Solutions Flashcards
Define Solutions
A chemically and physically homogenous liquid preparation of two or more substances
List some characteristics of solutions
Homogenous one phase system
Uniform distribution of drug throughout the preparation
What is the most common solvent?
Water
What is possible other ingredients that may exist within a pharmaceutical solution?
Excipients
Colouring
Flavour
Presertevt
What are advantages of solutions?
Can be intended for multiple routes of administration
Oral solutions – drug available for absorption
Flexible dosing
No shaking of solutions needed (complete dissolution)
What are some disadvantages of 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 dosage forms utilizing solutions?
Injectable
Paediatric formulation
Ophthalmic preparation
What are some other solvent vehicles?
Alcohol
Isopropyl alcohol
Glycerin
Propylene glycol
PEG
Define Solubility
The quality of solute that will dissolve in a specified quantity of solvent to form a saturated solution
Define dissolution
The transfer of molecules and ions from a solid phase into a solution
What is the difference betweeen solubility and dissolution?
Solubility is a property while dissolution is a phenomenon/process
What are some thing that happen in dissolution?
The removal of a molecule of a drug from the solid state
The formation of cavity within the solvent
The accommodation of the drug molecule into the formed
The process involves the breakage of solute-solute and solvent-solvent bonds and the formation of a bond between the solute and solvent
What is the general rule with dissolution?
The more soluble the drug
The faster the dissolution into the solvent
List some ways to enhance dissolution
Some solids require triturating to reduce the particle size and decrease the solution time
Sometimes heat is required to enhance the dissolution
Some vigorous shaking or stirring is required
Describe dissolution
The process by which a drug particle dissolves
A process by which a solid of specific solubility characteristics enter into the solution
The smaller the particles the increase in
Dissolution
And
Absorption
List factors that affect solubility
Molecular weight
Volume
Presence of functional groups and their position
Acids or bases
What is difference in characteristics between aqueous solution and pure water?
Aq has higher boiling point and a lower freezing point
An increase in temp _____ solubility of solids
Increases
List the types of solutions
Gases in liquids
Liquids in liquids
Solids in liquids
Define miscibility
Expresses the mutual solubility of components in a liquid-liquid system
List the Types of liquid pairs
Soluble in all proportions
Soluble in definite proportions
List examples of soluble in all proportions (liquid pairs)
Alcohol and water
Glycerin and water
List examples of soluble in definite proportions (liquid pairs)
Phenol and water (influenced by temp)
What is an example of immiscible?
Oil and water
In Gases in liquids how does an increase in pressure affect
Increase solubility of gas in liquids
In Gases in liquids how does an increase temperature affect
Decrease solubility of gas in liquid
What are the two factors that determine the amount of gas that will dissolve in a liquid?
Temperature
Gas
List the factors affecting solubility
temperature
pharmaceutical solvents
mixed solvents
complexation
Explain how temperature affects solubility in an exothermic reaction
decrease solubility with the increase in temperature
Explain how temperature affects solubility in an endothermic reaction
increase solubility with the increase in temperature
Define endothermic
positive heat of solution
the solution process requires the input of energy or heat is absorbed when the solute is dissolving
Define exothermic
negative heat of solution
in the solution process heat is given off when the solution is dissolving
Define Normothermic
heat is neither absorbed nor given off during the solution process
Give an example of exothermic reaction
NaOH dissolving in water
Give an example of when endothermic reaction is used
creating syrups
Give an example of normothermic
KCl
What are the types of pharmaceutical solvents?
non-polar and polar
Define polarity
a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end
List the small or no dipolar characteristics
fixed oils - non volatile
hydrocarbons
List the uses of non polar solvents
vehicle for injections
external preparations
Explain of polar solvent
potable water
What is the natural salts in potable water?
Ca, Mg, Fe, K & Na
organic matter
atmospheric gases
suspended materials
Rendering water potable requires?
removal of insoluble matter by settling and filtration
destruction of pathogenic organisms by chlorination
List primarily semi polar solvents
alcohol
isopropyl alcohol
glycerin
propylene glycol
polyethylene glycol 400
What is the most common solvent?
alcohol
explain why alcohol is used
by mixing with water it creates a hydro alcoholic solution both alcohol and water soluble compounds
Advantages of Semi Polar solvents
better solubility for many compounds
can be used as co solvent
better stability
How can semi polar solvents have better drug stability
decreases hydrolysis
bacterial growth
Limits for Alcohol in OTC products
Children < 6 = < 0.5%
Children 6-12 = <5%
Adults = <10%
List miscible with a wide range of solvents
caster oil
water
alcohol
List the types of alcohols
denatured alcohol
absolute alcohol
diluted alcohol NF
rubbing alcohol
Define denatured alcohol
has additives to render it more poisonous and unfit for internal uses
Define absolute alcohol (100%)
dehydrated alcohol UPS
water free ethanol
Define diluted alcohol NF
prepared by diluting Alcohol USP with an equal volume of purified water
useful as hydro alcoholic solvent in pharm preps
Define rubbing alcohol
around 70% by volume
effective antiseptic -disinfectant
for external use only
Define Miscible solvents
a solute may be more soluble in a mixture of solvents than in one solvents
Explain the cosolvent effect
the solubility is improved if some alcohol is added to an aqueous formulation
Explain mixed solvents
if there are two or more solvents and two or more solutes in formation
each soluble should be dissolved in the solvent in which it is most soluble before mixing with other liquids
Explain Complex formulation
complexes are loose molecular association that can either increase or decrease solubility
What points should be shared in counseling when using a complex formulation?
tell pt to avoid taking milk or dairy products containing calcium within 2 hours of taking tetracycline
What should you avoid with calcium and iron?
certain antibiotics
certain medications used to treat osteoporosis
thyroid medication
when preparing a solution, solubility is improved by
stirring
elevated temp
reduction of particle size
salt form rather than base form
sometimes: mixed solvent system
List ways that drug concentrations of a drug can be expressed
mol/L
mol/kg
g/l
w/v, w/w, v/v
ppm
Why are additives added to oral adminstration?
storage stability, enhance solubility, taste
Requirements in the preparation of oral solutions
physical stability
chemical stability
microbiological stability
Describe Physical stability and list examples
stability that can be seen or felt
no discoloration/cloudness
no precipitation
no loss of elegance
no loss of taste
Define chemical stability
there must not be changes to the molecular structure of the drug
What are some factors of chemical stability?
pH
hydrolysis and oxidation
How can you reduce these chemical instabilities?
Hydrolysis can be controlled by using non-aqueous solvents e.g. alcohol
Oxidation can be controlled by adding antioxidants e.g. ascorbic acid, sodium bisulfate
Explain microbiological stability
Enhanced by the use of solvents with “preservative” action e.g. >20% glycerin, alcohol
Explain why it need to be palatability
The product must taste good
Sweeteners e.g. sucrose, sorbitol, etc.
Flavours
Explain the need for a pleasing appearance
The product must look good “pharmaceutical elegance”.
in order to be used and sold
How could we have pleasing appearance?
often add colors or viscosity inducing agents to solutions
List characteristics of the Ideal additive
- pharmacologically inactive and non-toxic
- potent, therefore can be used in low concentrations
- no unpleasant odour or flavour
- compatible with drug and other excipients
- stable to changes in pH or exposure to light and heat etc.
- soluble in the vehicle/solvent
What are the types of flavors?
salty
bitter
sour
sweet
What is the mechanism of taste?
*A substance dissolves in the water layer on the tongue
*The solution is in contact with the taste cells and initiates a nerve impulse
*The impulse is transmitted via the cranial nerve to the brain; the perception of taste results
What must happen for the substance to be tasted?
they must be dissolved
Explain sweet
low molecular weight poly-hydroxyl compounds (e.g. sucrose, sorbitol, mannitol)
(number of OH groups ∝ sweetness)
Explain Sour
a result of H+ ions, therefore proportional to [H+]/acidity
Explain bitter
high molecular weight salts, free
bases and nitrogen containing compounds like amides (e.g. caffeine, codeine)
Which flavour is the most objectionable and most common?
Bitter
Explain Salty
low molecular weight salts and ionic compounds (anion + cation)
(e.g. NaCl, ammonium chloride, Na salicylate)
What is one major thing to keep in account when selecting flavoring agents?
look at str of empds in your formula and can estimate what it’ll taste like
List flavoring techniques
- Physiological
- Physical
- Masking or overshadowing 4. Blending
- Chemical
Explain how physiological flavoring techniques work
anaesthetizethetastebuds/receptors
How does physical work for flavoring
prevent dissolution of drug
Examples of physiological flavoring techniques
carbonated beverages
stores produce in fridge
apply ice cubes on tongue before taking the medication
Examples of physical flavoring techniques
use of a viscous fluids
formulate an emulsion instead of a solution
coating tablet
Explain how overshadowing flavoring techniques work
Addition of a flavour whose intensity is longer and stronger than the taste of the drug
Explain how blending flavoring techniques work
add flavours which compliment the taste and modify the flavour perception
List examples of blending flavoring technique
sour taste - blended with fruit flavours
bitter taste - adding salty, sweet and sour flavour
Explain how chemical flavoring tech works
drug can be complexed or a prodrug can be made
used in drug product manufacturing
Should not affect the overall therapeutic profile of the drug Microencapsulation or nanoencapsulation also done
Give an example of chemical flavoring technique
tetracycline dispensed as HCl salt
What are 2 categories of sweeteners?
natural sweeteners
artificial sweeteners
List of 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
Examples of Sweeteners - Sugars
Sucrose
Lactose
Dextrose
Define Sucrose
disaccharide (glucose,fructose)
standard for sweetness
What are some possible concerns with sucrose?
high water solubility but may reduce the water solubility of other solutes/drug
may pose a problem for diabetic pt
has a tendency to crystallize on the threads of bottle caps
inversion & caramelization
Define Lactose
milk sugar
disaccharide –> galactose-glucose
less sweet than sucrose
Define dextrose
glucose, corn sugar
monosaccharide
less sweet than sucrose
generally not used in oral products but sometimes as IV solutions
List types of sweeteners - artificial polyols
glycerine
propylene glycol
List types of sweeteners - natural polyols
sorbitol
mannitol
xylitol
sucralose
stevia
Define Sorbitol
approximately 2.6 cal/g (4 for sucrose), more slowly absorbed
less sweet than sucrose (0.6 x sucrose)
Can cause gas/flatulence
Define Mannitol
approx, half the caloric value of sucrose
less sweet than sucrose
high intake has laxative effects
Define Xylitol
approx. equal sweetness to sucrose but absorbed more slowly, negligible affect on blood sugar metabolized irrespective of insulin
more expensive than sucrose
Define Saccharin
tends to have a bitter metallic after taste
define cyclamate
approx. 30 times sweeter than sucrose
define aspartame
non-carb nutritive sweetener
ADR - seizures, headache
Problems with Aspartame
intolerance in pt with PKU
- this is a deficiency in the enzyme phenylalanine hydroxylase
Define Sucralose
600 x sweeter than sucrose
not metabolized (non-caloric)
not bitter after taste
Define Stevia
200 x sweeter than sucrose –> some after taste
Why is flavoring needed?
most flavors are bitter and require sweetening to make them more pleasant to taste
Why use colors?
to enhance the esthetic quality of the preparation
to act as a sensory adjunct to flavor
Why do pt usually reject dark colors?
because they are often associated with poisons
Two possible instances this speculation will not work?
Not practical for a child because they have not yet developed color/aroma/taste correlation.
It is deterrent if the patient must take multiple doses, so it is best to avoid this method when possible
As a compounding pharmacist do you think it is safe to use liquid stock colorants available in grocery store as they are also FD&C approved?
No
need material safety data sheet
- impurities
- stability
-interaction
Types of Natural Coloring Agents
mineral pigments
plant pigments
animal pigments
Define mineral pigments
primarily used for lotions, cosmetics and other external preparation
define pigments
insoluble materials that give colors when dispersed in some liquid
List some examples of mineral pigments
yellow ferric oxide
white titanium dioxide
red (red ferric oxide and carbon black)
List some examples of plant pigments
green chlorophyll
orange B carotene
yellow saffron
List synthetic color certifications
FD&C
D&C
external D&C
Explain what FD&C
food, drug and cosmetic
Explain what D&C
drug and cosmetic
Explain D&C
not allowed in products for lips
Problems with Synthetic Color Agents
carcinogenicity probability
hypersensitivity
hyperactivity
When are preservatives CI?
neonates
ophthalics
parenteral greater than 30 ml
Alternative strategies when preservatives are needed but contraindicated:
Prepare single doses
Prepare a limited quantity that will be used within a short time period
store under refrigeration and label with a short beyond use date
Requirements for preservations
activity needs to be broad spectrum
must reduce a microbial population significantly and prevent subsequent re-growth
synergistic combinations like benzalkonium pathogens like P aeruginosa
Define Antioxidants
divert the oxidative process
How do antioxidants work?
by reacting with one or more compound in the formulation to prevent free radical medicated chain reaction
Antioxidants for aqueous systems
for ascorbic acid
Na sulfite
bisulfite
Antioxidants for oil systems
BHA
alpha-tocopherol
Define buffers
control the ph of solution and therefore the staiblity of the product
buffer solution contains a weak acid and its conjugate base so that the pH of the solution changes little when acid is added
What are viscosity Inducing agents?
used to change the consistency of a preparation to render it more resistant to flow
makes the product easier to pour for the pt
may improve appearance and palatability
For topical solutions, viscosity is essential:
for achieving desired smoothness and consistency
ease in applying
will remain in contact with affected area like in ophthalmic formulations to increase residence time
List some examples of viscosity inducing agents
methylcellulose
carboxymethylcellulose
hydroxypropyl methylcellulose
acacia
tragacanth
bentonite
What is the challenge with viscosity?
creates difficulty when trying to dissolve drugs in the vehicle
What is the solution to viscosity affecting dissolution?
do not try dissolving drug in a viscous medium
add viscosity inducer after dissolving the drug
Explain surface active agents
chemicals that contain both hydrophilic & hydrophobic regions
also called wetting agents
modulate solubility of ingredients to improve stability and sometimes bioavailability
Classifications of aqueous solutions
syrups
aromatic waters
Classifications of non-aqueous solutions
elixirs
spirits
tinctures
Define aqueous solutions
the most prevalent of the oral solution
dissolving a drug in water along with excipients makes an aqueous solution
What is always used in preparing compounded aqueous solutions?
distilled or purified water
why we should know about the compatibilities of medicinal ingredients in solvents used in commercial products?
we need to know if something looks wrong so we don’t endanger the pt
Define syrups
are concentrated, viscous, sweetened, aqueous solutions that may contain less than 10% alcohol
List some non medicinal ingredients
Citric acid, flavor, glycerin, polyethylene glycol, propylene glycol, sodium benzoate, sodium citrate, sorbitol, sucralose, water and xanthan gum.
the most common oral solutions dispensed to patients are ___ and ___?
syrup and elixir
Compared to syrups, elixirs are generally:
______ sweet
less
Compared to syrups, elixirs are generally:
______ viscous
less
Compared to syrups, elixirs are generally:
______ effective in masking bitterness
less
Compared to syrups, elixirs are generally
Always contain ______ in ranges between _____%
alcohol
3-44%
Compared to syrups, elixirs are generally:
______ stable physically
more
Compared to syrups, elixirs are generally:
______ stable chemically
more
Simple syrup contains ____ w/v or ____ w/w sucrose in water
85%
65%
Common form of tincture seen in pharmacy is _____ which is used as an _____
iodine tincture
antiseptic
0.5 grams dissolved in 100 ml of solution –> best way to represent its concentration is ______
percentage
What level of sugar does the syrup have to be in order to need antimicrobial preservative?
<80%
Purpose of colorant
may be added to a syrup to enhance the appeal of the syrup
mostly it is correlated with the flavor
Define cherry syrup
a sucrose based syrup containing 47% by volume cherry juice
What is the case when the coloring does not match the flavor?
raspberry flavor but colorless solution
What is cocoa syrup flavored with?
vanilla to help with the bitter taste
What need to be determined before using a flavoured syrup?
if acidic, neutral or slightly basic and whether this will cause a problem with stability of the added medicinal agent
Why should we be aware of flavoring agents stability or ph?
solubility is dependent on pH
chemical stability of acid or base liable drugs
Define Simple Syrup
Saturated solution of sucrose in water.
85% w/v or 65% w/w
Sucrose 850g + purified water qs ad 1000ml.
Syrup is fully saturated and self-preservative
If diluted, it will support mold and other microbial growth.
What is the compounding methods for a drug within syrup-based formulations?
In formulas containing both drug and sucrose, each ingredient is usually dissolved separately and then mixed together in such a way to avoid precipitation
Define aromatic waters
are clear, saturated aqueous solutions of volatile oils or other aromatic substances
used as flavoring or perfuming solutions
What might be used to make aromatic waters?
use of talc
What are the steps for compounding aromatic water?
volatile oil + talc + purified water
thorough agitation for 30 minutes
filtration is performed
What is the role of talc?
acts as a distribution agent
act as a filter aid
Explain how talc acts as a distribution agent
increase the surface area of the volatile substance that is exposed to water and to facilitate the saturation of the solution with oil
Explain how talc acts as filter aid
remove excess volatile substance
What are some limiting factors on non aqueous solutions?
their irritation or toxicity profiles
List some examples of non aqueous solutions for internal use
glycerin
alcohol
propylene glycol
List some examples of non aqueous solutions for topical solutions
aliphatic hydrocarbons
ether
glyceryl esters of aliphatic acids
Common non aqueous solutions are
elixirs
spiritis
tinctures
Define elixirs
clear, sweetened hydro alcoholic solution intended for oral use
What is the range for elixirs
3 to 44%
most 5 to 10 %
What level for elixirs does it require antimicrobial preservative?
10-12%
Compared to syrups, elixirs are
______ able to maintain water and alcohol soluble components in solution
more
Compared to syrups, elixirs are
______ long term stability
more
Compared to syrups, elixirs are
______ strict storage conditions due to alcohol
more
Define compounding elixirs
Alcohol soluble constituents are dissolved in the alcohol portion and water-soluble constituents are dissolved in the water portion simple solution by agitation
Why is aqueous solution added to alcohol solution with constant stirring?
Order is important to maintain the highest possible alcoholic strength* at all time so that minimal separation of the alcohol soluble components occur
What to do if elixir shows precipitation?
Glycerin, sorbitol or propylene glycol aids in dissolution
Permit to stand for few hours provide time to ensure saturation and then remove the insoluble material by filtration.
Define spirits
alcoholic or hydro alcoholic solutions of volatile substances
What alcohol range is need for spirits?
62-85%
what are most spirits used for
flavouring agents in small quantities
stock solution as a convenient means of obtaining a proper amount of flavoring oil
Define tinctures
Are alcoholic or hydro alcoholic solutions of non-volatile substances prepared from vegetable or chemical substances.
What is the alcohol concentration for tinctures?
15-80%
Why should it be stopped and not exposed to high temperatures?
high alcohol content - explosive or evaporation
What is tinctures of potent drugs have?
10 g of drug per 100 ml
What is non potent tinctures?
20 g of drug per 100 ml
Why do we not use many tinctures?
not prescribed anymore usually due to high alcoholic
Do tincture need preservatives?
no because Alcoholic content of these preparations protects against microbial growth and keeps the alcohol-soluble material in solution
What cannot be mixed with tinctures?
successfully with liquids too diverse in solvent character without inducing precipitation of the solute.
what is one storage requirement for tinctures?
Must be stored in light resistant containers and protected from sunlight. Most contents of vegetable oils are light sensitive
List some examples of tinctures
Oral – may have unpleasant or burning taste due to alcohol content
Oral – example: opium tincture (17-21% ethanol)
Topical – examples: iodine (first aid antiseptic), thimerosol (antiseptic) – these are about 50% ethanol
Flavouring agents – vanilla tincture, sweet orange peel tincture
Glycerin may be included to increase solubility and stability of the active agents in the tincture
List some other pharmaceutical liquids
Gargles, mouthwashes
Otic solutions
Ophtalmic solutions
Nasal solutions – nasal wash or medicated
Lotions
Liniments
Enemas
Parenteral injectables (SQ, IV, IM)
Why are dryg mixtures for reconsitiuted solutions?
to extend the shelf life
this drug mixture may then be reconstituted as a solution
have 7 - 14 days