Lecture 2: Solubility Flashcards

1
Q

Drugs must be in a solution form for

A

-absorption
-distribution
-reaching site of action
-elimination

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2
Q

Solubility issues

A

-bodily fluids mostly aqueous
-most drugs hydrophobic
-many drugs hard to solubilize

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3
Q

Factors reducing solubility

A

= difficulty of dislodging solute molecules from crystal + difficulty of solvating dislodged molecules

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4
Q

Crystal

A

-strength makes it harder for solute molecules to dislodge
-even if mixed well, this gives difficult solubility

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5
Q

Making a solution

A

-solid –> liquid by melting
-liquid –> solution by mixing solvent

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6
Q

crystallinity

A

-solid –> liquid by “melting”
-difficulty of dislodging molecules from crystal
-(∆Hm/2.303RT)((Tm-T)/Tm)
-ideal solubility (log Xideal)

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7
Q

Hydrophobicity

A

-liquid –> solution by “mixing” solvent
-difficulty of solvating molecules
- -log y

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8
Q

Factors controlling solubility

A

log Xobs = -(∆Hm/2.303RT)((Tm-T)/Tm) -log y

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9
Q

Graph of Solubility Equation

A

SLIDE 9
-Log Xobs = horizontal baseline
-Log Xideal= black box above baseline
- -log y = white box on top of black box to 0

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10
Q

Breakdown of solubility contributions

A

Slide 10

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11
Q

“like dissolves like”

A

-would be true if everything was liquid INSTEAD:
-higher melting point of solid = lower solubility

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12
Q

Higher melting point

A

lower solubilty

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13
Q

Dissolution

A

-end goal for drug
-solubility affects rate

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14
Q

Noyes-Whitney Equation

A

(dC/dt) = DA/h (Cs-C)

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15
Q

Tablet to tissue

A

tablet to GI tract to intestinal wall to systemic circulation to target tissue

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16
Q

GI tract

A

-solubility/dissolution
-stability
sends to intestinal wall

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17
Q

Intestinal wall

A

-permeability
-stability
sends to circulation

18
Q

Systemic Circulation

A

-first-pass
-metabolism/clearance
sends to target tissue

19
Q

Drug factors that affect dissolution rate

A

-solubility (change in Cs)
-particle size (change in A)
-pH
-types of solid (salts, hydrates, polymorphs, amorphous)

20
Q

Dosage form factors that affect dissolution rate

A

-all the listed drug factors
-disintegration rate
-excipients
-variation in manufacturing conditions

21
Q

increase solubilizing excipient use (increase Cs)

increase solubility

A

increase dissolution

22
Q

Increase surface area (A)

A

increase dissolution

23
Q

Combined effect of solubilizing excipient and particle size reduction on bioavailability

A

dissolves more quicker

24
Q

Effect of pH on solubility and dissoulution

A

low until big spike up at pH 8 (or maybe close to pka??) and as pH increases from 8 dissoultion stops and solubility levels off

25
Salt formation
-over 50% of drugs -easiest way to increase solubility
26
salt formation from acidic drug
-made by crystallizing it from a solution where pH>pKa of drug
27
salt formation from basic drug
-made by crystallizing drug in solution where pH
28
Spring and parachute effect
dissolution of salt spikes until converted to free acid then falls until leveled out to solubility of free acid SLIDE 29
29
Complexation
drug molecule forming complex with cyclodextrin molecule
30
Complexation equation
Kc = [D-CD] / [D][CD] -equilibrium
31
Cosolvents
-affects solubility in a log-linear relationship -can only change -log y part of solubility equation -moves the entire box up??
32
"brick dust" limitation
must disrupt the orderly crystal structure
33
amorphous form
-more soluble and faster dissolution -generated by getting drug into liquid form and solidifying quickly so there is no time for crystallization
34
Drugs need to be ____ in the aqueous bodily fluids in order to work
solubilized
35
drugs with ___ aqueous solubility are more the rule than the exception
low
36
Drug solubility dependent on:
1. crystallinity (brick dust) 2. hydrophobicity (wax)
37
___ impacts ____ rate but is not the only factor to do so
solubility, dissolution
38
____ is the simplest way of changing dissolution without changing solubility
Particle size
39
Solubility can be changes by:
-pH in liquid prep -pH through salt formation in solids -complexation -cosolvents
40
For really stubborn “brick dust” drugs or when hitting the brick wall with cosolvents, disrupting the ___________ becomes necessary
crystal (amorphous formulations)