What is the most frequently prescribed dosage form?
tablets
What makes tablets so desirable?
stable
elegant
effective
What determines the size and format of a tablet?
the die and punch used
the amount of fill
the amount of pressure applied to the fill
Why are tablets convenient?
easy to handle
easy to identify
east to administer
Why would you make a multiple compressed tablet instead of a compressed tablet?
if you need to separate incompatible drugs/ingredients
for modified release (can administer 2 doses at once b/c the outside is the first dose and the inside will come later)
What are the 2 types of multiple compressed tablets?
1. multiple-layered tabs: multiple feed and multiple compression of fill within a single die
2. tablet within a tablet: core tablet placed precisely within the die for compression with surrounding fill
What are the different types of tablets?
1. sugar-coated
2. film-coated
3. gelatin-coated
4. enteric-coated (delayed release)
5. buccal
6. sublingual
7. chewable
8. lozenge/troche/drop/pastille
9. lollipops
10. effervescent
11. molded
12. tablet triturates
13. vaginal
14. extended release
15. rapid dissolving tablets (RDT)
What is PVP and what does it do?
polyvinylpyrrolidone
binding agent
What is another name for a sugar coated tab?
"dragee"
What is a sugar coated tab?
several layers of colored or uncolored sugar solution
-sugar solution made out of:
-acacia or PVP
-sucrose
-gelatin
What are steps taken to make a sugar coated tab?
coating
polishing
tumbling
What are the disadvantages of sugar coated tabs?
a lot of time required
a lot of expertise required (difficult to make sugar even over whole tab)
you get a lot of sugar in one day if you are taking multiple doses
the final tab can increase in size and weight up to 50%
have to have special imprinting on every tab per FDA
What is used to polish sugar coated tabs?
a cloth or canvas impregnated with carnaubu wax/beeswax
or a spray with wax dissolved in acetone
What is used to tumble sugar coated tabs?
talc for high luster
What is an advantage of sugar coated tabs?
they cover up bad taste and smell
What kind of tabs are 99% of those in the U.S.?
film-coated
T/F: Tablets made for clinical trials do not and should not have marking on them.
True
What are some advantages of film-coated tabs vs. sugar coated?
they are less time consuming to make
they are less bulky
they are durable
they are colored
they are protected
they can be made with multiple layers of coating for different times of release (15min, 30min, 1 hour all in one tab)
What is a film coated tab?
a thin layer of aqueous or non-aqueous polymer solution like plastic
-cellulose acetate phthalate
-cellulose ether polymers
What is an advantage of phthalates?
they are cheap and easy to make (colored, printed)
What are gelatin-coated tabs (caplets)?
capsule-shaped compressed tablet coated with gelatin
What is better about gelatin coated tabs?
they could taste better and look better
might go down easier
faster acting than film coated
What are the characteristics of polymers, cellulose, and gelatins?
Polymers: make plastics, there are different forms
Cellulose: we cannot digest it, excreted through the feces
Gelatin: will be absorbed and can be nutritive form of protein
What are enteric coated tablets?
NOT the same as extended release!
have DELAYed release properties
made for the intestines, not the stomach
Why would we use enteric coated (delayed release) tablets?
1. protect the drug
2. protect patient gastric mucosa
3. enhance absorption of drug
What materials are used to make enteric coated tabs?
shellac (#1 ingredient because it won't dissolve in the stomach)
phthalate derivatives
What two factors do we base the formation of enteric coated on?
1. the transit time required for the passage of the tab from the stomach to the intestine
2. the pH of the environment
What are buccal tabs?
placed in the cheek pouch
dissolve slowly
absorbed through the oral mucosa
What are sublingual tabs?
placed under the tongue
prompt dissolution
absorption throughout the oral mucosa
need to be under the tongue for at least 10 minutes
What are chewable tabs?
chewed/dissolved in the mouth
made with a creamy base like mannitol, xylitol, sorbitol
xylitol is sugar-free
flavored and colored
good for kids and adults who have trouble swallowing
NEED to be chewed, not sucked on!
What is it about mannitol, sorbitol and xylitol that makes them have a good sensation in the mouth?
their negative heat of solution leaves a cool mouth feeling upon dissolution
What are lozenges? And what are the 3 other names for a lozenge?
AKA troche, drop, or pastille
a hard, candy-like substance or gummy-like substance
can be gelatin based
can be sugar or sugar-free
dissolve or disintegrate slowly in mouth
highly compressed
active drug should be heat stable
made for local effects (if chewed you are defeating the true purpose so DON'T chew!)
What are lollipops?
sugar-based lozenge on a stick (can be sugar-free)
can make out of any drug or base
less chance of patient trying to chew lollipop vs. a lozenge
ex: Fentanyl Actiq relieves chronic cancer pain
What is an effervescent tablet?
a compression of effervescent salts that release CO2 when dissolved in water
DO NOT swallow whole!
What are molded tablets?
hard to make uniform
hand-operated tablet press used to mold and soft-compact
What are tablet triturates?
"old fashioned" tabs containing small amounts of potent drugs
prepared with minimal compression to allow ease of crushing for compounding or rapid dissolution.
not used anymore
What are 3 problems of rapid dissolving tabs?
1. friability
2. taste is hard to mask because dissolve so fast
3. drug loading
What is friability?
how easily a tablet crumbles
How should RDTs be packaged?
wrapped individually to avoid coming in contact with each other and crumbling
What are RDTs?
super-disintegrants
contain very water-soluble exicipients
Who should take RDTs?
children and elderly
What are the two types of technologies for creating RDTs?
1. lyophillization (foaming of ingredients and pouring into a mold)--> Zydis tabs
2. compression of super disintegrants with small amount of effervescent material)--> DuraSolv, OraSolv, FlashTab, WowTab
T/F: Vaginal tablets (inserts) can be termed suppositories.
False
What are vaginal tablets?
uncoated because the enzymes in the vagina are not like those in the GI to break down coatings
bullet-shaped or ovoid
only for local effects
aka ovules or inserts
What are extended release tablets?
they release medication in a pre-determined manner over an extended period of time
"dumping"
must be tested "in vivo" and "in vitro"
What are the 2 disadvantages of a rotary tablet machine?
1. lamination
2. capping
What is the max amount of loss to crumbling allowed by USP?
1%
What is the max amount of error allowed for the amount of active ingredient in a group of 10 tablets?
10%
should be between 90-110%
When making tabs by wet granulation, what ingredients are used to make the liquid binder/adhesive mixture?
a 10-20% aqueous/alcoholic solution of cornstarch and PVP
25-50% soution of glucose, molasses, gums like acacia, cellulose derivatives, gelatin
When making tabs by wet granulation, which mesh size do you pass through first?
big (6-8 size) to obtain granules or pellets
When making tabs by wet granulation, which mesh size do you pass through last (during drying)?
small (12-20) to make granules smaller and uniform in size
Why do you need to dry the damp mass of granules during wet granulation of tabs?
to evaporate teh alcohol and PVP
What do you do with granules after drying them in wet granulation method?
blending- you add the granules to a dry lubricant such as talc, stearic acid, Mg Stearate, Ca Stearate, or Zn Stearate
What do you do after blending in the wet granulation method?
compression using either a single punch tablet press or a rotary tablet machine with multiple punches.
What is the all-in-one granulation method?
uses sophisticated machinery
the granulation is prepared by a microwave vacuum process or fluid-bed process
When would you use dry over wet granulation to make tablets?
if the drug itself has its own binding properties
if your drug is degraded by high heat or moisture
What are the binding ingredients used in dry granulation of tabs and how much?
6-12% methylcellulose or hydroxymethylcellulose
How are powders compressed during dry granulation?
using a slugging machine or a roller compactor
When would you use direct compression for tablets?
When the excipients have free-flowing and cohesive properties
What are some examples of direct compression drugs?
Methenamine
Potassium Chloride
Dibasic Calcium Phosphate
Why do we coat tablets?
1. to protect drug from air
2. to protect drug from humidity
3. to protect gastric mucosa from irritating drugs
4. to mask taste of drug
5. for special release (enteric coating)
6. to provide color, symbol, aesthetics
What are the 3 types of coating for a tablet?
1. sugar
2. enteric
3. film
What is a friabilator?
a device that measures the tendency of a tablet to crumble while in a tumbling container
helps determine how much powder is lost during transit
What 4 factors determine the thickness of a tablet?
1. pressure applied
2. amount of fill
3. diameter of the die
4. compaction characteristic of the fill
T/F: In vitro dissolution tests are mandatory for approval of marketing by FDA and other reg. agencies of other countries.
TRue
What is the purpose of a dessicant packet in a bottle of tablets?
to reduce humidity
What is the purpose of cotton/cotton balls in a bottle of tablets?
to maintain tight packaging and reduce crumbling
What is the difference between topical dermatological products and transdermal products?
topical dermatological= deliver drug into the skin to treat dermal disorders (topical absorption)
transdermal products= deliver drugs through the skin to the circulation for systemic effects (skin is not the target)
T/F: topical preps can be administered to the eye.
True
T/F: Transdermal topical products go through all layers of the skin, including the epidermis and dermis.
True
What are the 5 factors that affect drug penetration of topical preps?
1. occlusive dressings
2. surface area
3. condition of the skin
4. base used
5. pressure/rubbing
What are ointments?
semisolid preps for external application to the skin or mucous membranes
can be medicated or non-medicated
applied to dry, scaly lesions on the skin, mucosa and eyes
What are 3 characteristics of a good ointment?
1. soften or melt at body temperature
2. spread easily
3. are not gritty
What does the word "unguent" refer to?
ointments
What ingredients can be found in an ointment?
-active drug
-humectants
-preservatives
-stiffeners
-antioxidants
-ointment base
-penetration enhancers
What are humectants used for?
to prevent loss/escape of moisture
What are antioxidants used for (in ointments)?
to prevent rancidification
What is a common penetration enhancer for ointments?
urea
What are two examples of an oleaginous ointment base?
white petrolatum
white ointment
What are 4 examples of an absorption ointment base?
hydrophillic petrolatum
anhydrous lanolin
aquabase
aquaphor
What are 5 examples of W/O emulsion ointment bases?
nivea
eucerin
hydrocream
hydrous lanolin
cold cream
What are 4 examples of O/W emulsion ointment bases?
hydrophillic ointment
dermabase
velvachol
unibase
What is an example of a water soluble ointment base?
PEG ointment
Which ointment base has these characteristics?
-greasy
-occlusive
-emollient
-will not absorb water
-not water washable
-insoluble in water
Oleaginous
Which ointment base has these characteristics?
-insoluble in water
-not water washable
-anhydrous
-can absorb water
-emollient
-occlusive
-greasy
absorption base
Which ointment base has these characteristics?
-insoluble in water
-greasy
-occlusive
-emollient
-contains water
-will absorb water
-not water washable
W/O emulsion base
Which ointment base has these characteristics?
-insoluble in water
-water washable
-will absorb water
-contains water
-nonocclusive
-nongreasy
O/W emulsion base
Which ointment base has these characteristics?
-nongreasy
-nonocclusive
-anhydrous or hydrous
-will absorb water
-water washable
-water soluble
water soluble base
What do emulsifiers do?
they allow water and oil to be mixed together by creating droplets of either the water or the oil
How far does an epidermic base penetrate and what is an example?
it penetrates none or very little
oleaginous
How far does an endodermic base penetrate and what is an example?
it penetrates into the dermis
absorption
How far does a diadermic base penetrate and what is an example?
it penetrates into and through the skin (most penetration)
emulsion
water soluble
What are the 3 ways to manually prepare an ointment?
1. ointment tile + spatula
2. mortar and pestle (for more liquid preps like calamine lotion)
3. ziploc bag
What is the mechanical mortar and pestle called?
the unguator
What do we call the 2 general methods for compounding ointments?
fusion
incorporation
T/F: It is easier to mix oil and water with a large quantity mixer than by hand.
True
What do astringents do?
they close off top layer of skin cells and "create" a new layer (Glaucia's words)
What factors influence the selection of an appropriate ointment base?
rate of drug release
enhancement of percutaneous absorption
occlusion of moisture
stability of drug in presence of water
influence of drug on other components of the formulation
T/F: A lipid soluble drug should go into a water soluble base.
True
T/F: A highly lipid soluble drug should go into a lipid base because it will dissociate when it touches the skin.
False; should not go into a lipid base!
What is the main goal of incorporation?
to achieve uniformity
How much levigating material should be used to improve wetting?
4-6%
a minimal amount
If too much glycerin is added to a prep, what will be the result?
reduced shelf life and
reduced suspendability
T/F: You should not melt your ointment base to add your solid drug to it.
False, you can melt it
_____are used for more localized areas, while ________ are used for spreading across large areas of the skin.
ointments/////lotions
T/F: We can dissolve solids in a small amount of solvent that is compatible with the base if we want something a little more liquid.
True
It is most important for the levigating agent to be miscible with: the drug itself or the base?
the base
Which levigating agent can have a laxative effect?
mineral oil
Which levigating agent is good for mixing with greasy bases?
mineral oil
Which levigating agents are good for mixing with water-containing bases?
glycerin
propylene glycol
PEG 400
Tween 80
Which levigating agents are not good for mixing with water-containing bases?
cottonseed oil
mineral oil
castor oil
Which levigating agent is pretty much miscible with water or any other oil or levigating agents?
Tween 80
What is coalescence?
breaking of the emulsion (oil and water phases separate)
don't want this!
What is the max capacity for an absorption base to accept liquids?
40-50%
T/F: Alcohol will destroy an emulsion if too much is added.
True
Why are absorption bases more versatile?
because they can accept water or grease
T/F: with an emulsion base, you want to mix the drug with a levigating agent that is miscible with the external phase?
true
T/F: It would be possible to add 25 mL of liquid to 50g of an ointment?
True
T/F: Scents are essential oils so they can be added to oleaginous bases.
True
What is fusion?
melting of ingredients together and cooling with constant stirring until congealed
How do we prepare an emulsion ointment?
Heat oils and waxes together
Heat water and water soluble ingredients separately
Slowly add water (aqueous phase) to oil phase with continous stirring
Cool with frequent stirring until congealed
Are ointments required to be sterile?
No, but ophthalmic ointments are
What types of ointments need to be additionally tested for molds and yeasts?
urethral
vaginal
rectal
what is the size range for ointment jars?
0.5 oz---1 lb.
what is the size range for tubes of ointment?
5, 15, 30g
T/F: Different bases work better in different areas of the body.
True
What temperature should ointments be kept at?
below 30 C (about room temp)
T/F: Tubes have greater protection against external contamination and environmental conditions than jars.
True
Which type of bases are relatively more stable (unless left in extreme heat)?
oleaginous
anhydrous
Which type of base is less stable?
emulsion
What is the BUD for extemporaneous non-aqueous liquids or anhydrous preps that use NF products?
25% of time remaining on product exp. or 6 months, whichever comes first
What is the BUD for preps containing water?
2 weeks (14 days)
What is a cream?
a very thick liquid for external application or an opaque soft solid
easier to spread and remove than ointments
for topical, rectal, vaginal
drug is dissolved or suspended in W/O, O/W, or other water-washable bases
Why do we apply creams?
to dry out weeping or oozing lesions
the water from the lesion mixes with the water phase in the cream and is evaporated off the skin
What are pastes?
thick, stiff ointments that don't flow at body temp. and have reduced absorption capabilities
coat the affected area to protect
contain at least 25% of solid materials that are undissolved in the base
How can we prepare pastes?
incorporation
fusion if need to increase workability of base
can use base as a levigator
T/F: A gel is a solution.
False; a dispersion
Gels are excellent drug delivery systems for what areas of the body?
oral
topical
nasal
vaginal
rectal
T/F: Gels are relatively easy to prepare, are efficacious and are compatible with many different drugs.
True
What is imbibition?
the taking up of liquid with no measurable increase in volume
what is swelling?
taking up of liquid with an increase in volume
What is syneresis?
the intense interaction between particles of the dispersed phase so that, on standing, the dispersion medium is squeezed out in droplets and the gel shrinks = instability
What is xerogel?
the removal of the liquid from a gel, leaving only the framework
-gelatin sheets
-acacia tears
-tragacanth ribbons
What is thixotropy?
semisolid gel on standing, but when shaken becomes a liquid
no change in temp or volume required to make this happen
What is the common concentration of gelling agents in a gel?
0.5-2%
must be less than 10% of prep
what are some characteristics of gels?
-water washable
-water soluble
-clear or turbid
-greaseless
-water absorbing
-can be oleaginous or alcoholic components
-disperse light
What preservatives should be used for gels/magmas?
-sodium benzoate
-benzalkonium chloride
-methylparaben
-propylparaben
What are single-phase gel systems?
gels that contain linear or branched polymer macromolecules that dissolve in water and have no apparent boundary with the dispersing medium
What are some examples of single-phase gel systems?
single phase gels made from synthetic or natural macromolecules
What are two phase gel systems?
gels that contain small, discrete particles
are thixotropic
What are some examples of two-phase gel systems?
-aluminum hydroxide gel
-bentonite magma, NF
What makes a gel a magma?
must be two-phase system with LARGE particles suspended or floccules of small, distinct particles
What are some common gelling agents?
-acacia
-pectin
-starch
-tragacanth
-xantham gum
-alginic acid (seaweed)
-animal/vegetable fat (lard, cocoa butter)
-gelatin
-bentonite, veegum
-CMC
-Pluronic F-127
-other methylcelluloses
-carbomer resins
-PEGs
-colloidal silicon dioxide
-Polyvinyl alcohol (PVA)
-petrolatum
-mineral oil
-polyethylene gel
-plastibase
T/F: the continuous phase of most gels is usually aqueous but can also be alcoholic or oleaginous.
True
What do neutralizers do for a gel?
they thicken the gel after the gelling agent has been dispersed
What are some examples of neutralizers?
-Sodium hydroxide or Potassium hydroxide if alcohol content is less than 20%
-Triethanolamine is alcohol is greater than 50%
-sodium carbonate
-ammonia
-borax
What are plasters?
adhesive masses spread onto the backing of paper, fabric, moleskin or plastic
provide prolonged contact and effect at the site of application on the skin
sized to fit area
What are glycerogelatins?
plastic masses containing 15% gelatin, 4% glycerin, and 35% water, and 10% active drug
similar to gummy base prep
warmed and melted prior to application
What is an example of a glycerogelatin?
zinc gelatin for varicose ulcers
T/F: External wounds should be open to the atmosphere/air whenever possible.
True; unless there is an infection or prescribed to cover
T/F: A pharmacist can substitute one cream, ointment, or paste for another.
False; not without doctor's consent
what does supponere mean?
to place "under" the body
What are some advantages of suppositories?
-avoid irritating the stomach
-avoid gastric pH/enzymes
-bypass the liver (partially avoid first pass effect
-can be used for patients unable or unwilling to swallow
-fast acting
-can be used if patient is vomiting
What are factors that affect the absorption of a suppository?
-lipid-water solubility
-particle size of drug
-base selection
-colonic content
-circulation route
-pH and buffering capacity
What symptoms of the rectum might affect absorption of a suppository?
-dehydration
-diarrhea
-rectal tumors
T/F: Rectal fluids are relatively neutral in pH.
True
What are the 3 main types of suppositories and what are some other types of dosage forms for those areas?
1. rectal
2. vaginal
3. urethral
-vaginal tablets
-intrauterine contraceptive sponges
-intrauterine drug delivery systems
-powders
-solutions
-jellies
-gels
-ointments, creams
-aerosol foams
What is the local effect of rectal suppositories?
relief of hemorrhoids
relief of constipation
what are some systemic effects of rectal suppositories?
antiemetic
tranquilizers
anti-inflammatories
asthma
About how long and how much does an adult rectal suppository measure?
4cm
2grams
How much does a child rectal supp weigh and how long is it?
1 gram
2cm
What type of suppositories are used as a cathartic?
glycerin supps
What should a patient first do with PEG or glycerinated gelatin supps before inserting?
moisten with warm water to aid with lubrication and dissolution
T/F: Suppositories can be frozen.
False; never
A PEG suppository with how much water should be dipped in water to prevent dehydration of rectal mucosa and stimulate peristalsis?
less than 20% water
What does "pessaire" mean in French?
tampon
What is the typical weight of a vaginal suppository?
up to 5 grams, but it can vary
What are the preferred bases to be used for vaginal suppositories?
PEG
glycerinated gelatin
Are there any systemic uses for a vaginal suppository?
Usually no, but can be progesterone for PMS
What are some local effects of vaginal suppositories?
combat infections of genitourinary area
restore vaginal mucosa to a normal state
contraception
What are some infections that can occur in the vagina and are treated with vaginal suppositories?
Trichomonas vaginalis
Candida albicans
Haemophilus vaginalis
How do we treat Trichomonas vaginalis?
with a povidone-iodine suppository
How do we treat Candida albicans?
with nystatin, miconazole, clotrimazole, or terconazole suppository
How do we treat Haemophilus vaginalis?
sulfathiazole or sulfacetamide suppository
How do we restore the vaginal mucosa to a normal state?
with an estrogenic substance suppository
What drug can be used to prepare a contraceptive vaginal suppository?
Nonoxynol-9
Octoxynol
What does "bougie" mean in French?
candle, in reference to a urethral suppository
What is the length of a typical female urethral suppository?
50 mm and 3-6mm in diameter
What is the length of a typical male urethral suppository?
140mm and 3-6 mm diameter
What is the main goal of inserting a urethral suppository?
to be an antibacterial
to be an anesthetic
What is Muse?
a male urethral suppository used to treat erectile dysfunction
Alprostadil
What are some characteristics of good suppository bases?
stable
non-irritating
chemically and physiologically inert
compatible with many drugs
stable during storage
esthetically acceptable
should melt or dissolve in body fluids
should allow drug to be released
have high melting points if using a drug like camphor, menthol, or phenol
What are the 4 main types of suppository bases?
1.fatty, oleaginous, or oil soluble bases
2. hydrogenated vegetable oils (emulsions)
3. water-soluble and water-miscible bases
4. miscellaneous bases
What is the most frequently used suppository base?
cocoa butter/theobroma oil
What is another name for cocoa butter?
theobroma oil
At what temperature does a cocoa butter supp melt?
34 C
Why should cocoa butter be melted slowly in a water bath?
because if heated to quickly at high heat and then quickly cooling will lead to a metastable crystalline form with much lower melting point
supp will melt before you can even put it in
When should you add an emulsifier to your cocoa butter suppository?
when you are using water soluble drugs
Which type of drug should you not mix with cocoa butter to make a suppository?
fat-soluble drugs because they will not absorb in the body
What is an example of a fatty, oleaginous, oil soluble base for suppositories?
Cocoa butter
What are 2 examples of a hydrogenated vegetable oil (emulsion) base for suppositories?
fattibase
wecobee
What is fattibase/wecobee?
supp base made from triglycerides from palm, palm kernel, and coconut oils
emulsifiers and suspending agents added
have a slightly higher melting point than cocoa butter
What are 3 examples of water-soluble/water miscible suppository bases?
PEGs
Polybase
glycerinated gelatin
What are water-soluble/water miscible supp bases?
when mixed with drug, they allow teh drug to dissolve and mix with aqueous body fluids
can cause local irritation because they can dehydrate the rectal mucosa
What is the most popular water-soluble suppository base?
PEG
How are PEG bases made?
with polymers of ethylene oxide + water
T/F: PEG bases dissolve slowly in body fluids and do not melt.
True
Why do PEG suppositories need to be dispensed in glass or cardboard containers?
because the PEG interacts with polystyrene
What is the molecular weight of a solid, wax-like PEG?
greater than 1000
What is the molecular weight of a liquid PEG?
less than 1000
T/F: You can mix a low molecular weight PEG with a high molecular weight PEG by fusion to obtain a base with a specific consistency.
True
If you want a drug to be released slowly and you are using a PEG base suppository, should you use a high or a low melting point drug?
higher melting point
What is polybase?
a water soluble supp base
preblended homogenous mixture of Tween 80 and PEGs
does not require mold to be lubricated
stable at room temp
can be mixed with water
What is glycerinated gelatin?
a water soluble supp base
absorbs water
causes evacuation
glycerin will pull water from atmosphere, so need to be stored in a tight container
made of 70% glycerin, 20% gelatin, 10% water, and drug= RECTAL
made of 60% gelatin and 20% glycerin=VAGINAL/URETHRAL
Why is a glycerinated gelatin base not recommended for systemic rectal suppositories?
because of osmotic effect
because of defecation reflex
T/F: Glycerinated gelatin vaginal and urethral suppositories are easier to insert than ones made with cocoa butter?
True
What are some miscellaneous supp bases?
glyceryl monopalmitate
glyceryl monostearate
polyoxyl 40 stearate
What are the 2 types of miscellaneous supp bases?
1. mix of glycerin + high molecular weight fatty acids
-fatty acids are: palmitic or stearic acid
2. mix of fatty bases with water-soluble emulsions (w/o emulsions)
-stearates and glycols
What are the 3 methods used to make suppositories?
hand molding
fusion
compression
T/F: Hand molding of a suppository uses heat.
False
Which base is usually used to do hand molding of a suppository?
cocoa butter
What method of suppository making would be used if your substances are insoluble in the suppository base or the medicinal agents are heat sensitive?
compression
What substances can be used as a mold lubricant if you are making a supp with a water-soluble base?
light mineral oil
vegetable oil
What substances can be used as a mold lubricant if you are making a supp with an oleaginous base?
glycerin
propylene glycol
T/F: Lubricants are usually not needed for supp molds if they are heated and prepared properly.
True
Who should make simple syrup?
Nobody is silly enough to make simple syrup!
-Glaucia
What is a syrup?
an aqueous, sweetened, flavored, viscous solution
If a solution has a lot of alcohol in it, what is it then called?
an elixir
What are the two different types of syrups?
medicated
non-medicated (flavored vehicles)
What are the 3 types of non-medicated syrups?
1. Syrup, NF (simple syrup): 85% sucrose in water
2. Sucrose based:
-cherry syrup (acidic medium)
-chocolate syrup (bitter tasting drugs)
-orange syrup (source of tartness, acidic medium)
-raspberry syrup (disguise of sour or salty taste)
3. Commercial: both acidic and alcohol free
-Ora-sweet
-Ora-sweet SF
What are some examples of medicated syrups?
antitussives
antiemetics
antihistamines
antivirals
What are some components of syrups?
water-soluble drug
solvents: purified water, alcohol in [low]
sweetening agents
flavoring agents
coloring agents
antifungal/antimicrobial preservatives
What are some ways to prepare a syrup?
1. with the aid of a little heat
2. agitation
3. heat and agitation
4. addition of sucrose to a medicated and/or flavored liquid
5. percolation
6. maceration
Why don't we want to heat artificial sweeteners too much?
some are destroyed by heat
will get a different flavor if heated too much
T/F: Sucrose is a disaccharide of glucose + fructose.
True
Why should you not heat sucrose syrups too much?
sucrose will be inverted to a mixture of monosaccharides, glucose and fructose
becomes less sweet
color turns darker
more prone to microbial attack
What is an example of a syrup that is made by percolation?
Ipecac syrup
What does "macerare" in maceration mean?
to soak, like a tea bag
What is an elixir?
a clear, sweetened, flavored, hydroalcoholic solution for oral use
What are the two types of elixirs?
medicated
non-medicated: vehicles
T/F: A syrup may or may not have alcohol in it.
True
T/F: An elixir may or may not have alcohol in it.
False
What is the alcohol content of Aromatic Elixir, NF?
21-23%
When making an elixir, how do we prevent it from being cloudy? (want it to be clear)
add water phase very slowly, with continuous stirring to alcohol phase
T/F: when making an elixir the alcohol-soluble and water-soluble components need to be dissolved separately.
True
What are some solvents used in elixirs?
purified water
alcohol
glycerin
propylene glycol
sorbitol
What is the alcohol content allowed in an elixir for a child under 6 years old?
0.5%
What is the alcohol content allowed in an elixir for children 6-12 years old?
5%
What is the alcohol content allowed in an elixir for adults?
10-15%
How much alcohol in an elixir is considered self-preserving? (no extra preservative needed)
10-15%
What are 2 methods used to prepare elixirs?
1. simple solution with agitation
2. mix alcoholic solution with aqueous solution
Why do we add the aqueous phase to the alcohol phase when making an elixir?
because whatever is soluble in water will also be soluble in alcohol so you ensure full dissolution of solids
How should elixirs be stored?
in tight containers to prevent evaporation of alcohol
in light resistant containers
protect from heat
According to USP 23, what is a solution?
a liquid prep that contains one or more chemical substances dissolved (molecularly dispersed) in a suitable solvent or mixture of mutually miscible solvents
T/F: A solution should be clear, have nothing floating on it, and not be saturated.
True
Where can solutions be used in the body?
oral
topical
vaginal (douches)
rectal (enemas)
otic (aural)
nasal
ophthalmic
irrigating
parenteral
What are some advantages of solutions?
doses are homogenous
immediate availability for absorption
dose is easily adjustable
can be used for enteral feeding
good for nursing home patients, incarcerated, psychiatric
good for patients who can't swallow caps/tabs
What are some disadvantages of solutions?
less stable than dry form of drug
potential for microbial contamination
package is bulky and weighs more
can have dosage measurement errors
need a solvent that will allow solubility
need taste and smelling additives
What are some solutions that are classified by an aqueous type of solvent?
oral solutions
syrups
aromatic waters
What are some solutions that are classified by a NON-aqueous type of solvent?
elixirs
tinctures
spirits
fluid-extracts
collodion
liniment
oleaginous solutions
How can we increase the solubility of a solution?
-heat (but may cause precipitation in some drugs)
-use a cosolvent (glycerin or propylene glycol, alcohol, benzyl alcohol
-add salts of an organic compound
-add inorganic compound (has high water solubility)
What do Diazepam, Taxol and Digoxin solutions all have in common?
they all have limited water-solubility so they require cosolvents like benzyl alcohol, propylene glycol, or alcohol so that they will go through a needle for delivery = SYRINGEABILITY
The solubility of an organic compound depends on ______?
the pH of the solvent
T/F: Weak acids like to dissolve in weak bases.
True
T/F: Miscibility of liquids is easily predicted.
False
Can you mix castor oil and mineral oil?
no
Can you mix cottonseed oil and mineral oil?
yes
Can you mix water and alcohol?
yes
Can you mix glycerin and water?
yes
Can you mix glycerin and alcohol?
yes
Can you mix alcohol and mineral oil?
no
Can you mix alcohol and castor oil?
yes (but 50/50 only)
T/F: Injectables for human use can have colorants.
False; only for veterinary inj.
What is the #1 solvent used for liquid preps?
purified water
What is a pyrogen?
causes fever and chills
comes from products of bacteria like lipopolysaccharides
Is Water for Injection, USP, sterile?
usually but not necessarily
Tell me about SWFI.
It is sterile
It is pyrogen free
It comes in manufactured vials
It should not be injected into anybody!
It does not need to be sterilized afterward
T/F: Anything that is prepared with water for injection, USP, needs to be terminally sterilized after it is mixed.
True
Tell me about Bacteriostatic Water for Injection, USP (BWFI).
It is sterile water with an antimicrobial preservative
Cannot be used in preps for newborns or elderly because of the preservative is harsh on the liver
Will have a longer shelf life than SWFI
What is the strength of Acohol, USP? aka ethyl alcohol or ethanol
94.9-96%
What is the strength of Dehydrated alcohol, USP?
99.5% (nearly 200 proof)
What is the strength of Diluted Alcohol, NF?
49% ethanol
What is the strength of Rubbing alcohol?
70% ethanol + denaturants
What is the strength of Isopropyl Rubbing Alcohol?
70% isopropanol
What are 2 oils that can be used as solvents due to their less irritating fatty acids?
canola oil
safflower oil
What are the 3 methods by which purified water can be prepared?
reverse osmosis
distillation
ionic change
What are glycogenetic sweeteners?
they are nutritive
can be converted to energy in the body
What are some glycogenetic sugars?
sucrose (sugar, agave nectar, fruit)
dextrose (D-glucose, not L-glucose)
fructose (levulose from fruits)
What are some glycogenetic non-sugars?
sorbitol
glycerin
mannitol
xylitol
propylene glycol
**all are polyols/sugar alcohols
Why do we add sweeteners to solutions?
to mask flavor of drug and overwhelm the tasting buds
to make solutions thicker
Which gycogenetic sugar would be recommended for a patient with diabetes?
agave nectar because it transforms to glucose in the body very slowly and has a low glycemic index
What will happen if you heat D-glucose (dextrose) too much?
You will end up with L-glucose, which is salty
T/F: Glycogenetic non-sugars are less sweet, less viscous, and less antimicrobial than glycogenetic sugars.
True
Which non-sugar has 30% fewer calories than sugar?
xylitol
What is a non-glycogenetic sweetener?
has no nutritive value
is a sugar substitute
is non-caloric
What are some examples of natural non-glycogenetic sweeteners?
-Stevia
-methylcellulose
-hydroxyethyl cellulose
**all from plants
Which natural sweetener is heat stable and 30 times sweeter than sucrose?
Stevia
What are some examples of artificial non-glycogenetic sweeteners?
Saccharin
Cyclamate
Aspartame
Acesulfame Potassium
Sucralose (Splenda)
Neotame
Which artificial sweetener was banned in 1969 for carcinogenicity and teratogenicity?
cyclamate
*but still used in Coke Light in Europe
What artificial sweetener has been restricted in its use since 1977 and causes cancer in animals?
saccharin (sweet n low)
What are the 3 metabolites of Aspartame (Equal, NutraSweet)?
1. phenylalanine
2. aspartic acid
3. methanol
Why is phenylalanine bad?
it crosses the blood brain barrier and causes brain damage in people who can't metabolize this amino acid
What does heat-labile mean?
the substance can be warmed up but not baked with or it will be destroyed
What artificial sweetener has some heat stability, is unmetabolized, is 130 times sweeter than sucrose and is structurally similar to saccharin?
Acesulfame Potassium aka Sunett
What artificial sweetener is unmetabolized, heat stable, and 600 times sweeter than sucrose?
Sucralose aka Splenda
What artificial sweetener is an aspartame analog and is 30-60 times sweeter than aspartame, but with decreased amounts of phenylalanine?
Neotame
What kinds of flavors do children prefer?
sweet
fruity
berries
candy-like
What kinds of flavors do adults prefer?
less sweet
tart
sour
citrus
chocolate
What things do patients expect with respect to flavorants?
psychogenic balance with color
immediate flavor ID and development
acceptable feel in the mouth
brief aftertaste
no undesirable sensations
How many taste buds do we have?
10,000
What factors contribute to the taste of something?
smell
texture
color
temperature
flavor
T/F: Natural flavorings are more expensive than synthetic ones
True
What weight of salts are salty?
low MW (5,000 or less)
What weight of salts are bitter?
high MW salts (greater than 5,000)
What are the 3 types of flavorants?
synthetic
natural
from spices
In an organic compound, what will more -OH groups taste like?
sweeter
In an organic compound, what will esters, alcohols, and aldehydes taste like?
pleasant
will have a volatile odor
For newborns or elderly, what two components should not be added if possible?
coloring
flavoring, but flavoring usually added for elderly
Where do 90% of synthetic colorants come from?
aniline
What are some agents with inherent color?
sulfur
riboflavin
cupric sulfate
cyanocobalamine (vit B12)
Why do we use colorants?
to enhance the appeal of a dosage form
to reach a psychogenic balance with flavor
How do we select the proper colorant?
photo-stability
dye chemical stability
stability of other ingredients
shelf life
pH of prep
water or oil solubility of prep
Which colorants are allowed for external application only?
FD&C Red #2 and #4
Which colorant must be listed on labels of food and is only allowed to be used in small amounts?
FD&C yellow #5
What is the difference between a bacteriocidal and a bacteriostatic?
cidal= kills bacteria
static= stops growth or multiplying of bacteria
T/F: Simple syrup, NF, is self preserved.
True
T/F: 15% of alcohol in an acidic media is self preserved?
True
T/F: 18% of alcohol in a basic/alkaline medium is self preserved?
True
T/F: Some flavoring oils and sweeteners have antimicrobial activity.
True
What are two flavoring oils that have antimicrobial properties?
thymol
cresol
T/F: It is okay to use preservatives in a prep for a newborn.
False
_______have a broad spectrum of antimicrobial capabilities so we use them a lot.
Benzoates
T/F: Large volume parenterals contain preservatives.
False
T/F: Some ophthalmics contain preservatives and some do not.
True
T/F: Refrigeration stops microbial growth/does not allow it.
False, only slows it down
What is free water?
water in a prep that is not bound to other molecules
available for attack
What is the role of free water?
it determines the effective concentration of a preservative required for a given liquid formulation
What are the different types of preservatives?
1. alcohols and glycols
2. organic acids
3. parabens
4. mercurial derivatives
5. salts of quaternary ammonium bases
6. chlorobutanol
Which type of preservative can cause allergies in a lot of people?
mercurial derivatives
What is the most common type of preservative used in parenterals and ophthalmics?
salts of quaternary ammonium bases
What dosage forms are alcohols and glycols usually used for (as preservatives)?
oral and topical
Which preservative is approved for oral use but is not usually used because of its sharp, burning taste?
benzyl alcohol
What are the 4 major alcohol/glycerol type of preservatives?
ethyl alcohol
propylene glycol
glycerin/glycerol
benzyl alcohol
What are the 2 most common types of organic acid preservatives?
