

induce certain degree of polarity in nonpolar solvents

84
Q

what do semipolar solvents at as

A

intermediate solvents that generate miscibility between polar and nonpolar liquids

85
Q

eg. of semipolar solvents

A

acetone increases solubility of ether in water

alcohol actions on water-caster oil mixtures

86
Q

what does complete miscibility mean

A

liquid mixes in all proportions

87
Q

what does partial miscibility mean

A

two layers form when liquids are mixed

each layer contains some of other liquid in dissolved state

88
Q

eg. of a complete miscibility in a mixture

A

water-alcohol
glycerin-alcohol
alcohol-acetone
benzene-CCl4

89
Q

eg. of a partial miscibility in a mixture

A

water-ether
water-phenol

90
Q

solubility equation for a weak acid

A

St = [HAsolution] +[A-solution]
St = [So] +[A-solution]

91
Q

solubility equation for a weak acid

A

St = [Bsol] + [BH+]
St = So

92
Q

equation: solubility related to pH

A
93
Q

what does intrinsic (saturated) solubility equal for a weak acid

A

So = [HAsolution]

94
Q

what is the pka and ka at a low pH

A

pH &laquo_space;pka
[H+]&raquo_space; ka

95
Q

what pH is the most unionized form for a weak acid?

A

low pH

96
Q

what pH is the most unionized form for a weak base?

A

high pH

97
Q

relationship of St and So for a weak acid with a low pH

A

St = [So]

98
Q

relationship of St and So for a weak base with a low pH

A

will be a big number so must calculate

99
Q

relationship of St and So for a weak acid with a medium pH

A

St = [So] * 2

total solubility = twice intrinsic solubility

100
Q

relationship of St and So for a weak base with a medium pH

A

St = [So] * 2

total solubility = twice intrinsic solubility

101
Q

relationship of St and So for a weak acid with a high pH

A

will be a big number so must calculate

102
Q

relationship of St and So for a weak base with a high pH

A

St = [So]

103
Q

what is the pka and ka at a medium pH

A

pH = pka
[H+] = ka

104
Q

what is the pka and ka at a high pH

A

pH&raquo_space; pka
[H+] &laquo_space;ka

105
Q

when are weak acids protonated and non ionized

A

pH below their pka

106
Q

when are weak acids de-protonated and ionized

A

pH above their pka

107
Q

what is solubility of a weak acid defined by when pH is above their pka

A

total solubility defined by …

intrinsic solubility
increased concentration of more soluble ionized form

108
Q

what is solubility of a weak acid defined by when pH is below their pka

A

solubility defined by intrinsic solubility

109
Q

when are bases de-protonated and non-ionized

A

pH above their pka

110
Q

when are bases protonated and ionized

A

pH below their pka

111
Q

what is solubility of a weak base defined by when pH is above their pka

A

solubility defined by intrinsic solubility

112
Q

what is solubility of a weak base defined by when pH is below their pka

A

total solubility defined by …

intrinsic solubility
increased concentration of more soluble ionized form

113
Q

what must you check for cosolvents to form optimum cosolvent systems

A

physical parameters of the cosolvent

114
Q

eg. of physical parameters of the cosolvent

A

dielectric constant
polarity

115
Q

what are cosolvents

A

blending of multiple solvents to enhance the drug solubility

116
Q

what drug example need to use a cosolvent

A

ethanol

117
Q

why are cosolvents used

A

a drug is not water soluble enough
a drug is too soluble in an undesired solvent

118
Q

what can also be a problem with solubility in a solution with cosolvents

A

drug dissolves in non aqueous solvent

precipitates out of solution when mixed into aqueous system

119
Q
  1. what are most solvent blends limited to
  2. why
A
  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
Q

what is used to increase the concentration of the unionized form of the drug

A

cosolvents or non-ionic solvents

121
Q

eg. of cosolvents or non-ionic solvents

A

alcohol
propylene glycol
glycerol

122
Q

how can the total amount of drug dissolved be increased
eg.

A

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
Q

partioning

A

movement of molecules from one phase to another

124
Q

what will happen to the solute if two immiscible phases are placed next to each other

A

solute will distribute until equilibrium reached

125
Q

what will happen when a substance is added in excess to two immiscible solvents

A

distributes until both liquid phases become saturated

126
Q

what is the distribution of a solute between immiscible liquids known as

A

Nernst’s distribution law
distribution law
partition law

127
Q

what does the Nernst distribution law state

A

when added substance is insufficient to saturate immiscible liquids

solute distributes to reach equilibrium of ratio of concentration (at a constant temperature)

128
Q

partition coefficient

A

ratio of unionized drug in organic phase and aqueous phase at equilibrium

129
Q

partition coefficeint (p) equation

A

p = [drug in organic phase] / [drug in aqueous phase]

130
Q

a measure of differential solubility of the compound between two solvents

A

p
partition coefficient

131
Q

what controls the partition coefficient

A

pka

132
Q

what molecules are lipid soluble

A

only unionized

133
Q

what is the lipophilicity of an organic compound usually described in terms of

A

partition coefficient
log P

134
Q

what is used since it is virtually impossible to determine log P in a realistic biological medium

A

the octanol:water system

a model of the lipid phase

135
Q

log P calculation… what stands for what

A
136
Q

when is the drug more likely to dissolve well in body and why

A

when the partition coefficient is 0
log (1) = 0

equal solubility in organic and aqueous
equally hydrophilic and hydrophobic

137
Q

is Log P = 3 more hydrophilic or hydrophobic

A

log P = 3
P = 1000
1000 times more hydrophobic than hydrophilic

138
Q

log P = 0

A

equal distribution of the drug in both phases

139
Q

log P > 0

A

the drug has higher affinity for lipid phase

140
Q

log P < 0

A

the drug has higher affinity for aqueous phase

141
Q
A
142
Q

why can the drug permeability be more complicated

A

most drugs ionize in an aqueous solution

143
Q

what are drugs that ionize in an aqueous solution characterized by

A

distribution constant (D)

144
Q

what is the distribution constant dependent on

A

pH

145
Q

what is the distribution constant

A

ratio of sum of concentration of all forms of the compound in each of the two phases

146
Q

what helps to determine apparent partition coefficient at any pH

A

knowledge of the pka

147
Q

what is the drug disribution coefficient equation and what stands for what

A
148
Q
A
149
Q
A
150
Q

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

A

gastric emptying rate

dissolution

GI wall permeation rate

mesenteric / splanchnic perfusion rate
-disease rate

151
Q

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

A

especially for…
-basic drugs
-low solubility drugs / acidic drugs
-polar drugs & low permeability
-congestive heart failure

152
Q

why is evaluation of drug performance needed

A

pharmacological effect of drug and drug product

critical to clinical safety and efficacy

required for drug development

153
Q

what are the two types of performance evaluations

A

in-vivo
in-vitro

154
Q

what does in-vivo lead to / when is in-vivo needed

A

release of drug leading to bioavailability
-bioavailability study (BA study)
-bioequivalence study (BE study)

155
Q

what does in-vitro lead to / when is in-vitro needed

A

drug release from the dosage forms
-drug product development
-drug product quality assessment

156
Q

in-vitro

A

evaluation of the performance of the dosage forms in a non-clinical setting

157
Q

what are the three testings you can do for in-vitro

A

disintegration testing
dissolution testing
drug release rate

158
Q

what does disintegration testing do

A

the ability of a sample to break into smaller particles

159
Q

what does dissolution testing do

A

the amount of drug dissolved in dissolution media over time

160
Q

what does drug release rate test for

A

amount of drug released from the dosage form / delivery system overtime

161
Q

what are each of the in-vitro tests used for?

A

disintegration testing
-tablets
-capsules

dissolution testing
-suspensions
-powders
-capsules
-tablets (IR or ER)

drug release rate
-creams
-gels
-transdermal patches
-inserts

162
Q

what characteristics of drug products / formulations are tested for in-vitro testing

A

drug property changes
formulation changes
manufacturing process changes

163
Q

drug property changes examples

A

particle size
polymorphs and solvates

164
Q

formulation changes examples

A

type of excipients
amount of each excipient

165
Q

manufacturing process changes examples

A

compression forces
manufacturing sites

166
Q

what is the purpose of dissolution testing

A

formulation development and selection

drug quality evaluation
-batch to batch reproducibility
-drug product stability

in-vitro and in-vivo correlation (IVIVC)

167
Q

what is dissolution rate related to

A

surface area of particles (drug and formulation)

thickness of the stagnant layer (agitation)

solubility of the drug (in dissolution media)

168
Q

Noyes-Whitney equation

A

dM = change in mass of solute
dt = change in time

169
Q
A
170
Q
A
171
Q

what is some dissolutions media used

A

purified water
0.1 N HCl
buffer solutions (pH 2-7)
-phosphate buffers
surfacants
-to improve solubiltiy
bio-relevant media

172
Q

types of bio-relevant media

A

stimulated gastric fluid (SGF)

simulated intestinal fluid (SIF)
-fasted state (FASSIF)
-fed state (FESSIF)

173
Q

how much dissolution medium should be used to for a sink condition

A

the volume should be greater than 3x needed for a saturated solution

174
Q

true or false
bioavailability studies are more sensitive than discriminating dissolution tests

A

false
discriminating dissolution tests are more sensitive than bioavailability studies
-patient variation

175
Q

what do discriminating dissolution tests detect changes in

A

polymorph of crystalline structures
size
formulation
-grade and quality
manufacturing process
-granule size
-hardness of tablets
stability

176
Q

FaSSIF

A
177
Q

FeSSIF

A
178
Q

FaSSGF

A
179
Q
A
180
Q
A
181
Q
A
182
Q
A
183
Q
A
184
Q
A
185
Q
A
186
Q
A
187
Q
A