Spring Exam 1 Flashcards
definition of ointments
USP: semisolid preparations intended for external application to the skin or mucous membranes
–loosely to include: pastes, creams, gels, plasters, poultices (all semisold topicals)
UNG (latin): fatty substance
Specific definition of ointments
- an unofficial specific classification for oleaginous topicals (petrolatum, lanolin or other semisolid oil/grease based preps)
- insoluble in water, not water washable, emollient, occlusive & greasy
Levigation - when is it used?
- powders must be insoluble in UNG base
- to make smooth
- particle size reduction
- minimal amount of base
what is incorporation?
-the processes of combining semi-solid masses
when do you use geometric?
-used with “geometric incorporation”
What are levigating agents?
- often not specified by the prescriber
- SA, not necessary to call physician, use professional judgement
- optional (when not specified)
- always used in a MINIMAL amount!
When are levigating agents used?
- used to facilitate wetting of powders & incorporation efficiency
- powders must be insoluble with the agent
- ideally a low molecular weight version of the base itself or a low viscosity agent compatible with the base
- EXs: mineral oil (use with petrolatum), glycerin (use with PEG) & low molecular weight PEG (use with PEG)
what are solubilization agents?
- should be compatible with the UNG base itself or a suitable adjunct absorption base
- used to facilitate compounding efficiency
- powder must be soluble with the agent
Scenario: a solid, oil-soluble drug to be incorporated with petrolatum
1) dissolve the drug in a minimal amount of mineral oil (on the ointment slab)
2) incorporate (geometrically if needed) oil solution with the petrolatum
Scenario: a solid, water-soluble drug is to be incorporated with petrolatum
1) dissolve the drug in a minimal amount of distilled H2O (usually on the ointment slab)
2) incorporate the solution in a minimal amount of an appropriate absorption base
3) incorporate the above with the petrolatum
Scenario: a solid, powder substance is to be incorporated in an ointment base in which it it NOT soluble
1) levigate the powder in a minimal amount of the base (or levigating agent)
2) incorporate the remaining ointment base with the product
Definition of creams
- USP: creams are semisolid dosage forms containing one or more drug substances dissolved or dispersed in a suitable base
- separate USP classification reserved for water-removable/soluble ointments
- usually not termed an ointment
Definition of gels
USP: gels are semisolid systems consisting of either suspensions made up of small inorganic particles or large organic molecules interpenetrated by a liquid
–> a specific type of ointment
Definition of pastes
USP: pastes are semisolid dosage forms that contain one or more drug substances intended for topical application
-generally high viscosity: stiff, protective property, generally an ointment with >20% w/w powder = paste
How are ointments generally used?
- application to the skin/mucous membranes
- external use only –> exceptions = gels! (mylanta gelcaps, metrogel)
Topical ointments
- applied to the tissues in which the element actually exists
ex) hydrocortisone to a rash
Transdermal ointments
-site of application may be the same but the intent is for the active ingredient to become systemically distributed through absorption into the blood
Ointment uses: emollient*
- a substance that has the ability to help promote the moisturization of tissues that it comes into contact with
- ->*an ointment product may or may not exhibit these properties
is an ointment protective?*
yes! depending on the viscosity & stiffness of the individual base, one may be more protective than the other
Is an ointment a medication vehicle?*
usually yes, but maybe not –> can have active ingredient or are sometimes just used for their protective or emollient properties alone
Use of ointment as a term *(both general & specific)
- general: ointment = semi-solid
* specific: ointment = oleaginous/hydrocarbon base class
what is the ideal ointment?
- spreads easily, compatible with tissues (non-irritating, hypoallergenic, non-abrasive, isotonic)
- smooth & pliable, softens or melts at body temp, easily removed, ready release of medication & doesnt stain skin or clothing
what stability characteristics do we wants in an ointment?
physical, chemical, microbiologic
What are some ointment bases? (5)
1) hydrocarbon/oleaginous
2) anhydrous absorption
3) water in oil emulsion (topical)
4) oil in water emulsion (oral)
5) water soluble
anhydrous
-contains no water
absorbs water
-able to form an emulsion upon the addition of energy
emollient
does it have the ability to promote moisturization of the tissues that is comes into contact with
occlusive
-does it have the ability to shut off the free exchange of gases between the inside & the outside of the skin
Hydrocarbon/oleaginous bases (only listing the YES properties)
- emollient
- occlusive
- greasy
- anhydrous (does not contain water in their pure form)
EAT OLD GREASY ASS
Anhydrous Absorption Bases (only listing YES properties)
- anhydrous
- absorbs water
- emollient
- occlusive
- greasy
EAT OUT ADAMS GREASY ASS
water-in-oil emulsion absorption bases (only listing YES properties)
- absorbs water (somewhat–> since they are already an emulsion, they have some ability to contain water)
- emollient
- occlusive
- greasy
ADAM EATS OLD GREASY
oil-in-water emulsion, water-removable bases (only listing YES properties)
- water washable
- absorbs water (somewhat)
WET ASS
water soluble bases (only listing YES properties)
- water soluble
- water washable
- anhydrous **(does NOT contain water in their pure form but in the manufacturing process, there are some trace amounts of water that are simply there b/c of limitations )
- absorbs water (somewhat)
WET WASH ADAMS ASS
Hydrocarbon/oleaginous bases (detailed info)
-useful when high % of powder (that is insoluble) is to be incorporated into base (10-25% w/w)
Source: petroleum, animal fats/oils, vegetable oils
-wont dry out
Skin Physiology
- pliability of skin is due to moisture content, not oil content
- skin is moisturized from the inside out
- occlusive barrier at skin surface minimizes moisture loss due to evaporation
- washing removed the occlusive barrier
- repeated washing will result in dry skin
- > 20 mins of water immersion = needed to moisturize skin from the outside in
Petrolatum (white or yellow details) H/O bases
- purified mixture of semi-solid hydrocarbons obtained from petroleum
- high viscosity due to high molecular weight only
- will not become rancid (self preserving)
Animal fats/oils (details) H/O base
- lard, suet not commonly used today
- lanolin derivatives (lanolin oil, hydrogenated lanolin)
- may become rancid
Vegetable oils (details) H/O base
- useful as an additive to lower melting point & to soften a product
- may be hydrogenated to promote solidification at room temp (crisco- viscosity partially due to H bonds)
- may become rancid
What is the definition of parenteral?
adj: administered by any way other than through the mouth: applied, for ex, to the introduction of drugs or other agents into the body by injection
para enteron: beside from the intestine
parenteral products must be sterile!!
Definition of aseptic technique
-the ability of personnel to manipulate sterile preparations, sterile packaging components, & sterile administration devices in a way that excludes the introduction of viable microorganisms
Intravenous injections
- peripheral: injection to the arm or leg
* central: use of a central venous catheter)
Intra-arterial (IA)
- uncommon for the administration of medication –> to the high pressure side of the circulatory system
- testing (1st pass kinetics, arterial pressure)
Intramuscular (IM)
-injection to within muscle tissues
Intrathecal (IT)
-injection to the meninges of the spinal cord
Epidural
-injection to the tissues surrounding the spinal cord, not the spinal cord itself
intradermal (ID)
injection within the skin
Subcutaneous (Sc, SQ)
injection beneath the skin
Definition of Sterility
- freedom from all living organisms, an absolute term & no such thing as almost sterile*
- all parenteral & ophthalmic dosage forms must be sterile!
Health status in terms of sterility
-sterile prep personnel should be free from infectious diseases
–> if you have a “cold” and are coughing and/or sneezing stay out of the sterile prep room!
(chills, fever)
Personal Prep for sterile room
- cover both head and facial hair
- remove cosmetics likely to flake
- remove finger and wrist jewelry
Hand-washing rules
- scrub hands & arms to elbows
- plain soap and water not enough for high risk situations (alcohol, chlorhexidine gluconate, iodophors, hexachliphene, parachlorometaxylenol & triclosan)
- use 3-5ml for 30 secs
- wash hands even if gloves are to be worn (leakage rate can be more than 50%) also wash hands after gloves removed
Gloves
- selection based on type of compounding, material durability, reliability, comfort & protection from bacteria or hazardous drug penetration
- for IV room- use SURGICAL gloves
- change ~1 hour
Glove composition**
- latex
- vinyl
- synthetic
Gowns
- should be made of a low-particulate material that protects against bacterial passage and drug permeability
- Tyvek: standard for non-permeable garments
other coverings (shoes & masks)
- shoe covers & sticky mats (change frequently)
- masks: don just prior to working in hood, change each time leaving compounding area, surgical masks offer no protection against inhaling of powdered or aerosolized hazardous drugs
LAFS horizontal flow hood
- filtered air is directed toward the pharmacist/tech from a plenum (and HEPA filter) located at the back of the hood
- most common for general purpose parenteral
BSC Vertical flow hood
- filtered air is directed downward from a plenum (and HEPA filter) located at the top of the hood
- used for chemo therapy
- provides more protection for the pharmacist/tech than does the horizontal hood
Laminar Air Flow
- HEPA Filter removes 99.97% of all particles 0.3 microns or larger
- operate for at least 15 min prior to use –> most institutions require 30 mins
What is the greatest disadvantage of a laminar air flow vibe?
a false sense of security
ISO classifications of particulate matter in room air
(0.5 um and >) theres a whole chart but basically the smaller the number- the higher the air quality
What are pyrogens?
- metabolic products of living organisms, or the dead microorganisms themselves
- chemically: lipopolysassharides, soluble in water but insoluble in organic solvents
- aseptic technique (ideally) prevents the introduction of pyrogens to parenteral products
pharmacologic effects of pyrogens
- vary with the microbial source of the pyrogen & pt receiving the injection
- in man, pyrogenic reaction is fever & chills
- following injection, latent period 45-90 mins, then rapid rise in body temp, chills, headache & malaise
- anaphylaxis
Sources of pyrogens
- water used as the solvent
- containers used in preparation, packaging, storage or administration
- chemicals used in the preparation of the solution
Elimination of pyrogens
-dry heat: for metal and glass containers
-chemically: for solutions (disadvantage: can destroy drugs)
-synthetic filter media: 0.22 micron filter
Best approach: prevent them from occurring
unnecessary factors for when preparing sterile products
talking, laughing, chewing gum, eat/drink
CSP risk levels
-assigned according to relative possibility that a compounded sterile product might become contaminated
*LAFS
laminar airflow system
*BSC
biologic safety cabinet
RABS (CAI & CACI)
-restricted access barrier system
CAI: compounding aseptic isolator
CACI: compounding aseptic containment isolator
*give an example of each ointment base: 1- H/O 2- anhydrous 3- water in oil emulsion 4-oil in water emulsion 5- water soluble
1- petrolatum 2- aquaphor 3- eucerin 4- hydrocphilic ointment 5- polyethylene glycol
**Anhydrous absorption bases
- can absorb up to twice their weight in water 1:1 allowance
- will not dissolve in water
- forms a W/O emulsion when incorporated with an aqueous substance not emulsions by themselves
- useful for incorporation of aqueous liquids and/or water soluble drugs to the emulsions internal phase
**anhydrous absorption base (round 2)
-absorption base means absorptive of water- absorption bases will absorb oil based substances as well
-basic properties very similar to those of oleaginous
bases
Origin: petroleum, animal
Hydrophilic Petrolatum
- hydrophilic due to cholesterol and stearyl alcohol content
- also contains White Wax
Lanolin USP (anhydrous)
- less than 0.35% H2O
- allergens: thumbs down from many dermatologists
Modified lanolin USP
reduced alcohol and detergent content
Other petrolatum variations
aquaphor, aquabase & polysorb
Water-in-oil emulsion absorption bases
- contains water
- already an emulsion
- will absorb aqueous substances on a limited scale
- often used for emollient properties alone, but still suitable for incorporation of drug
examples of water-in-oil emulsion absorption bases
- hydrous lanolin (25-30% H2O)
- cold cream
- rose water ointment
- eucerin
- hydrocream
Oil-in-water emulsion water-removable bases
- generally less viscous than other bases
- often termed “cream”
- since water is the external phase: water washable (advantage), but dries out easily (disadvantage/advantage), vanishing cream
examples of oil-in-water emulsion water-removable bases
- hydrophilic ointment (35-37% H2O, will absorb water, but semi-solid viscosity is eventually lost-lotion)
- vanishing cream
- dermabase
- unibase
Water soluble bases
(ex- PEG)
- wide range of viscosity due to wide range of molecular weight
- polar nature leads to instability & compatibility issues with some drugs
- irritating to mucous membranes
- does not contain oil
- does not contain water
Clean rooms: an environment where contamination is limited/controlled:
particles, organisms & pyrogens
Clean rooms: environmental control:
temperature, humidity & relative barometric pressure
Clean room design (list all the things in there and they supplies they are made from)
- layout: equipment & traffic flow
- walls: epoxy coated
- flooring: seamless, vinyl
- ceiling system: gasketed, t-grid
- filtreation/Air flow: HEPA, positive pressure
- lighting: sealed, gasketed
- easy clean surfaces
Clean room classifications: class 100,000
- particle count not to exceed a total of 100,000 particles per cubic foot of a size 0.5 micron and larger
- and/or 700 particles per cubic foot of a size 5 microns and larger
Clean room classifications: class 100
- particle count not to exceed a total of 100 particles per cubic foot of a size 0.5 micron and larger
- and/or 0.7 particles per cubic foot of a size 5 micron and larger
end product testing: product observation
- container leaks & integrity
- particulates in solution
- solution color, volume and odor
end product testing: retrospective check:
- calculations
- ingredients
- quantities
- containers
end product testing: analytical testing
- evaluates the contents of prepared sterile products
- weight verification (specific gravity), refractometry verification, spectrometry, pH testing, microbial testing
Process Validation
- systematically demonstrates that a process will reproducibly meet its claim
- involves manipulation of microbial growth media according to the aseptic process being validated
- should schedule process under worst conditions
How to validate aseptic processes
- a growth medium: is introduced with a sample of the process being evaluated (product/process sample)
- the medium will support organisms introduced to the process by the operator
- the sample must be a product of the same aseptic process being validated
- should be conducted: at random intervals & without the operator’s knowledge*
more stability: 3 things in green
- the extent to which a Rx preparation remains within specified limits in terms of: chemical composition, physical composition & microbiologic activity/contamination
- at the time of use a medication must be: at the stated potency & safe for administration to the pt
Product stability:
is subject to specific storage conditions & is the primary basis for an expiration date/time
Lyophilzation
- drugs in solution tend to be less stable than those in dry or suspended form
- a process of rapid freezing & drying under high vacuum (sublimation), the product is a dry powder
Sterilization
- 0.22 micron filter
- autoclave
antioxidants
- metasulfite & sulfite ions
- sodium salts, potassium salts (metabisulfite, bisulfite & sulfite)
Inert and semi-inert gasses
nitrogen, carbon dioxide & helium
Particulate matter
-may be present in parenteral products: undesirable, unintentional, potentially harmful to the pt, mobile, undissolved substances
Sources of particulate matter
- IV solution and/or additives: manufacturing process
- packaging components: paper, cardboard
- IV tubing/sets and administration devices
- preparation processes: laminar flow hood, patient bedside
IV fluid incompatibility*
- occurs when a drug is combined with an IV fluid or another drug, to produce by physiochemical means, a product unsuitable for administration to the patient *
ex: phenytoin in D5W (a physical & chemical incompatibility)
Therapeutic classification of incompatibilities
-2 or more drugs administered concurrently, result in undesirable antagonistic or synergistic pharmacologic action - drug/drug interaction
Physical classification of incompatibilities
the combination of ONE or more drugs in solution resulting in compositional change & appearance (change in color, formation of turbidity, precipitation & evolution of a gas)
Chemical classification of incompatibilites
-degradation of drug substances as a result of being in solution & as a result of being in contact with other drugs
The greatest single factor causing incompatibility between IV fluids and their contents:
variations in pH, solubility & stability
minimizing incompatibilities
- use freshly prepared solutions whenever possible
- encourage use of as few additions as possible
- study to demonstrate proficiency in IV therapy
- educate MDs/Rns
- be skillfull with reference materials (Trissel’s, Clinical Pharmacology)
Parenteral administration advantages
- fast
- some drugs not effective orally
- uncomplicated admin. where the pt is: uncooperative, nauseous, unconscious NPO
- patient compliance: gives MD control of drug, pt must return for therapy, cant trust some pts to take medications
- correction of fluid/electrolyte imbalance
- TPN administration: when pt is NPO
Parenteral administration disadvantages
- special training required (special procedure, aseptic)
- invasive
- pain
- difficult to reverse
- more expensive
- incompatibilities
IV compatibility idk other green things to know
- -in general, use smallest possible bag
- refrigerate vs room temp
- light sensitivity
- pay attention to manufacture’s codes when provided*
sterility & integrity requirements for sterile IV admixtures
freedom from living organisms, freedom from dead organisms & pyrogens
H2O insoluble
dead organisms, parts of dead organisms & metabolic products of organisms
H2O soluble
lipopolysaccharides, metabolic products of organisms
hypotonic
< 277 mM
isotonic
~277 mM
hypertonic
> 277 mM
where does the central route access?
- major veins
- access to the venous system close to the heart
- superior vena cava, inferior vena cava & subclavian vein (PICC line)
indications for peripheral admin.
- administration of drugs
- administration of fluids (maintain hydration & volume)
- surgery (anesthesia, drugs)
- transfusion
- to maintain or correct electrolyte imbalance
- administration of nutritional solutions
advantages of peripheral admin (with respect to central**
- veins are relatively easy to access
- drugs, solutions and blood can be administered quickly
- administration is easy to see and monitor
Disadvantages of peripheral admin (with respect to central) **
- short term access
- immobilization of the limb
- less forgiving of tonicity extremes
indications for central admin
- large volume fluids
- hypo/hypertonic fluids
- pH imbalanced fluids
**advantages of central admin (compared to peripheral)
1-rapid infusion of large volumes
2-a means of measuring CVP (*central venous pressure)
3-eliminates repeat peripheral venipuncture (decreased vein irritation & vein damage)
4-decrease patient discomfort
**disadvantages of central admin. (with respect to peripheral)
risk of complications: pneumothorax, sepsis, thrombosis/embolism, organ perforation
- decreased in patient mobility
- surgical implant
intra-aeticular
*injection to the joints
intra-synovial
*injection to the joint fluid areas
intraventicular
*injection to the ventricles of the brain
intra-cardiac
*injection to the heart (epi)
Potential complications of IV therapy
- bad news: most medical & pharmacologic interventions present some risk to patient
- parenteral therapies are more likely to have serious complications
- good news: most complications can be prevented or minimized
- precautions
phlebitis
- inflammation of the veins
- can be induced by insertion of VADs vascular access device
- characterized by tenderness, redness, puffiness, hardness & increased temp
- at tip of VAD & in the direction of blood flow
extravasation
- undesirable
- liquids are infused into peripheral space surrounding vein
- misplaced VAD
infiltration
- undesirable
- extravasation fluids are absorbed by surrounding tissues
Extravasation/Infiltration (general signs and symptoms)
-at the IV site: pain, discomfort, burning, feeling of tightness, decreased temp, cant back flow blood, decreased flow rate
Extravasation/Infiltration (drug specific signs & symptoms)
- tonicity & pH extremes (hypo/hypertonic solutions)–> v irritating
- tissue necrosis: chemo, dopamine, epinephrine
infection
local: contaminated IV site and/or tissues near VAD, sterile and non-sterile necrosis & sepsis (tissue destruction)
Systemic: fever, chills, malaise & septicemia
Air Embolism
- an object blocking a blood vessel- blood clot, fat, amniotic fluid, air, other objects –> MI
- > 5ml of air- right ventricle of the heart, cavitation & fatal
Air embolism (signs and symptoms)
-respiratory distress, weak pulse, increased CVP, decreased BP & unconsciousness
Allergic reactions
-histamine release: itching, tearing, runny nose, coughing, wheezing, anaphylaxis
Why the suppository?
1) an alternative administration route for: NPO pts, unconscious pts & infants
2) non invasive: alternative to IV
Why not the suppository?
1) PO vs PR: dignity, comfort, convenience
2) privacy: cant be administered in public
Suppositories
- solid, unit dose, dosage forms intended for administration of medicine via the rectum, vagina, or urethra
- melt or dissolve in the body cavity
- indicated for administering drugs to infants/small children, severely debilitated patients
Local suppositories
-hemorrhoids, itching, infections
systemic suppositories
-analgesics, anti-nausea, anti-histamine
suppository uses
- recal: adult ~2grams (d= 13-7mm, L= 23-35mm) children 1 gram, more pencil shaped
- vaginal-pessaries
- uretheral- bougies
- nasal
- aural (ear canal)
therapeutic uses for suppositories
rectal: local effect, laxation effect, systemic effect
vaginal: fertility
urethral
ideal base for suppositories
-stable, non-irritating, bland, chemically & physiologically inert, compatible with a variety of drugs, melt or dissolve in rectal fluids, solid below 98.6, liquid above 98.6F, not bind or interfere with release of drug substances
Cocoa butter (suppository base)
- Theobroma oil
- does not become rancid, may leak from body orifice since it is immiscible with body fluids
- softens at 30C, melts at 34C
- no longer the base of choice
Fattibase
-preblended suppository base, similar to cocoa butter, no special conditions, good mold release characteristics
PEG
- water soluble
* base of choice when none is specified
Glycerin
- water soluble
- glycerin, gelatin, sodium stearate, water
Fusion
- when the drug/base compound is a suspension: levigation/geometric combination may be necessary
- constant stirring during pour is necessary
- pour at relatively cool temps (high viscosity & longer setting time)
Mold lubrication
- lubrication/release agent should not be miscible with the base
- green soup for cocoa butter & fattibase
- mineral oil for PEG and glycerin
- apply with cotton tip applicator
Compounding considerations for suppositories
- use of water should be avoided!
- accelerate oxidation of fats, increase the degradation of drugs, support bacterial/fungal growth, dissolved drugs may crystallize as water evaporates, viscosity & bitterness.
example of drug drug incompatibilities
**PEG & aspirin, benzocaine*
Rate of drug release: 1-cocoa butter 2-fattibase 3-glycerinated gelatin 4-polyethylene glycol
** 1- 3-7 min 2- 3-7 min 3- 30-40mins 4- 30-50mins
match the drugs with their drug absorption 1-oil soluble 2-water soluble 3-oil soluble 4-water soluble
**1-slow 2-rapid 3-moderate 4-moderate *oily bases will melt, water soluble bases will dissolve*
Calibration value
- the average mass of one pure base suppository cast in the mold
- mold specific, base specific & not drug specific*
Density factor
- the ratio of a unit mass of drug powder to the amount of suppository base displaced by the powder
- not mold specific, is base specific & is drug specific
