What are some examples of small volume parenterals (SVPs)?
biologics like vaccines, toxoids, anti-toxins injections
What are some examples of LVPs (large volume parenterals)
dialysis solutions blood replenishment products IV fluids for maintenance, replacement, replenishment of fluid, electrolytes, vitamins irrigation fluids
T/F: Small volume parenterals like single dose vials are preserved.
T/F: Intravenous route is the only 100% bioavailable route of administration.
What are the 3 main advantages of an IV dosage form?
rapid, immediate action (no absorption required) optimum drug level in the blood (accuracy) can be used for uncooperative and unconcious patients
Why do fat emulsions need to be administered through a central vein and not a peripheral vein?
because their osmolarity is too high
If administering an IM injection, would you use a smaller needle or a larger needle?
If you are administering an IV medication/injection, would you use a small or large needle?
small, so you can get into the vein
What are some disadvantages of an IV route?
these dosage forms are more expensive need to be absolutely sterile in every way drug cannot be removed once it is injected (no oops) need specially trained personnel to administer
T/F: Every solution for IV administration is aqueous.
False; only exception is fat emulsions
What are the 2 major concerns/hazards associated with IV administrations?
Thrombus (blood clot formed within a blood vessel due to slowing of the circulation or an alteration of the blood vessel) Embolus (circulating clot that can lodge in a blood vessel and cause obstruction in the brain or heart)
What is a microthrombus?
a small clot that can cause elderly to faint for a short time and they will not know what happened
What is the most common parenteral route of administration?
Why do we need to rotate the site of an IM injection?
to avoid abscess, irritation, induration
What is maximum amount of fluid that should be injected IM into the gluteal area?
5 mL -will hurt!
What is the max amount of fluid that should be injected IM into the deltoid?
Where is the best place to inject an IM medication for an infant?
deltoid of upper arm mid-lateral muscles of thigh NOT gluteal in a baby, they have no butt!
T/F: IM injections are less rapid and have a greater duration than IV injections.
T/F: IM injections can be aqueous or oleaginous solutions or suspensions.
What is the preferred IM injection site for adults?
upper outer gluteal (avoid fat)
T/F: Small, short needles should be used to administer a subcutaneous injection.
T/F: irritating drugs and thick suspensions can be administered into the subQ space.
What are some examples of subQ injections?
insulin vaccines (MMR, DPT, rubella, tetanus, toxoid) growth hormone MS drugs
Where can subQ injections be given?
lower abdomen upper arm anterior surface of thigh
What is the max amount of fluid that should be injected subQ?
1.3 mL (pretty small)
T/F: SubQ injections are injected into the dermis.
false; intradermal only, subQ goes below the dermis layer
Where are subQ injections injected (in relation to the layers)?
loose interstitial tissue below the dermis
How many different parenteral ROAs are there and what are they?
4 IV (vein) IM (muscle) SubQ (below dermis) ID (dermis)
Which parenteral route is the hardest to administer?
Where should an ID injection be given?
What is the max amount of fluid that should be administered in an ID injection?
0.1mL because this area contains nerve endings and is vascularized use a very short, thin needle!
T/F: Long, thin needles should be used for an ID injection.
What are some examples of ID injections?
Diagnostic determinations for: tuberculin diptheria toxin immunizations
T/F: An injection is sterile if all living organisms are absent.
False; also non-living spores must be absent
T/F: Boiling is sufficient enough to kill all bacteria/organisms.
T/F: Oleaginous preps, oils, and exposed powders can be sterilized in an autoclave.
T/F: It is the pressure that kill organisms in an autoclave, not the temperature.
false; it is the high temp/steam
What are the 5 methods of sterilization?
steam under pressure (autoclave) filtration dry heat (sterilizing oven) ionizing radiation (gamma and cathode) gas (ethylene oxide or propylene oxide)
What method of sterilization should be used for ophthalmic ointments?
What does an autoclave do to organisms?
mix of heat + moisture denatures and coagulates some of the microbes' essential proteins
What is the standard time and temperature used to autoclave?
121 C for 15 minutes or 125 for 15 minutes for wet products
What type of products can go into an autoclave?
non-oleaginous heat stable products (thermostable)
What type of products can go in a sterilizing oven (dry heat)?
oleaginous, heat stable products products not penetrated by moisture like oils, glycerin, petrolatum, mineral oil, paraffin heat stable powders like zinc oxide
T/F: dry heat sterilizing ovens can be used for aqueous products.
True, but remember to seal them so that the liquid does not evaporate off
What is the usual time and temp setting for a sterilizing oven?
2 hour min at 160-170 C (very hot!)
Which sterilizing method is used for glassware and surgical instruments?
How does a sterilizing oven kill microbes?
the really high temp will kill them by dehydration of cells followed by slow burning or oxidative processes
What are the advantages of filtration for sterilizing?
can be done quickly no need to gown up and go into the hood filters are cheap the quality of filtration can be checked complete removal of particulate matter and microorganisms
What are the disadvantages of filtration?
filter can be defective if doing large volumes, can take a long time effectiveness of filtrate is determined by how many microbes were in it some materials can be absorbed by filter membrane
T/F: Filtration is only for very small volumes of liquid.
false; can be done with large volumes at manufacture site using + and - pressure
What type of products should be sterilized using filtration?
heat sensitive products (thermo labile) mostly small volumes
How small must a filter for filtration be in order to properly sterilize?
What are pore-sized membrane filters made of?
What does gas do to microorganisms?
it interferes with the metabolism of bacterial cells
What is the typical exposure time of a gas for sterilization?
4-16 hours (longer)
What type of products should be sterilized by gas?
heat sensitive moisture sensitive enzymes, antibiotics
T/F: gas sterilization requires specialized equipment.
T/F: gas sterilization can be done in a bag in the wilderness.
true; bag method is a kit used by travelers
Which sterilization method is widely used to sterilize medical and surgical supplies and appliances?
T/F: gases for sterilization are usually mixed with an inert gas like CO
T/F: gases used for sterilization are extremely flammable.
What are the 2 types of gas used to sterilize products?
ethylene oxide propylene oxide
T/F: Ionizing radiation is used widely to sterilize products.
False; due to fear and specialized equipment
What does ionizing radiation do to microorganisms?
destroys cells destroys/disorients chromosomal nucleoproteins of microbes rays induce microorganisms to form deleterious products
What is ionizing radiation mostly used for?
food products and in Europe
What does pyrogen-free mean?
absence of fever-producing organic substances
What are pyrogens?
lipopolysaccharides from the outer cell wall of bacteria and endotoxins cause fever in the body
T/F: pyrogens can remain after sterilizing processes like autoclaving, dry heat, and filtration.
How do we destroy pyrogens?
With extreme heat (250 C) for 30-45 minutes Also oxidizing agents like peroxides, alkali, acids, and potassium permanganate
Where does particulate matter come from?
manufacturing process packaging components (plastic) devices used for administration manipulations during prep solution itself and chemicals in it
What is particulate matter?
mobile undissolvable substances unintentionally present in parenterals
T/F: the USP allows for some amounts of particles to be in LVPs and SVPs.
T/F: parenterals often have added substances in them.
What are some added substances that you might find in a parenteral ?
buffers (to keep pH) EDTA, citric acid, tartaric acid (to prevent oxidation) benzyl alcohol, chlorbutanol, benzoates (to prevent microbes and fungus)
How can we validate there aren't any microorganisms or spores in parenterals?
biologic indicators (USP)
How do biologic indicators work?
specific spores are resistant to certain sterilization processes put them onto a carrier (strip of filter paper) or to a sample of the load to be sterilized
Which spores are most resistant to steam and are therefore used to test for sterility?
Which spores are most resistant to dry heat or gas?
Which spores are most resistant to ionizing radiation?
How can we tell if a parenteral is pyrogen free?
rabbit test LAL test (limulus amebocyte lysate)
How does a rabbit test work?
take 10-20 rabbits and give them the substance to be tested a change in rectal temp of half a degree C in 1 rabbit ot sum of 1.4 C in 5 rabbits = bad batch with pyrogens in it (caused fever in rabbits)
How does a LAL test work?
if substance has pyrogens, an enzyme complex from horseshoe crab red blood cells will coagulate in the presence of pyrogen done in a petri dish; if coagulation happens, there is a pyrogen
Which pyrogen test is more sensitive to endotoxins?
LAL test better than rabbit test
What is a disadvantage of both the rabbit test and the LAL test?
Rabbit= labor intensive LAL= very expensive
What is the smallest particle that the human eye can see?
>50 micrometers reflective particles of glass 25 micrometers
How can we detect particulate matter in a parenteral?
light box (electronic liquid-borne particle counter with a light-obscuration sensor) swirl contents against a dark and light background
What is the risk of having too many particulates in a parenteral?
thrombus and embolus
What can help reduce particulate matter after a prep has already been made?
line filter given to nurse to place on line
What is the %error allowed for the drug content in a parenteral?
How much excess volume is in a parenteral product?
What specific information must be on a label for a parenteral?
What are the two ways that powders are made for reconstitution?
What additive is prohibited in parenterals?
What agents should be used in smallest amounts possible or not at all (restricted use)?
buffers stabilizers preservatives
What does 'hermetic' mean?
sealed container that should not be opened
What is the only parenteral product that may be opened? (the exception to hermetic containers)
an irrigation bottle with a screw top
T/F: Water for Injection (WFI) is not required to be sterile.
T/F: Water for Injection must be pyrogen-free.
T/F: Water for Injection is used for parenterals that will undergo final sterilization.
T/F: Water for Injection contains antimicrobial agents.
T/F: Sterile water for injection contains antimicrobial agents.
T/F: SWFI is used for reconstituting sterile powders or for parenteral admixture.
T/F: Sodium chloride injection (Normal saline injection) contains antimicrobial agent.
T/F: Sodium chloride injection is sterile and pyrogen-free.
T/F: BWFI (bacteriostatic water for injection) can be used for newborns.
T/F: BWFI contains antimicrobial (bacteriostatic) agents.
T/F: BWFI can be toxic if used in too high of volumes.
What is the max amount of BWFI that you will find in a vial?
T/F: Benzyl alcohol is a common bacteriostatic agent found in BWFI.
What is Ringer's injection?
sterile solution of: sodium chloride calcium chloride potassium chloride in a concentration similar to our body fluids used as a vehicle or electrolyte replenisher
What is Lactated Ringer's?
NaCl + KCl + CaCl 2 + lactate(sugar) offers more calories than regular ringer's
What is D5W?
sterile isotonic solution of dextrose used to hydrate patients without adding salts
What are some non-aqueous injections?
USP grade: glycerin propylene glycol polyethylene glycol alcohol fixed vegetable oils like: sesame oil peanut oil safflower oil canola oil cottonseed oil corn oil
What is the #1 USP grade oil used for IVFEs?
What are some characteristics that USP grade nonaqueous parenteral products should possess?
syringeability nontoxic non-sensitizing non-irritating used as solvents for drugs w/ limited water solubility or that are susceptible to hydrolysis
What are some characteristics that USP grade fixed veg. oils for parenteral use must possess?
remain clear when stored under refrigeration must not contain mineral oil or paraffin label must list the specific oil used for IM injections mostly
What ingredients should be added to parenterals only if necessary to increase stability or effectiveness?
co-solvents buffers antioxidants solubilizers preservatives
What can the manufacturer do to an injectable vial to prevent chemical reactions with oxygen (oxidation)?
remove air in head space of vial with nitrogen or CO
Which type of glass is used to contain highly reactive drugs?
Type 1 (boracylicate)
Which type of glass is not permitted for containing parenterals?
What are some disadvantages of glass containers?
heavy easily breakable bulky for storage
What are the 3 types of plastics used for parenteral bags and supplies?
Polyethylene (PE) Polypropylene (PP) Polyvinyl chloride (PVC)
Which plastic cannot be autoclaved?
T/F: multiple dose containers contain antibacterial preservatives.
T/F: ampules contain antibacterial preservatives.
T/F: single-dose containers can be resealed and used again.
T/F: multi-dose containers can be resealed.
T/F: single dose containers can be large or small volumes.
T/F: multiple dose containers are usually no more than 30 mL.
true; to avoid too many penetrations/uses and too much antibacterial agent needed
What type of containers do drugs that are highly sensitive to hydrolysis go in?
Advantage bags/snap bags/nurse activated systems
T/F: it is common practice and permitted to have a slight excess in volume compared to what the label says.
What is the typical amount of fluid range that makes an LVP?
150-1000mL single dose only!
T/F: SVPs can be used for direct injection into vein, subQ, IM, etc.
T/F: LVPs are used for IV infusion only.
T/F: LVPs contain antibacterial preservatives.
false; do not!
What are some types of LVPs?
Maintenance therapy Replacement therapy Fluid requirement Electrolyte requirement Caloric requirement Parenteral nutrition Blood replenishment irrigation solutions dialysis solutions pellets or implants
What is a maintenance therapy?
for patients entering or recovering from surgery or unconscious
What is a replacement therapy?
for patients with heavy loss of fluid and/or electrolytes due to severe diarrhea or vomiting
What is a fluid requirement?
when water is administered in a solution with Dextrose or electrolytes (avoids hemolysis)
What is an electrolyte requirement?
Potassium: for hypokalemia after a severe burn, GI disease, acute alcoholism, poor nutrition Sodium: for hyponatremia during excessive sweating, diarrhea, use of some diuretics Chloride: maintains acid-base balance Calcium, Magnesium, Bicarbonate, Acetate, Lactate, etc.
What is a caloric requirement?
D5W is used to maintain basal caloric requirements, reduce a calorie deficit, and minimize breakdown of proteins
T/F: you can give up to 10% D5W to a patient that needs more calories.
T/F: IVFEs or parenteral nutrition must be given into the central vein of a patient.
What is another term for parenteral nutrition?
What is parenteral nutrition?
an infusion of large amounts of basic nutrients like amino acids, dextrose, electrolytes, vitamins and fats for patients unable to get oral or enteral nutrition
T/F: D5W can be given into a peripheral vein.
T/F: irrigation solutions are used for injection.
false; only for washing debris
T/F: Pellets/implants are a form of parenteral dosage form.
T/F: a pellet or implant does not need to be sterile before it is implanted in the body.
T/F: CFCs are not allowed in pharmacy anymore due to their harmful effects.
False; allowed, but manufacturer must prove why another gas can't be used
How are aerosols completely different from any other dosage form?
the dose is not dependent on the patient, it is dependent on the container, valve and propellant
What is the definition of an aerosol?
dispersion of pressurized liquid and/or solid drugs in a gaseous medium (propellant)
T/F: an aerosol can be made of a gas within a gas.
What forms can an aerosol be made of?
cream ointment liquid gas powder gel foam
T/F: aerosols can come in glass, plastic, or metal containers.
What is the main difference between an aeorosol for inhalation and one for dermatologic therapy?
an aerosol for inhalation has much smaller particles in the form of a fine liquid mist or fine solid a dermatologic aerosol is made of coarse particles and is less critical for efficacy
What is the most common aerosol dosage form?
aerosols for inhalation (MDIs)
What size should a particle be if we want the aerosol to reach the trachea and bronchi only?
What size should a particle be if we want the aerosol to reach the bronchioles?
What size should a particle be if we want it to reach the alveolar ducts and the alveoli (deepest part of lungs)?
less than 2 micrometers
What determines the amount of drug received by a patient when they use an MDI?
the dual valve chamber
What happens when the actuator on an MDI is released?
the dose chamber is refilled for the next dose
T/F: there are vaginal and rectal aerosols.
What are two examples of foam or cream aerosols?
vaginal and rectal
What is an example of a translingual aerosol and where should it be administered?
Nitrolingual goes under and on the tongue
What are all the different categories of aerosols?
dermatologic inhalation vaginal rectal translingual space surface
What are some advantages of aerosols?
contents do not become contaminated drug is not affected by oxygen, moisture, or light sterility is maintained site of action can be controlled well exact dose every time drug delivered in a clean way can provide cooling effect on skin don't have to touch the affected area to get a uniform application of the drug
What are the 2 main components of an aerosol?
product concentrate propellant
T/F: a propellant can be either a liquid gas or a non-liquefied compressed gas.
Why are CFCs bad?
they reduce ozone in the atmosphere and increase UV light reaching the earth
How do CFCs propel a drug product out of a canister?
they are nonpolar and organic, so they oppose the liquid and push it out
What happens if a CFC is combined with alcohol?
it forms HCl-- very bad for the patient
T/F: CFCs are generally liquids when compressed or cooled below boiling point, but are gases at room temp.
What dual role do CFCs serve?
propellant solvent or vehicle
What part of CFCs makes them so bad?
the 'fluor' in fluorinated hydrocarbons such as chlorofluorocarbon (CFC)
T/F: CFCs have been prohibited for general use since 1978, but are still allowed for pharmaceutical use.
What are some examples of non-liquefied gases used in aerosols?
nitrogen nitrous oxide carbon dioxide
Which non-liquefied gas is completely insoluble in the concentrate?
What gas(es) are slightly soluble in the concentrate?
nitrous oxide and carbon dioxide
Which non-liquefied gas is typically used to replace oxygen in a parenteral vial and is taseteless, odorless, inert and protects from oxidation?
Which two gases are expelled with the product concentrate to produce a spray or a foam?
nitrous oxide carbon dioxide
What is the main principle of how an aerosol works?
the canister is under pressure at all times when the valve (actuator) is pushed, the vapor pressure forces the liquid phase up through the valve and pressure is released after some of contents is expelled, the equilibrium between the liquid and gas phases is reestablished
What are the 3 types of aerosol technology systems?
2 phase system 3 phase system compressed gas system
What are the 2 phases in a 2 phase system for aerosols?
1. vapor phase (gas propellant) 2. liquid phase (mix of liquified gas + product concentrate)
What are the 3 phases in the 3 phase system for aerosols?
1. aqueous product concentrate 2. vapor phase (water-immiscible gas propellant) 3. water-immiscible liquefied propellant in bottom of container
T/F: only 2 phase and 3 phase systems require shaking before use, not compressed gas systems.
T/F: compressed gas systems are under much higher pressure than 2 or 3 phase systems.
T/F: there is only about 20-30% of product concentrate in a compressed gas aerosol system and the remainder is gas.
What is a compressed gas only system for aerosols?
the pressure of compressed gas (usually CFC) in the headspace of the container forces the drug up the dip tube and out of the valve
T/F: compressed gas systems for aerosol use do not have any harmful side effects.
What is the main side effect that you might see with use of a CFC compressed gas system for aerosols?
cardio effects because this gas also has an affinity for the heart and lungs
What are the 2 methods used to prepare aerosols?
cold filling pressure filling
Which method should not be used to make aerosols that contain aqueous product concentrate?
Explain cold filling for an aerosol.
cool container to -30 or -40 F cool product concentrate to -30 or -40 F as well liquefy propellant and also cool to same temp as above add cold concentrate to cold container add liquefied propellant assemble valve parts
What aerosol method is most commonly used to prepare pharm. products?
Why is pressure filling the most common method used to prepare aerosols?
because there is less moisture contamination and less propellant is lost in the process
Explain pressure filling method for aerosols.
add product to container assemble valve evacuate air by using a vacuum add liquefied gas under pressure
What are some aspects of an aerosol that need to be tested?
leaks weak spots in container valve accuracy reproducibility of dosage drug concentration spray pattern particle size particle distribution in spray
T/F: it is acceptable for a patient to spray a facial topical aerosol directly onto their face.
false; spray into hand first! also clean affected area first.
T/F: written instructions are all that needs to be given to a patient who is receiving an aerosol.
false; verbal too
T/F: some drugs for inhalation can be used for systemic effects after they are absorbed from the lungs.
true; Oxygen or halothane
T/F: some solutions for inhalation can come in the form of a capsule or ampule.
What are some miscellaneous preps for respiratory administration?
nebulizers humidifiers vaporizers sprays
What is a nebulizer?
an apparatus that produces fine particles for inhalation (a rubber bulb + a glass chamber)
What is the difference between a vaporizer and a humidifier?
humidifier= cool mist vaporizer= mist of hot steam
Which is louder, a humidifier or a vaporizer?
Which is more energy efficient, a humidifier or a vaporizer?
Which one would an elderly person most likely prefer, a humidifier or a vaporizer?
a vaporizer because heats a room and does not deposit minerals on furniture
Which one is free of bacteria and mold, a humidifier or a vaporizer?
T/F: a spray contains a propellant.
What are sprays generally made of and used for?
made of aqueous or oleaginous solutions for topical use on skin or in the nasal-pharyngeal tract
T/F: a spray may or may not have a metered valve.
What is the definition of an emulsion?
a dispersion of immiscible liquids (polar and non-polar together) usually in the form of droplets within the vehicle
T/F: the dispersion medium is continuous.
T/F: the dispersion medium is the internal phase.
What is the emulsifier also known as?
surfactant or wetting agent
What are the different types of emulsions?
O/W W/O liquid semisolid/liquid
What is an example of an oral emulsion?
What is an example of a topical emulsion?
What is an example of a parenteral emulsion?
IVFE (fat emulsion)
What is an example of a semisolid/liquid emulsion?
cream and lotion
T/F: oral emulsions are usually the w/o type.
false; usually o/w in order to hide the oil
T/F: emulsions allow for enhanced absorption because oil as small globules are more digestible and better absorbed.
T/F: emulsions allow us to mask the taste of drugs well.
T/F: the flavoring for an emulsion should go into the internal phase.
false; will do no good there, must be in external phase
T/F: most commercial emulsion bases are w/o.
false; most are o/w
What are 3 examples of w/o emulsion bases?
eucerin nivea cream polysorb hydrate
What are some common emulsifiers?
sodium lauryl sulfate (SDS) triethanolamine stearate wool wax alcohol etc, etc
What are the 3 theories of emulsification?
1) reduction of interfacial tension theory 2) oriented-wedge or electrical double layer theory 3) plastic or interfaciall-film theory
Why do we want to reduce interfacial tension?
because it causes small drops to join or coalesce, forming a larger drop which will break an emulsion
Explain the Reduction of Interfacial Tension theory of emulsification.
2 immiscible liquids are shaken together in order to get the smallest spherical droplets possible use a surfactant, which will lower the interfacial surface tension and break up large globules into smaller ones
Explain the Oriented-wedge/Electrical double layer theory of emulsification.
emulsifier forms layers surrounding either the oil or water globules the emulsifier hydrophilic and hydrophobic portions will orient themselves into each phase, producing electrical forces that repel approaching droplets the phase in which the emulsifier is more soluble will become the external phase
What has a hydrophobic (water hating portion) and a hydrophilic (water loving portion)?
Explain the Plastic/Interfacial Film Theory of emulsification.
the emulsifier surrounds the droplets of the internal phase as a thin layer of film aDsorbed on the surface of the droplets there must be enough film forming material to completely surround each drop of the internal phase
T/F: usually emulsifiers are only used by themselves and not with other emulsifiers.
What type of emulsifier should be used for the initial formation of an emulsion?
one that lowers interfacial tension
What type of emulsifier should be used to maintain the stability of an emulsion?
an oriented wedge emulsifier or an interfacial film emulsifier
What are some examples of carbohydrate emulsifiers?
acacia tragacanth agar pectin
Which emulsifiers are plant derived and natural?
What are some examples of protein derived emulsifiers?
What are some examples of colloidal clays used as emulsifiers?
bentonite magnesium hydroxide aluminum hydroxide
What are the 3 different categories of surfactants?
anionic agents cationic agents nonionic agents
What are some examples of anionic surfactants?
SDS triethanolamine oleate monovalent, polyvalent and organic soaps
What is an example of a cationic surfactant?
What are some examples of nonionic surfactants?
SPAN 40,60,80 Tween 20, 60,80 Myrj 45 Brij 30
For an anionic surfactant, the lipophilic portion is_____ charged?
For a cationic surfactant, the lipophilic portion is ____ charged?
For nonionic surfactants, the lipophilic portion is ____ charged?
no inclination to ionize!
What type of emulsifiers should be used if you want to make an O/W?
carbohydrates proteins colloidal clays or high mol. weight alcohols, depending on what you're making
T/F: colloidal clay emulsifiers can produce o/w or w/o emulsions, depending on which phase has a greater volume.
What type of emulsifiers are used as thickening agents and stabilizers?
high molecular weight alcohols
What type of emulsifier should be used if you wanna make a w/o emulsion for external use?
cholesterol and its derivatives
What type of emulsifier should be used if you wanna make an o/w emulsion for external use?
stearyl alcohol (also a binding agent) cetyl alcohol glyceryl monostearate (also a suspending agent)
Which type of emulsifier should be added to a powder with low solubility or that is so small it will float?
Which type of colloidal clay emulsifier is Wyoming a huge producer of?
What are the 6 methods for preparing emulsifications?
1. beaker method 2. in situ method 3. bottle/forbes bottle/shaking method 4. auxiliary methods 5. wet gum/English method 6. dry gum/Continental method
T/F: alcohol should be added last to a dry gum emulsion.
What is the dry gum/continental method aka?
4:2:1 method 4 ml/g of oil 2 mL/g of water 1 g of emulsifier
What is the hydrocolloid?
the oil + the gum (dry gum method)
In the dry gum method, what is the order of mixing the 3 main ingredients?
oil+gum(emulsifier) then add water all at once
In the wet gum method, what is the order of mixing the 3 main ingredients?
water+gum(emulsifier) then add oil in small portions
Which method of emulsification favors the w/o final form?
wet gum method (because the oil is added last)
Which emulsification method favors the o/w final form?
dry gum method (because water is added last)
In which method of emulsification do you need to hear a cracking sound to know that you have made your primary emulsion?
dry gum method
What is a mucilage?
small quantity of water + gum that is made by trituration in the wet gum method can also be used as a filler for baby food or food for elderly
Which method has a primary emulsion that is creamy and white?
dry gum method
Which emulsification method is a variation of the dry gum method and is used for volatile oils and low viscosity oils?
Bottle/Forbes bottle/Shaking method
Explain the Bottle/Shaking/Forbes bottle method of emulsification.
add emulsifer and volatile oil together and shake in short, rapid movements add water all at once and shake add other aqueous materials in small amounts, shaking after each addition
Which method should be used for synthetic emulsifying agents?
the Beaker method
Explain the Beaker emulsification method.
prepare oil and water phases separately with their dissolved ingredients heat both phases to 60-70 C if needed add internal phase to the external phase and stir remove from heat gentle and periodic stirring to congeal (think of cold cream)
What are some auxiliary methods for emulsification?
hand homogenizer mechanical stirrer (mixers)
What is the in situ soap method for emulsification?
you create a calcium soap (a w/o emulsion) by adding cacium hydroxide solution (lime water) + vegetable oil
When should you use the in situ soap method to make an emulsification?
to reduce surface tension for topical preps
T/F: it is acceptable to add more to the external/continuous phase of an emulsion.
T/F: very small amounts of other things can be added to the internal phase of an emulsion, but extra emulsifier must also be added.
Which phase of an emulsion affects the ending consistency of the product?
the external phase
Which phase of an emulsion affects the emulsifiability of the product?
the internal phase
T/F: a mortar and pestle that are used to prepare an emulsification should have a rough surface.
T/F: when making an emulsification, the aqueous phase should be heated to a few degrees warmer than the oil phase (if heat is used).
What does an HLB value tell you about an emulsifying agent?
it is a number that is indicative of it's
What does HLB stand for and what does it mean?
Hydophile-Lipophile Balance it describes the characteristics of a surfactant based on its chemical structure
T/F: emulsifying agents usually have a hydrophilic and a lipophilic portion with one or the other being more predominant.
T/F: something that is polar will dissolve in water.
What is the typical range of values for an emulsifying agent that likes oil and will be good for making w/o emulsions?
What is the typical range of values for an emulsifying agent that likes water and will be good for making o/w emulsions?
What is the best way to make a stable emulsion?
use more than one emulsifier
an emulsifier with an HLB value between 1-10 is predominantly _____ and less _____.
an emulsifier with an HLB value between 10-20 is _____ and is more ______.
T/F: When blending emulsifiers, the HLB needed can be obtained even if that specific HLB value is not on hand by using alligation.
T/F: the preservative in an emulsion should be concentrated in the aqueous phase.
T/F: parabens are not good preservatives for emulsions.
false; the BEST
T/F: preservatives should be present in the un-ionized state in an emulsion.
true; will be most effective against bacteria
Why do we add antioxidants to emulsions?
to prevent rancidity of oils and fats
What are some common antioxidants used in emulsions?
ascorbic acid (citric acid) butylated hydroxyl-anisole gallic acid sulfites I-tocopherol
Which antioxidant are some patients allergic to and are also used in wines and foods?
sulfites must be aware of patient allergy
"you don't want to be walking around w/ a big cloud of smell around you, unless you are wearing ______" -G
Chanel #5 :)
T/F: flavoring/odorants should be added to the internal phase of an emulsion.
When adding a flavoring oil to an emulsion, when and what should it be added to?
add to surfactants before addition to the aqueous phase you can also add it to a cosolvent like glycerin or ethanol
T/F: oral emulsions need to have a wide mouth opening.
What two statements (labels) absolutely must be on an emulsion?
shake well before use for oral use/for topical use
What do emulsions need to be protected from when they are packaged?
light extreme temps of hot or cold
What feature does a container for an emulsion need that is different from other dosage forms?
extra head space so that it can be shaken well
what is the optimum ratio of oil to water or vice versa?
40% internal/60% external
By decreasing the size of globules in an emulsion, what are you doing?
What can you do if you want to make an emulsion thicker?
add a substance that is soluble in or miscible with the external phase o/w: add a hydrocolloid w/o: add a wax, viscous oil, fatty alcohol or fatty acid
What is another term for coalescence?
cracking or braking
T/F: coalescence is an irreversible process.
true; very hard to get an emulsion back
What is it called when an o/w switches to a w/o or vice versa?
What is it called when the internal phase forms aggregates or globules upon standing. Aggregates may rise to the top or fall to the bottom of an emulsion.
T/F: in an emulsion, 'creaming' is an irreversible process.
false; can be reversed by shaking
What are 3 forms of instability in an emulsion?
coalescence creaming phase inversion
What is a microemulsion?
a biphasic o/w system stabilized w/ surfactants w/ HLB values of 15-18 contains droplets of 100-5000 angstroms (very small)
T/F: a microemulsion is optically transparent.
T/F: vitamin oils like A, D and E are examples of microemulsions.
T/F: IVFEs are not microemulsions.
false; parenteral IVFEs are microemulsions
T/F: microemulsions can be used in patches.
What are some advantages of microemulsions?
more rapid and efficient oral absorption of drugs increased diffusion of drug into the skin can make artificial RBCs can get cytotoxic drugs to cancer cells better
T/F: in transdermal drug delivery systems, the target is the skin.
Where is the most delicate area of our skin?
behind the ear and the testicles :)
What was the first TDDS system to be manufactured?
Transderm Scop (scopalomine)
What type of absorption are we achieving with a TDDS?
What are some factors that influence percutaneous absorption?
physical/chemical properties of the drug condition of the skin vehicle used surface area of the patch time
T/F: patch systems are hard to test.
true; there are no animal models that have skin like we do
Where should you not apply a patch?
to compromised, irritated, or damaged skin
What is main barrier for a patch delivery system (specific)?
What is another name for the stratum corneum?
What is the outermost layer of the epidermis?
stratum corneum/horny layer
What are the 3 layers of the epidermis?
(from outer to inner) stratum corneum stratum lucidum (granulosum) stratum germinativum
What are the 3 main layers of the skin that a drug must pass through?
epidermis dermis subcutaneous
Which layer of the skin do we start to see small, thin blood vessels?
T/F: blood vessels are the largest in the subcutaneous layer of the skin.
What 3 things can we find on the outer layer of our skin all the time, and might effect drug absorption?
In which layer of our skin do we find keratin?
T/F: the stratum corneum lacks continuity and is not a significant factor in drug penetration.
T/F: We have 15-25 layer of cells in the stratum corneum over most of our bodies.
T/F: Drugs do not pass through the stratum corneum by passive diffusion.
false; they do
T/F: the stratum corneum acts like a semipermeable artificial membrane for drug penetration.
Which layer of our skin is the main rate limiting barrier to transdermal drug transport?
the stratum corneum
Which layer of our skin can be considered the 'living epithelium'?
stratum lucidum (granulosum)
Which layer of our skin can be considered the 'living epidermis'?
Which layer of our skin do we want to get the drug to and why?
dermis because it is highly vascularized
Which layer of our skin is a barrier layer with living cells at several differentiated levels?
stratum lucidum (granulosum)
Lipid-rich, non-polar drugs pass through our skin in what way?
Polar drugs pass through the skin in what way?
What is the major route of drug penetration in our skin?
What is it called when drugs pass through hair follicles, sweat glands, and sebaceous glands with minor drug absorption?
What is the only patch that is placed behind the ear (according to Glaucia)?
T/F: patches mimic a parenteral delivery.
How do patches mimic a parenteral delivery system?
they have a similar concentration vs. time curve
T/F: almost all patches have penetration enhancers in them.
What is the molecular weight range that is best for a patch system?
100-800 (400 is the best)
Why are more drugs not in a patch form?
because they don't have a molecular weight between 100-800
What is inunction?
rubbing the skin
T/F: inunction (rubbing) and exercise both increase vasodilation in the skin and may increase the amount of drug released by a patch.
What main factors affect absorption of a drug in patch form into the skin?
physical factors drug chemical factors skin factors vehicle factors
What are some factors that are related to the vehicle when talking about factors affecting skin absorption of a TDDS?
adherence to skin miscibility with sebum action as a moisture barrier
What are some factors that are related to the skin when talking about affecting skin absorption of a TDDS?
intact vs. broken skin surface area applied site of application (thin horny layer)
What are some factors that are related to the drug when talking about affecting skin absorption of a TDDS?
concentration particle size molecular weight solubility in water and oil attraction to the skin
What are some physical factors that affect skin absorption of a TDDS?
rubbing exercise vasodilation time of contact with the skin multiple application site of application
What are some chemical methods used to enhance percutaneous absorption of a TDDS?
use a carrier mechanism modification of lipids in intercellular channels modification of stratum corneum's hydration reduction of stratum corneum's resistance
What are the 3 types of percutaneous CHEMICAL enhancers?
solvents miscellaneous amphiphiles
What are some examples of solvents (penetration enhancers for TDDS)?
water alcohol (methanol, ethanol) alkyl methyl sulfoxides (DMSO) pyrrolidones Laurocapram (Azone) acetone dimethyl acetamide dimethyl formamide
What are some examples of amphiphiles (penetration enhancers for TDDS)? Hint: amphi= on both sides
anionic surfactants (docusate, SDS) cationic surfactants (quaternary ammonium salts) amphoteric surfactants (lecithins, cephalins, alkyl bentamines) nonionic surfactants (monoglycerides, diglycerides, triglycerides) fatty acids and alcohols (PEG, sorbitan, cetyl alcohol, stearyl alcohol, lauryl alcohol)
What are some examples of miscellaneous penetration enhancers for TDDS?
What are some physical methods that enhance percutaneous absorption of a TDDS?
What is iontophoresis?
delivery of charged chemicals across the skin using electrical field some patches have a device that passes a current through the skin Ex: lidocainem, hormones, amino acids, verapamil, propanolol
What is sonophoresis?
high-frequency ultrasound facilitates drug penetration through the stratum corneum a microchip embedded in the patch Ex: salycylic acid for warts, lidocaine also, hydrocortisone
T/F: a patch is a rate-controlled system.
T/F: patches deliver a drug at a controlled rate to intact skin without buildup in the dermal layers.
T/F: patches release the drug promptly from the system into the s. corneum for penetration into the general circulation for systemic effects.
What is a therapeutic advantage of a patch that other dosage forms lack?
no drug is lost they cause occlusion of the skin so there is only a 1-way flux of drug
Patches should cause no irritation or sensitization to the skin due to the _______, ______, or _________?
drug, vehicle, or adhesive used
Which dosage form is 'paradise for compliance' according to G?
What are some advantages of a patch?
patient compliance avoid GI difficulties substitute for oral administration avoid first pass effect substitute painful parenteral administration provide multi-day therapy with a single application drug's effect can be terminated by removing the patch fast ID during an emergency (no medical record needed) convenient
What are some disadvantages of a patch?
unsuitable for irritating or sensitizing drugs or highly sensitive people can cause contact dermatitis only relatively potent drugs can be made in a patch technical difficulties during prep of a patch can contaminate others if not disposed of properly
What are some examples of patches that are monolithic/matrix systems?
estradiol (Climara, Alora, VivelleDot) OrthoEvra Lidoderm
What are some examples of patches that are membrane-controlled/reservoir systems?
Transderm-Scop Nicotine (Habitrol) Estraderm Catapres TTS Duragesic
T/F: Monolithic/Matrix system patches can be cut.
T/F: Membrane-controlled/reservoir system patches can be cut.
What patch is used once a day for the prophylaxis of angina pectoris?
NitroDur, Minitran, Transderm-Nitro
What patch is used to treat hypertension?
Which patch is used to treat urinary incontinence?
Which patch is used to treat Alzheimer's?
Which patch is used to treat Major Depressive Disorder?
Which patch system allows the skin to control the rate of absorption of the drug?
Which patch system usually has excess amounts of drug?
Which patch system delivers uniform quantities of drug to the skin over a period of time?
Which patch system contains drug (liquid or gel) that remains saturated and the release of the drug is constant?
Which patch system allows the patch itself to control the rate of delivery of drug with a rate-controlling membrane?
T/F: the adhesive layer (glue) of a membrane-controlled patch contains an initial priming dose.
Which patch system maintains a wide range of plasma concentration over which the drug is effective, but never toxic?
Which patch system has the drug blended or dissolved in a polymer matrix?
Which patch system is made of a release/film layer, an active drug plus adhesive layer, and a third layer of backing film?
Define a suspension.
a 2 phase system of finely divided drug particles (suspensoid) mixed into a vehicle (dispersion medium)
What is the study of flow?
What are some advantages of a suspension?
chemically stable easy to swallow flexible administration range of doses can be given good bioavailability can mask the bad taste of a drug
How can suspensions be administered (what are all the different ways)?
oral topical ophthalmic rectal nasal otic/aural parenteral (IM)
What are the ready to use commercial suspensions called?
What are the commercial suspensions that are in powder form and need to be reconstituted called?
"for oral suspension"
What are some features of suspensions?
therapeutic efficacy chemical stability esthetic appeal resuspendability thixotropy
T/F: thixotropy is desirable in a suspension for increasing physical stability.
T/F: the order of mixing the ingredients of a suspension is not important to its stability.
false; it is important
T/F: additives like flavoring, coloring, and preservatives should be added to the dispersed phase of a suspension.
false; to the dispersion medium
A ______ particle size equals slower sedimentation rate?
An _______in vicosity equals slower sedimentation rate?
Why do we not want too much of an increase in viscosity of a suspension?
will make it too hard to pour
A ____ density particle equals a faster sedimentation rate?
What is the most important consideration when referring to the dispersed phase of a suspension?
What are some ways to reduce the size of particles for a suspension?
comminution dry milling micropulverization fluid energy grinding (jet milling, micronizing) spray drying
What is the best range of particle size for a suspension?
Which method of reducing particle size makes particles which are 10-50 micrometer and are used for oral and topical suspensions?
Which method of reducing particle size makes particles that are less than 10 micrometers and are used for ophthalmics and parenterals?
fluid energy grinding (jet milling)
Particle ______ affects caking?
What shape of particles are more stable in a suspension?
symmetrical barrel shaped = more stable than asymmetrical needle shaped
_______ cake upon standing and cannot be redistributed in a suspension?
needles (needle shaped particles)
How can we avoid caking in a suspension?
using a flocculating agent
What is a floc or floccule?
a loose aggregate of particles held together by weak particle-particle bonds less prone to caking settle faster than fine particles break up easily and can be redistributed readily with agitation
What are some common flocculating agents?
clays (bentonite magma) electrolytes like KCl and NaCl surfactants change the pH of the dispersed phase
T/F: viscosity is inversely related to sedimentation in a suspension.
The ________ ______ supports the suspensoid in a suspension?
_______/________ agents help to suspend the suspensoid and provide structure in a suspension?
What are some common suspending agents?
xantham gum bentonite (also a flocculator) polyvinyl pyrrolidone microcrystalline cellulose methylcellulose carboxymethylcelllulose
How do you make a sustained release suspension?
the drug is complexed with ion exchange resins this complex is then coated with ethyl cellulose
What is a Pennkinetic system?
when a drug is complexed with ion exchange resins ex: Tussionex extended release suspension
T/F: you can make an extended release suspension by crushing an ER tablet and adding it to other ingredients.
When formulating a suspension for a newborn, what should not be included? (4 different things)
coloring flavoring preservatives (benzyl alcohol, propylene glycol) alcohol (includes Aromatic Elixir, NF)
What can benzyl alcohol do to a neonate if it is used in a prep?
cause Gasping syndrome- multiple organ dysfunction and death
What can propylene glycol do to a neonate if it is used in a prep?
cause seizures or stupor
What can alcohol do to a neonate if it is used in a prep?
cause CNS depression alter liver function gastric irritation
What 3 things should be considered when packaging a suspension?
wide mouth container air tight, light resistant container adequate head space for thorough mixing
What 3 things should be considered when talking about storage of a suspension?
keep at room temp or refrigerated protect from freezing protect from excessive heat
When labeling a suspension, what should absolutely go on the labels?
shake well before use how to store (room temp, fridge) external or internal use BUD
When telling your patient about the suspension, what 2 things do you need to make sure you mention?
give them the correct measuring tool, show them how to use it tell them to watch for color/consistency changes in the suspension during use
_____ are semisolid systems consisting of dispersions of small inorganic particles or large organic molecules interpenetrated by a liquid?
______ are semirigid systems in which the movement of the dispersed medium is restricted by an interlacing 3-D network of particles or solvated macromolecules of the dispersed phase? (second definition by USP)
_____ are excellent drug delivery systems for oral, topical, nasal, vaginal, rectal use and are compatible with many different drugs?
T/F: gels are relatively easy to prepare and are very efficacious.
What are some examples of alcohol penetration enhancers?
methanol ethanol propanol octanol
What are some examples of fatty acid penetration enhancers?
stearic acid myristic acid oleic acid
What are some examples of fatty alcohols for penetration enhancers?
cetyl alcohol stearyl alcohol myristyl alcohol
What are some examples of some fatty acid esters for penetration enhancers?
isopropyl myristate isopropyl palmitate
What is an anionic surfactant that is used for a penetration enhancer?
What are some polyols that are used as penetration enhancers?
propylene glycol glycerol polyethylene glycol
What are some cationic surfactants used for penetration enhancers?
benzalkonium chloride cetylpyridinium chloride
What is an amphoteric surfactant used as a penetration enhancer?
What are some nonionic surfactants used as penetration enhancers?
What is imbibition (gels)?
taking up of a liquid with no increase in volume
T/F: some gels may be clear as water, while others might be turbid.
T/F: most gels are water-washable, water-solublem, water-absorbing and greaseless, but some have continuous phase alcohol or oleaginous.
What are some common preservatives used in gels?
benzalkonium chloride (also a cationic sufactant/penetration enhancer) sodium benzoate methylparaben propylparaben
What is the normal concentration of gelling agent in a prep?
What is a single-phase gel system?
a gel that contains linear or branched polymer macromolecules that dissolve in water and have no apparent boundary with the dispersing medium
What is a two-phase gel system?
a gel that contains small, discrete particles these gels are thixotropic if the particles are larger, it is called a magma
What is a magma or milk?
a two-phase system with large particles or floccules of small, distinct particles ex: Bentonite Magma, NF
what are some gelling agents?
acacia pectin starch tragacanth xantham gum alginic acid (seaweed) gelatin animal/vegetable fat: lard, cocoa butter bentonite veegum CMC carbomer resins PEG ointment PVA petrolatum, mineral oil, plastibase
What is a neutralizer (for gels)?
it thickens the gel after the gelling agent is dispersed ex: triethanolamine sodium hydroxide sodium carbonate ammonia borax potassium hydroxide