Exam 1 Definitions/Learning Objectives Flashcards
1
Q
What are 3 types of liquid dosage forms?
A
Solution
Emulsion
Suspension
2
Q
What is the definition of a solution?
A
A homogeneous molecular dispersion
3
Q
What is the definition of an emulsion?
A
System of 2 immiscible liquids where one is dispersed as droplets
Oil in water, water in oil
4
Q
What is the definition of a suspension?
A
Solid in water or oil
5
Q
What are 3 advantages of Solution dosage forms?
A
Homogeneous- No content uniformity issues
Good bioavailability
Easy to manufacture
6
Q
What are the 6 components of a solution?
A
Active ingredient Solvent Buffer Preservative Antioxidant- Chelating agent Flavor/sweeteners
7
Q
What is the definition of a buffer?
A
A solution of a weak acid and the salt of its conjugate base
8
Q
What is the function of the weak acid component in a buffer?
A
It removes the added base (OH-)
9
Q
What is the function of the salt component in the buffer?
A
It removes the added acid (H+)
10
Q
What is the definition of buffering capacity?
A
The ability of buffer to resist a change in pH due to addition of acid or base
11
Q
What does C stand for in the buffering capacity equation?
A
C= Total buffer concentration
C = [HA] + {A-]
12
Q
What are 4 common buffers?
A
Citric acid
acetic acid
glycine
phosphoric acid
13
Q
What are 2 things to keep in mind when selecting a buffer?
A
- Use a pH that provides maximum drug stability
2. Minimize irritation by making pH equal to that of the body fluid
14
Q
What are 3 things you can do to minimize irritation when the pH cannot be matched to the surrounding fluid?
A
- Minimize buffering capacity
- Reduce volume
- Administer slowly
15
Q
What is the purpose of antimicrobial preservatives?
A
- Protects the patient from pathogens
2. Maintains the potency and stability of dosage forms
16
Q
What is the mechanism behind antimicrobial preservatives?
A
Adsorb to the bacterial membrane and disrupt it- often lyse the bacteria or prevent proliforation
17
Q
What are the properties of the bacterial membrane that preservatives use to bind?
A
The negatively charged surface membrane and the lipophilicity of the membrane allows for hydrophobic interactions
18
Q
Which antimicrobial preservatives use the lipid solubility to bind?
A
Alcohols, acids, esters
19
Q
Which antimicrobial preservatives use the electostatic interactions to bind?
A
Quaternary ammonium compounds
20
Q
How much bacterial content is allowed in ampules- injectable solutions?
A
None, solution must be sterile
For single dose vials no preservative is needed
21
Q
How much bacterial content is allowed in multiple dose vials?
A
None, must be sterile
May contain up to 10 doses, require preservatives
22
Q
How much bacterial content is allowed in opthalmic solutions?
A
None, must be sterile
Must contain a preservative if packaged in a multiple dose container
23
Q
How much bacterial content is allowed in oral liquids?
A
Less than 100 pathogens/1 mL
Need preservatives for multiple dose packages
24
Q
How much bacterial content is allowed in oral solids?
A
Less likely to carry bacteria than liquid forms
Can be contaminated with salmonella
Check raw materials and make sure facility is clean
25
Characteristics of ideal preservatives?
1. Effective in low concentrations against a wide variety of organisms
2. Soluble in formulation
3. Non toxic
4. Stable
26
List 5 pharmaceutical preservatives?
1. Alcohols
2. Acids
3. Parabens
4. Quaternary Ammonium Compounds
27
Characteristics of ethanol as a preservative?
Requires a concentration of greater than 15 percent
oral products only
can be lost because it is so volatile
28
Characteristics of Benzyl Alcohol as a preservative?
```
Local anethetic action
Burning taste- not used orally
Water soluable
Stable over wide pH range
Highly used in parenterals
```
29
Characteristics of acids as preservatives?
Only active in the unionized form - lipid soluable because they have more affinity for the microbial membrane
30
What products are Benzoic acid utilized in?
Oral products
31
What products are Sorbic acid utilized in?
Oral products (excellent for molds/yeast)
32
Characteristics of Parabens as preservatives?
Widely used orally
Lipophillic and less lipophillic varieties (depends on length of hydrocarbon R group)
low soluability
Can cause skin sensitization when used dermatologically
33
What factors effect the action of preservatives?
```
pH (ionized vs. unionized acids)
Complex formation (can't be used when complexed)
Adsorption by solids
Chemical stability (shelf life)
```
34
How can oxidation be prevented?
Add excipients
35
What excipients can be used to prevent oxidation?
Vitamins, essential oils, fats, oils
36
What are the 2 kinds of oxidation?
Auto- Oxidation (spontaneous)
| heat/light/metal/peroxide initiated (creates free radicals)
37
What are the 3 kinds of antioxidants?
Free radical scavengers
reducing agents
chelating agents
38
Mechanism for Free radical scavengers?
Retard/delay oxidation by rapildy reacting with free radicals
39
Mechanism for reducing agents?
Lower redox potential than the drug so it is more readily oxidized
40
Mechanism for chelating agents?
antioxidant syngergists, remove trace minerals
41
What are the 2 phases of an emulsion?
dispersed phase
| continuous phase
42
What properties of the emulsion does the continuous phase dictate?
the organoleptic properties
| taste, smell, feel
43
What forms can an emulsion come in?
oral, external, IV
44
Can oils be injected IV?
Yes- if can make it as an emulsion
45
How are forces dispersed in the bulk phase of an emulsion?
Molecules are all attracted to each other equally in all directions
46
How are forces dispersed at the boundary phase of an emulsion?
Forces are unequal, molecules all exhibit different forces
| water- H bond, oil- london dispersion forces
47
What is interfactial tension?
Caused by the imbalance between force dispersion between the bulk phase and the boundary phase
- result is constant spontaneous mvmt between phases and fewer molecules at the interface per unit area
- increasing the area of contact btw the 2 phases creates tension
- ** the force of this tension per unit length of interface is Interfacial tension
48
What kind of tension is interfacial tension?
Liquid- liquid
49
What kind of tension is Surface tension?
liquid- air tension
50
What increases interfacial tension?
Stronger intermolecular forces in the bulk phase
| intermolecular forces are reduced at high temp
51
What are the 3 types of emulsifying agents?
Surfactive agents
hydrophilic colloids
finely divided solid particles
52
What class does surfactants fall into, amphiphillic, hydrophillic or hydrophobic?
Amphiphillic
53
What affect does high surfactant concentration have on surface tension>
it reduces surface tension (to a certian point- critical micelle concentration)
54
What is hydrophile-lipophile balance (HLB)?
A measure of the relative contributions of the hydrophillic and lipophillic regions of a surfactant
- ranges from 0-20 for nonionic surfactants
55
Low HLB = ______ lipid solubility?
Greater
56
What does "a" stand for in the HLB equation?
"a"= fraction of surfactant 1 in the surfactant mixture
57
What happens when the surfactant concentration increases above the critical micelle concentration?
The surfactant molecules self associate into micelles
58
What emulsions are hydrophilic colloids used in?
O/W emulsions
59
How do hydrophilic colloids work?
They increase the viscocity of water and form a multimolecular film on the surface
60
Do hydrophilic colloids lower interfacial tension?
NO
61
How do finely divided solid particles work?
They adsorb at the interface and form a film of particles
| Hydrophilic and hydrophobic forms
62
HLB greater than 10
W/O
63
HLB less than 10
O/W
64
When is a finely divided solid particle hydrophillic?
if the contact angle is less than 90 degrees
| O/w
65
When is a finely divided solid particle hydrophobic?
if the contact angle is greater than 90 degrees
| W/O
66
What is the Phase volume ratio?
Volume of Oil phase/Total volume of the emulsion
67
Phase volume ratio of 0-26%?
O/W
68
Phase volume ratio of 26-74%?
Either O/W or W/O
69
Phase volume ration of 74-100%?
W/O only
70
What 3 ways can an emulsion become unstable>
1. Creaming
2. Coalescence
3. Phase inversion
71
Stokes Law: What does V stand for?
V= velocity of sedimentation
(-) = floating droplets
high IvI- settles or floats frequently
72
Stokes Law: What does d stand for?
d= diameter of the droplets
73
Stokes Law: What does Pi stand for?
Pi = density of the internal phase
74
Stokes Law: What does Pe stand for?
Pe= Density of the external phase
75
Stokes Law: What does n stand for?
n = viscosity of the external phase
76
Is creaming reversible?
Yes, as long as the interfacial film is effective in maintaining the integrity of the individual droplets
77
Is coalescence reversible?
NO, leads to a layer of oil and water- broken
| can't fix by shaking
78
What causes phase inversion?
a phase volume ration of greater than 74%
| hard water can cause it also
79
When making an emuslion, do the aqueous solution and oil solution need to be heated to the same temperature to mix?
Yes, then cooled slowly and passed through a homogenizer
80
What is a suspension?
Liquid preparation where solid particles are dispersed through a liquid phase in which the particles are not soluble.
81
Advantages for suspensions?
```
Solubility
Chemical Stability
Taste/Palatability
Dose is flexible
Faster Dissolution than tablets
```
82
What is the kinetic order of solutions?
1st order (fast)
83
What is the kinetic order if suspensions?
Second order (slower rxn, faster dissolution and more bioavilability)
84
What are the components of a suspension?
```
Active ingredient
Vehicle
Buffer
Preservative
Flocculating agent
Structured vehicle system
wetting agent
antifoming agent
flavor/sweetener
```
85
Required characteristics of a suspension?
Suspended particles should settle slowly
Particles that settle should be able to re-disperse
The suspension must flow but not to much
Particle size must remain constant
86
Stokes Law: Ps
Ps = density of solid
87
Stokes Law: Pl
Pl = density of liquid
88
Micropulveration
10-50um
| Most oral and suspensions
89
Fluid Energy Grinding
<10 um
Parenteral and opthalmic suspensions
Shearing action of high velocity air
90
Spray drying
<5umn
| Solution of drug is sprayed and dried by air
91
what are the 3 types of suspensions?
dispersed suspension
flocculated suspension
structured vehicle system
92
DeltaG = ?
Increased surface free energy
| suspension is stable when G = 0
93
Ys/l = ?
Interfacial tension between solid and liquid
94
DeltaA = ?
increase in surface area
| want small particles--> high deltaA
95
What 2 forces decrease particle size?
aggregation
| crystal growth
96
Van der Waals forces, attractive or repulsive?
attractive, over moderate distances but gets very strong close to the surface
not affected by formulation factors
97
Electrostatic forces, attractive or repulsive?
Repulsive, due to the surface charge on the particle
| Can be affected by formulation
98
Steric forces, attractive of repulsive?
Repulsive
| can be controlled by the formulation
99
Hydration forces, attractive or repulsive?
Repulsive
| not affected by formulation
100
Net effect of interparticle forces?
```
Repulsive force (+) little effect when particles are far apart
Attractive force (-) dominant when particles are close
```
101
Dispersed suspension what forces are dominant?
Repulsive
Particles repel each other and don't aggregate
particles settle and are difficult to re-suspend
102
Controlled flocculation what forces are dominant?
Repulsive and attractive forces are balanced
103
How does a flocculated suspension work?
At the secondary minimum the repulsive force is reduces a bit
when floccules settle, they are easy to re-disperse
104
What type of sediment does a flocculation form?
High volume
105
What are some examples of flocculating agents?
Clay
pH manipulation
Electrolytes
Non-ionic/ionic surface active agents
106
What type of suspensions is clay used in?
Oral suspensions
107
What type of suspension will you alter the pH in?
parenteral solutions
108
How do electrolytes create flocculations?
Reduces the electrical barrier between particles
| only works at ideal concentration
109
Structured Vehicle system
Thickens the dispersion medium to suspend the particles
110
Does the structured vehicle interfere with the availability of the drug?
NO
111
What are 2 types of structured vehicles?
Clay
| polymers
112
Rheology
The study of flow characteristics
113
What is shear rate?
dv/dr
| the difference of velocity (dv) between 2 planes of a liquid separated by a distance (dr)
114
What is shear stress?
F
| the force per unite area required to bring about flow
115
What are the 2 kinds of shear stress?
Newtonian flow
| non-newtonian flow
116
What are the 3 kinds of non-newtonian flow?
Plastic
Pseudoplastic
Dilatant
117
what is the shape of a newtonian flow curve?
Linear
| slope is constant at all shear stress
118
What is the shape of a plastic flow curve?
liquid doesn't flow until a certian shear stress is reached
119
What is the shape of a pseudoplastic curve?
high force = high flow
120
WHat is the shape of a dilatant curve?
high force = low flow
121
What is f( yield value) mean?
Threshold of shear stress necessary to initiate flow
122
Shear thinning
The strength of the attractive force of the secondary minimum
123
Pseudoplastic suspensions?
No stress
typical polymer
Shear thinning
124
Thixotropy
the ability of the system that was disturbed by an applied shear stress to return to the undisturbed structure
125
Which kinds of rheology suspensions exhibit thixotropy?
plastic and pseudoplastic
126
What does thixtropic suspensions form at rest?
A rigid gel matrix to stabilize the suspensions (shear stress from shaking makes it more liquid)
127
Is there sedimentation with a structures vehicle suspension?
NO
128
What is wetting?
displacement of air from the surface of a particle by the vehicle
129
What does contact angle have to do with wetting?
High angle indicates poor spreading
130
What is the importance of a wetting agent?
for rough particles, an aqueous vehicle will not enter the pores and the particle will float due to the high air content
- wetting gent reduces the surface tension of the aq vehicle to allow water to enter the pore
