Solutions Flashcards
1
Q
True or false: suspensions are a heterogenous mixture
A
false
2
Q
What is a pharmaceutical solution?
A
a chemically and physically homogenous liquid preparations of two of more substances
3
Q
What is the difference between a solute and solvent?
A
solute: the substance that dissolves
solvent: substance in which the solute is dissolved
4
Q
What is the universal solvent?
A
water
5
Q
Aside from water, what are other solvents used in pharmacy?
A
alcohol (diluted alcohol, dehydrated alcohol, rubbing alcohol)
isopropyl alcohol
glycerin
propylene glycol
polyethylene glycol 400
6
Q
What is the strength of polyethylene glycol you would use for a solution?
A
400
-anything higher will turn the product into a solid
7
Q
When you hear “alcohol” in pharmacy, what is this referring to?
A
ethanol
8
Q
What are examples of solvents used pharmaceutically in processing drug products, for assays and tests or for making specialty products?
A
acetone
ether
chloroform
9
Q
True or false: oils can be used as pharmaceutical solvent-vehicles
A
true
10
Q
What are a few examples of dosage forms utilizing solutions?
A
injectables
pediatric formulations
ophthalmic preparations
ear drops
some lotions
11
Q
What are advantages of pharmaceutical solutions?
A
can be intended for multiple routes of administration
drug available for absorption
flexible dosing
no shaking of solutions needed (complete dissolution)
12
Q
What are disadvantages of pharmaceutical solutions?
A
drug stability may be compromised
technical accuracy or delivery devices needed for dose accuracy
solubility properties of drug must be matched with excipients
bulky storage and transportation
13
Q
What is the difference between solubility and dissolution?
A
solubility: quantity of solute that will dissolve in a specified quantity of solvent
-the extent to which a solute dissolves
dissolution: the transfer of molecules and ions from a solid phase into a solution
-process by which a drug particle dissolves
SOLUBILITY IS A PROPERTY, DISSOLUTION IS A PHENOMENON/PROCESS
14
Q
What is involved in the phenomenon of dissolution?
A
removal of a molecule of a drug from the solid state
formation of a cavity within the solvent
accommodation of the drug molecule into the formed cavity
breakage of solute-solute bonds and solvent-solvent bonds and the formation of a bond between solute and solvent
15
Q
What is the general rule in regards to solubility and dissolution?
A
the more soluble the drug, the faster the dissolution into the solvent
16
Q
What are ways to enhance dissolution?
A
triturating to reduce particle size and decrease the solution time
sometimes heat can enhance dissolution
sometimes vigorous shaking or stirring is required
17
Q
USP defines solubility as the # of mls of solvent in which 1g will dissolve, what does this tell us about solubility when ml is high or low?
A
high ml (volume): low solubility
low ml (volume): high solubility
18
Q
What are the factors affecting solubility?
A
molecular weight, volume
presence of functional groups
acids or bases
19
Q
An aqueous solution has a ____ boiling point and a ____ freezing point than does pure water.
A
higher boiling point
lower freezing point
20
Q
What happens to boiling point and melting point when the amount of solute increases?
A
boiling point increases
melting point decreases
21
Q
True or false: increasing temperature decreases solubility of solids
A
false
increasing temperature increases solubility of solids
22
Q
What are the types of solutions?
A
gases in liquids
liquids in liquids
solids in liquids
23
Q
What happens to the solubility of gas in liquid when pressure increases?
A
solubility of gas increases
24
Q
What happens to the solubility of gas in liquid when temperature increases?
A
solubility of gas decreases
25
What determines the amount of gas that will dissolve in a liquid?
pressure
temperature
26
What is miscibility?
expresses the mutual solubility of components in a liquid-liquid system (mixes without seperating)
27
What are the types of liquid pairs?
soluble in all proportions
-ex: alcohol and water or glycerin and water
soluble in definite proportions
-ex: phenol and water, mutual solubility is influenced by temperature
-when temperature increases, miscibility is altered
28
What are the factors affecting solubility of solids in liquids?
temperature
pharmaceutical solvents
mixed solvents
complexation
29
Explain what happens if a drug is endothermic.
solubility increases with increased temperature
positive heat of solution
the solution process requires the input of energy, or heat is absorbed when the solute is dissolving (e.g. syrup)
30
Explain what happens if a drug is exothermic.
solubility decreases with increased temperature
negative heat of solution
in the solution process heat is given off when the solute is dissolving (e.g. NaOH dissolving in water)
31
Explain what happens if a drug is normothermic.
heat is neither absorbed nor given off during the solution process (e.g. KCl)
32
True or false: solubility does not depend on temperature
false
33
What are the two types of pharmaceutical solvents?
polar
non-polar
34
What is polarity?
separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a positively charged end and negatively charged end
35
What are some examples of substances with small or no dipolar characteristics?
fixed oils
hydrocarbons
36
What are the uses of substances with small or no dipolar characteristics?
vehicle for injections
external preparations
37
What is potable water?
water that is fit to drink
found in rivers, lakes, wells, and springs
dissolves material from natural contacts and contains salts of:
-Ca, Mg, Fe, K, Na
-organic matter
-atmospheric gases
-suspended materials (clay, sand)
38
How do you render potable water?
removal of insoluble matter by settling and filtration
destruction of pathogenic organisms by chlorination
on a small scale:
-boiling for 15-20 minutes and treating with a chlorinating
agent
39
What is the percentage of solids in potable water?
<0.1%
40
Why does tap water not meet the standards in dosage forms?
can result in chemical incompatibilities
-precipitate
-discoloration
-effervescence
41
True or false: sterile preparations for multi-dose need a preservative agent
true
42
What are other "forms" of water used in preparations?
purified water-dilution for non-sterile preparations
water for injection-sterile preparations
sterilized water
bacteriostatic water for injection-multi dose sterile preparations
43
What are examples of semi-polar solvents used as the primary solvent for many organic compounds?
alcohol
isopropyl alcohol
glycerin
propylene glycol
polyethylene glycol 400
44
What is the most common solvent?
alcohol
45
What is an elixir?
alcohol + water=hydro alcoholic solution
-dissolves both alcohol and water-soluble components
46
What are the advantages of semi-polar solvents?
better solubility for many compounds
can be used as co-solvent
better stability for the drug
-decreased hydrolysis
-decreased bacterial growth
miscible with a wide range of solvents
-caster oil
-water
-other semi-polar solvents
47
What are the limits for alcohol in OTC products?
children <6: <0.5%
children 6-12: <5%
adults: <10%
48
What are the different types of alcohol?
denatured: has additives (ketones or kerosene) to render it
more poisonous and unfit for internal use
absolute (100%): 99.5% ethanol, essentially water-free
diluted: diluting alcohol with an equal volume of purified water
-alcohol concentration of 49%
-useful as hydro alcoholic solvent in preparations
rubbing alcohol: 70% by volume, antiseptic, external use only
49
What are miscible solvents?
a solute may be more soluble in a mixture of solvents than in one solvent=co-solvent effect
50
What should be done when there are two or more solvents and two or more solutes in a formulation?
Each solute should be dissolved in the solvent in which it is most soluble before mixing with other liquids in the preparation
51
What are complexes?
Loose molecular associations that can either increase or decrease solubility
52
What is an example of a complex?
Tetracycline: complexes with calcium in milk to form an insoluble complex that decreases the drugs dissolution and absorption
53
What is an important counselling with point tetracycline?
Avoid milk or dairy within 2 hours of taking tetracycline
54
Calcium and iron should be avoided with what?
Certain antibiotics (demeclocycline,tetracycline, ciprofluxacin,norfloxacin)
Certain medications for osteoporosis (risedronate)
Thyroid medication (levothyroxine)
55
When stirring a solution, how can you improve solubility?
Stirring
elevated temperature
Reduction of particle size
salt form rather than base form
Sometimes: mixed solvent system
56
What are the many ways to express drug concentration in a solution?
Molarity (M): mol/L
Molality (m): mol/kg
Osmolarity (osmol): osmol/L (# of moles contributing to osmotic pressure of the solution)
Units of potency/unit volume (IU): IU/L
Weight/unit volume: g/L, mg/ml
Percentage strength: w/v, v/v, w/w, mg%,ug%
Parts per million: ppm
57
Solutions for oral administration often stained additives, why?
Storage stability,enhance solubility, taste
58
What are convenient volumes of solution per close?
drops
5ml (1 tsp)
10ml (2tsp)
15ml (1tbsp)
59
What are requirements in the preparation of clan solutions?
Physical stability
Chemical stability
Microbiological stability
Palatability
Pleasing appearance
60
What are characteristics of stability that can be seen or felt?
No discoloration/cloudiness
no precipitation
no loss of elegance
no loss of taste
61
When controlling chemical stability of solutions, what are some properties that must be controlled for?
pH (use of buffers)
Hydrolysis and oxidation
-hydrolysis controlled by using non-aqueous solvents
-oxidation controlled by antioxidants
62
How is microbial stability controlled in solutions?
Solvents with preservative action (ex: >20% glycerin, alcohol)
63
How is palatability controlled in solutions?
Sweeteners: sucrose, sorbitol
Flavours
64
How do we improve appearance of solutions?
Add colours or viscosity inducing agents
65
What are characteristics of ideal additives?
Inactive and non-toxic
Potent, therefore can be used in low concentrations
No unpleasant odouor flavour
Compatible with drug and other excipients
Stable to changes ph or light exposure and heat
Soluble in the vehicle/solvent
66
What are the additives for oral solutions?
Flavouring agents
Sweeteners
Colouring agents
Antimicrobial preservatives
Antioxidants
Buffers
Viscosity-inducing agents
Surface active agents
67
What are the four primary tastes?
Sweet
Sour
Bitter
Salty
68
Which molecules are required for the sensation of each taste?
Sweet: low molecular weight poly-hydroxyl ' compounds (sucrose, sorbitol, mannitol)
Sour: result of H+ ions
Bitter: high molecular weight salts, free bases, nitrogen containing compounds
Salty: low molecular weight salts and ionic compounds
69
How does physiological flavouring technique work?
Anesthetize the taste buds/receptors
ex: menthol, mint flavours, carbonated beverages, ice cube on tongue
70
How does the physical flavouring technique work?
Prevent dissolution of drug (prevent it from coming in contact with taste buds)
-use of viscous fluids
- formulate an emulsion
-coating tablets
71
How does the overshadowing flavouring technique work?
Addition of a flavour whose intensity is longer and stronger than the taste of the drug
72
How does the blending flavouring technique work?
Add flavours which compliment the taste and modify the flavour perception
-sour taste: blended with fruit flavours
-bitter taste: adding salty, sweet and sour flavour
73
What are other flavouring factors, beside taste?
aroma (strong determinant of taste perception)
texture
viscosity of syrups (less viscous: perception of watered down, too viscous: slimy, gooey)
74
What are the two categories of sweeteners?
natural sweeteners (sugars and polyols)
artificial sweeteners
75
What are the desired properties of sweeteners?
colourless
odourless
solubility in water at the concentration needed for sweetening
pleasant tasting
no aftertaste
stable over a wide pH range
76
Describe sucrose as a sweetener.
sucrose (cane sugar, beet sugar)
-disaccharide (glucose, fructose)
-385 calories/100g (4cal/g)
-standard for sweeteners (other sweeteners are compared to
sucrose)
77
What are the concerns of using sucrose as a sweetener?
high water solubility, but may reduce water solubility of other solutes
may pose a problem for diabetics
has a tendency to crystallize on the threads of bottle caps
inversion & caramelization
78
Describe lactose as a sweetener.
lactose (milk sugar)
-disaccharide (galactose, glucose)
-less sweet than sucrose (usually used as an inert filler rather
than as a sweetener)
-many people are lactose intolerant
79
Describe dextrose as a sweetener.
dextrose (glucose, corn syrup)
-monosaccharide
-less sweet than sucrose
-generally not used in oral products but sometimes as IV
80
What are examples of artificial polyols?
glycerine
propylene glycol
-they are liquids primarily used as co-solvents but also
contribute to the sweetness of the product
-less sweet than sucrose
-fewer calories than sucrose
81
What are examples of natural polyols? Describe them.
sorbitol
-2.6cal/g, more slowly absorbed
-less sweet than sucrose (0.6x sucrose)
-can cause gas/flatulence
mannitol
-half the caloric value of sucrose
-less sweet than sucrose (0.5x sucrose)
-high intake has laxative effects
xylitol
-equal sweetness to sucrose but absorbed more slowly
-negligible affect on blood sugar
-more expensive than sucrose
82
True or false: artificial sweeteners have caloric value
false
83
What are all the artificial sweeteners?
saccharin
cyclamate
aspartame
sucralose
stevia
84
Describe saccharin as an artificial sweetener.
300 times sweeter than sucrose
often used as its sodium salt because of its better water solubility
bitter, metallic after taste
controversy over safety
85
Describe cyclamate as an artificial sweetener.
30 times sweeter than sucrose
objectionable taste when used alone, synergizes other sweeteners
used as either sodium or calcium salt
controversy and concern over safety (Canada: drugs only, not food)
86
Describe aspartame as an artificial sweetener.
non-carbohydrate nutritive sweetener
dipeptide (1 aspartic acid + 1 phenylalanine)
180 times sweeter than sucrose
4cal/g
87
What are adverse reactions that aspartame can cause?
seizures
headache
88
When would it not be acceptable to use aspartame as a sugar subsititute?
when high temperature will be used in processing
-aspartame degrades into diketopiperazone at high temp
89
What is a medical condition where you should not be given aspartame?
phenylketonuria (inborn error of metabolism)
-must restrict phenylalanine intake
-accumulation of phenylalanine can cause brain damage,
seizures, severe mental retardation
90
Describe sucralose as an artificial sweetener.
600 times sweeter than sucrose
not metabolized
no bitter after taste, tastes like sugar
91
Describe stevia as an artificial sweetener.
200 times sweeter than sucrose
some aftertaste
1cal/g in blends with dextrose
drug interactions: lithium, diabetes, antihypertensives
92
Why do we use colourants in solutions?
elegance
attractiveness
sensory adjunct to flavour (enhances acceptance)
93
True or false: colourants are required in every solution preparation
false
94
What is visual distraction? When does it not work?
means of enhancing palatability by giving a bitter substance a nice colour
wont work for:
-kids that havent developped color/aroma/taste correlation
-multiple doses are required
95
What are the classes of natural colouring agents? Name examples in each class.
mineral pigments (yellow ferric oxide, white titanium oxide, red ferric oxide and carbon black)
plant pigments (green chlorophyll, orange B carotene, yellow saffron)
animal pigments (purple murex)
96
Which formulations use mineral pigments?
lotions
cosmetics
other external preparations
97
Colours used in foods, drugs, and cosmetics must be certified for use, who certifies this?
FD&C (safest)
D&C (not food)
external D&C (not allowed in lip products)
98
When are colourants never added to solutions?
ophthalmic solutions
99
What are some problems with synthetic colouring agents?
carcinogenicity probability
hypersensitivity
hyperactivity
dyes may be affected by changes in pH
may be liable to oxidation or reduction rxns
many are salts of sulfonic acids and may be incompatible with large cationic compounds such as alkaloids
100
What is the concentration of colouring agents used?
0.0005-0.001%
101
It can be difficult to maintain consistent measurements of such small amounts of dye while making the same preparation multiple times, what can be done?
make a dilutewd stock solution of the dye to consistently measure reasonable quantity like 1ml
102
When are antimicrobial preservatives added?
non-sterile dosage forms
-prevent microbial growth
-protect from organisms inadvertently added during
manufacturing
103
When do you not add preservative to solutions?
formulation is used immediately
no water is present
pH is <3 or >9 (organisms grow at 3-9)
other ingredients are antimicrobial (alcohol or sugar)
large volume parenteral
104
When are preservatives contraindicated?
neonates
ophthalmics intended for use in eye surgery
parenterals with volume >30ml
105
What are alternative strategies when preservatives are needed but contraindicated?
prepare single doses
prepare a limited quantity that will be used in a short period of time
store under refrigeration and label with BUD
106
What are the requirements of a preservative?
broad spectrum
reduce microbial pop significantly + prevent growth
107
How do antioxidants work?
provide electrons and easily available hydrogen atoms to the damaging free radicals thereby stopping propagation
-protects drug from oxidation
108
What are examples of antioxidants?
aqueous system: ascorbic acid, Na sulfite & bisulfite
oil systems: BHA, alpha-tocopherol
109
What is the job of buffers in solution?
control pH and therefore stability
contains a weak acid and its conjugate base
110
Which formulations require buffers?
formulations applied to sensitive membranes of eye or nasal passages or injected into muscles, blood, organs, tissues, or lesions
111
What is the role of viscosity-inducing agents in solutions?
used to change the consistency of a preparation to render it more resistant to flow
easier to pour
improves appearance and palatability
112
When are viscoscity inducing agents essential?
topical solutions
-acheives smoothness and consistency
-ease in applying
-remains in contact with affected area
113
How does viscosity affect dissolution?
higher viscosity=lower dissolution
114
What is the solution to viscosity lowering dissolution?
add viscosity inducer after dissolving the drug
115
What is the role of surface active agents in solutions?
modulate solubility of ingredients to improve stability and sometimes bioavailability
contain hydrophilic and hydrophobic regions
116
What is an example of a surface active agent?
sodium lauryl sulfate
117
What are syrups?
concentrated, viscous, sweetened aqueous solutions that may contain less than 10% alcohol
concentrated or nearly concentrated saturated solution of sugar (usually sucrose) or sugar substitute in water
-with or without flavouring agents
-with or without medicinal substances
118
What are sugars other than sucrose that can be used to prepare syrups?
non-sugar polyols (sorbitol, glycerin, propylene glycol, mannitol)
non-nutritive artificial sweeteners (aspartame, saccharin)
119
When must antimicrobial preservatives be added to syrups?
sucrose content of syrup is <80%
120
What are flavouring syrups?
flavouring vehicles
they are vehicles only and do not contain drug
used in compounding
121
What is always added to syrups?
colorant to enhance appeal of the syrup
-most correlated with flavour, NOT ALWAYS
122
What must be determined before using a flavored syrup?
determine if its acidic, basic, or neutral and whether this will cause a problem with the stability of the added medicinal agent
123
Describe simple syrup.
saturated solution of sucrose in water
85% w/v or 65% w/w
sucrose 850g + purified water qs ad 1000ml
fully saturated and self-preservative
if diluted, it will support mold and other microbial growth
124
How do we correctly compound when dealing with syrups?
drug is dissolved in water or another solvent before mixing with the syrup vehicle
-prevents precipitation
125
What are aromatic waters?
clear, saturated aqueous solutions of volatile oils or another aromatic substances
-peppermint water, stronger rose water
used as flavouring or perfuming solutions
126
How is aromatic water made?
volatile oil + 15g of talc +1000ml of purified water
thoroughly agitate for 30 minutes
filtration is performed
127
What is the role of talc in compounding an aromatic water?
distribution agent
-increases surface area of the volatile substance that is
exposed to water and to facilitate the saturation of the
solution with oil
filter aid
-remove excess volatile agent
128
What are the solvents used in non-aqueous solutions?
solvents other than water, either alone or in addition to water
internal use: glycerin, alcohol, propylene glycole
129
What are examples of non-aqueous solutions?
elixirs
spirits
tinctures (most for natural products and herbal supplements)
130
What are elixirs?
clear, sweetened hydro alcoholic solution for oral use
131
What is the range of sugar in elixirs?
3-44%
*MOSTLY BETWEEN 5-10%*
132
When must you add preservative to elixirs?
if there is less than 10-12% alcohol
133
Compare elixirs to syrups based on sweetness, viscosity, masking bitter taste of drug, maintaining water and alcohol soluble components, stability, storage
less sweet
less viscous
less effective in masking drug taste
more able to maintain water and alcohol soluble components
more long-term stability
more strict storage conditions due to alcohol
134
Describe spirits.
alcoholic or hydro alcoholic solutions of volatile substances
alcohol content range: 62-85%
used as flavouring agents in small quantities
maintain a greater concentration of volatile oils than aromatic water
135
Describe tinctures.
alcoholic or hydro alcoholic solutions of non-volatile substances prepared from vegetable or chemical substances
alcohol content: 15-80%
must not be exposed to high temperature
oil content up to 50%
136
Why are tinctures no longer prescribed?
high alcoholic content
137
True or false: tinctures can be mixed successfully with liquids
false
cannot be mixed successfully with liquids too diverse in solvent character without inducing precipitation of the solute
138
What are the advantages of reconstituted solutions?
extended shelf-life
reconstituted as a solution by adding solvent before dispensing
once reconstituted, shelf-life of 7-14 days
