Solutions Flashcards
True or false: suspensions are a heterogenous mixture
false
What is a pharmaceutical solution?
a chemically and physically homogenous liquid preparations of two of more substances
What is the difference between a solute and solvent?
solute: the substance that dissolves
solvent: substance in which the solute is dissolved
What is the universal solvent?
water
Aside from water, what are other solvents used in pharmacy?
alcohol (diluted alcohol, dehydrated alcohol, rubbing alcohol)
isopropyl alcohol
glycerin
propylene glycol
polyethylene glycol 400
What is the strength of polyethylene glycol you would use for a solution?
400
-anything higher will turn the product into a solid
When you hear “alcohol” in pharmacy, what is this referring to?
ethanol
What are examples of solvents used pharmaceutically in processing drug products, for assays and tests or for making specialty products?
acetone
ether
chloroform
True or false: oils can be used as pharmaceutical solvent-vehicles
true
What are a few examples of dosage forms utilizing solutions?
injectables
pediatric formulations
ophthalmic preparations
ear drops
some lotions
What are advantages of pharmaceutical solutions?
can be intended for multiple routes of administration
drug available for absorption
flexible dosing
no shaking of solutions needed (complete dissolution)
What are disadvantages of pharmaceutical solutions?
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
What is the difference between solubility and dissolution?
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
What is involved in the phenomenon of dissolution?
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
What is the general rule in regards to solubility and dissolution?
the more soluble the drug, the faster the dissolution into the solvent
What are ways to enhance dissolution?
triturating to reduce particle size and decrease the solution time
sometimes heat can enhance dissolution
sometimes vigorous shaking or stirring is required
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?
high ml (volume): low solubility
low ml (volume): high solubility
What are the factors affecting solubility?
molecular weight, volume
presence of functional groups
acids or bases
An aqueous solution has a ____ boiling point and a ____ freezing point than does pure water.
higher boiling point
lower freezing point
What happens to boiling point and melting point when the amount of solute increases?
boiling point increases
melting point decreases
True or false: increasing temperature decreases solubility of solids
false
increasing temperature increases solubility of solids
What are the types of solutions?
gases in liquids
liquids in liquids
solids in liquids
What happens to the solubility of gas in liquid when pressure increases?
solubility of gas increases
What happens to the solubility of gas in liquid when temperature increases?
solubility of gas decreases
What determines the amount of gas that will dissolve in a liquid?
pressure
temperature
What is miscibility?
expresses the mutual solubility of components in a liquid-liquid system (mixes without seperating)
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
What are the factors affecting solubility of solids in liquids?
temperature
pharmaceutical solvents
mixed solvents
complexation
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)
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)
Explain what happens if a drug is normothermic.
heat is neither absorbed nor given off during the solution process (e.g. KCl)
True or false: solubility does not depend on temperature
false
What are the two types of pharmaceutical solvents?
polar
non-polar
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
What are some examples of substances with small or no dipolar characteristics?
fixed oils
hydrocarbons
What are the uses of substances with small or no dipolar characteristics?
vehicle for injections
external preparations
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)
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
What is the percentage of solids in potable water?
<0.1%
Why does tap water not meet the standards in dosage forms?
can result in chemical incompatibilities
-precipitate
-discoloration
-effervescence
True or false: sterile preparations for multi-dose need a preservative agent
true
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
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
What is the most common solvent?
alcohol
What is an elixir?
alcohol + water=hydro alcoholic solution
-dissolves both alcohol and water-soluble components
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
What are the limits for alcohol in OTC products?
children <6: <0.5%
children 6-12: <5%
adults: <10%
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
What are miscible solvents?
a solute may be more soluble in a mixture of solvents than in one solvent=co-solvent effect
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
What are complexes?
Loose molecular associations that can either increase or decrease solubility
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
What is an important counselling with point tetracycline?
Avoid milk or dairy within 2 hours of taking tetracycline
Calcium and iron should be avoided with what?
Certain antibiotics (demeclocycline,tetracycline, ciprofluxacin,norfloxacin)
Certain medications for osteoporosis (risedronate)
Thyroid medication (levothyroxine)
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
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
Solutions for oral administration often stained additives, why?
Storage stability,enhance solubility, taste
What are convenient volumes of solution per close?
drops
5ml (1 tsp)
10ml (2tsp)
15ml (1tbsp)
What are requirements in the preparation of clan solutions?
Physical stability
Chemical stability
Microbiological stability
Palatability
Pleasing appearance
What are characteristics of stability that can be seen or felt?
No discoloration/cloudiness
no precipitation
no loss of elegance
no loss of taste
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
How is microbial stability controlled in solutions?
Solvents with preservative action (ex: >20% glycerin, alcohol)
How is palatability controlled in solutions?
Sweeteners: sucrose, sorbitol
Flavours
How do we improve appearance of solutions?
Add colours or viscosity inducing agents
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
What are the additives for oral solutions?
Flavouring agents
Sweeteners
Colouring agents
Antimicrobial preservatives
Antioxidants
Buffers
Viscosity-inducing agents
Surface active agents
What are the four primary tastes?
Sweet
Sour
Bitter
Salty
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
How does physiological flavouring technique work?
Anesthetize the taste buds/receptors
ex: menthol, mint flavours, carbonated beverages, ice cube on tongue
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
How does the overshadowing flavouring technique work?
Addition of a flavour whose intensity is longer and stronger than the taste of the drug
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
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)
What are the two categories of sweeteners?
natural sweeteners (sugars and polyols)
artificial sweeteners
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
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)
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
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
Describe dextrose as a sweetener.
dextrose (glucose, corn syrup)
-monosaccharide
-less sweet than sucrose
-generally not used in oral products but sometimes as IV
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
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
True or false: artificial sweeteners have caloric value
false
What are all the artificial sweeteners?
saccharin
cyclamate
aspartame
sucralose
stevia
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
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)
Describe aspartame as an artificial sweetener.
non-carbohydrate nutritive sweetener
dipeptide (1 aspartic acid + 1 phenylalanine)
180 times sweeter than sucrose
4cal/g
What are adverse reactions that aspartame can cause?
seizures
headache
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
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
Describe sucralose as an artificial sweetener.
600 times sweeter than sucrose
not metabolized
no bitter after taste, tastes like sugar
Describe stevia as an artificial sweetener.
200 times sweeter than sucrose
some aftertaste
1cal/g in blends with dextrose
drug interactions: lithium, diabetes, antihypertensives
Why do we use colourants in solutions?
elegance
attractiveness
sensory adjunct to flavour (enhances acceptance)
True or false: colourants are required in every solution preparation
false
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
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)
Which formulations use mineral pigments?
lotions
cosmetics
other external preparations
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)
When are colourants never added to solutions?
ophthalmic solutions
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
What is the concentration of colouring agents used?
0.0005-0.001%
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
When are antimicrobial preservatives added?
non-sterile dosage forms
-prevent microbial growth
-protect from organisms inadvertently added during
manufacturing
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
When are preservatives contraindicated?
neonates
ophthalmics intended for use in eye surgery
parenterals with volume >30ml
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
What are the requirements of a preservative?
broad spectrum
reduce microbial pop significantly + prevent growth
How do antioxidants work?
provide electrons and easily available hydrogen atoms to the damaging free radicals thereby stopping propagation
-protects drug from oxidation
What are examples of antioxidants?
aqueous system: ascorbic acid, Na sulfite & bisulfite
oil systems: BHA, alpha-tocopherol
What is the job of buffers in solution?
control pH and therefore stability
contains a weak acid and its conjugate base
Which formulations require buffers?
formulations applied to sensitive membranes of eye or nasal passages or injected into muscles, blood, organs, tissues, or lesions
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
When are viscoscity inducing agents essential?
topical solutions
-acheives smoothness and consistency
-ease in applying
-remains in contact with affected area
How does viscosity affect dissolution?
higher viscosity=lower dissolution
What is the solution to viscosity lowering dissolution?
add viscosity inducer after dissolving the drug
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
What is an example of a surface active agent?
sodium lauryl sulfate
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
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)
When must antimicrobial preservatives be added to syrups?
sucrose content of syrup is <80%
What are flavouring syrups?
flavouring vehicles
they are vehicles only and do not contain drug
used in compounding
What is always added to syrups?
colorant to enhance appeal of the syrup
-most correlated with flavour, NOT ALWAYS
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
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
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
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
How is aromatic water made?
volatile oil + 15g of talc +1000ml of purified water
thoroughly agitate for 30 minutes
filtration is performed
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
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
What are examples of non-aqueous solutions?
elixirs
spirits
tinctures (most for natural products and herbal supplements)
What are elixirs?
clear, sweetened hydro alcoholic solution for oral use
What is the range of sugar in elixirs?
3-44%
MOSTLY BETWEEN 5-10%
When must you add preservative to elixirs?
if there is less than 10-12% alcohol
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
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
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%
Why are tinctures no longer prescribed?
high alcoholic content
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
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
