Compounding Flashcards
Extemporaneous Compounding
- on demand preparation of a drug product
- according to a physician’s prescription
- meets the unique needs of an individual patient
Manufacturing
-production or processing of a drug in a LARGE quantity by various mechanisms
Reasons for Compounding
- pediatric patients require diluted strength
- patients needing an oral solution or suspension of a product that is only available in another form
- patients with sensitivity to dyes, preservatives, or flavoring agents found in commercial formulation
- dermatological formulation with strengthened or diluted concentrations of commercially available products
- specialized dosages for therapeutic drug monitoring
- care for hospice patients in pain management
- compounding for animals
U.S. Pharmacopeia (USP)
- established in the 1906 Pure Food and Drugs Act
- federal authority to set standards pertaining to pharmacy compounding
- develops standards where various topics are grouped into “chapters”
- publishes its standards in the resource book called the USP/NF (national formulary)
USP/NF
- chapters are assigned numbers
- chapters numbered below 1000 are legally enforceable by the FDA
- USP/NF has over 60 chapters
- USP also publishes monographs of the most commonly compounded preparations used in practice
Monographs
Recipes
Chapter <795>
- Pharmaceutical Compounding - Nonsterile Preparations
- published in 2000
- enforceable
Chapter <797>
- Pharmaceutical Compounding - Sterile Preparations
- became official in 2004
Chapter <661>
Containers
Chapter <1075>
Good Compounding Practices
Chapter <1150>
Pharmaceutical Stability
Chapter <1151>
Pharmaceutical Dosage Forms
Compounding Regulations Applies To
- Personnel
- Facilities and Equipment
- Ingredient standards
- Quality Assurance and Quality Control
- Packaging and Storage
- Documentation and Record Keeping
ACS Reagent
- American Chemical Society
- high purity
AR
- Analytical Reagent
- very high purity
HPLC
-High Pressure Liquid Chromatography
-very high purity
-used in high pressure chromatography
(used in examining drugs/chemicals found in blood)
Formulation Record
-formulations and procedures (i.e. recipes) for what should happen when a formulation is compounded
Compounding Record
-record of what actually happened when the formulation was compounded
Standard Operating Procedures (SOPs)
-equipment maintenance, equipment calibration, handling and disposal of supplies, etc.
Material Safety Data Sheets (MSDSs)
-ingredients records with certificates of purity
Freezer Temperature
-20 C to -10 C
-4F to 14F
Protect from Freezing Temperature
Store above 0 C
32F
Cold Temperature
Any temperature not exceeding 8 C
Refrigerator Temperature
Between 2 C and 8 C
Cool Temperature
Between 8 C and 15 C
Room Temperature (RT)
Temp in the work area
Controlled RT
Thermostatically controlled at 20C to 25C
Warm Temperature
Between 30C and 40C
Excessive Heat Temperature
Any temperature above 40C
Stability
The extent to which a dosage form retains the same properties and characteristics that it possessed at the time of its manufacture.
Expiration Date
The date until which the manufacturer can guarantee the safety and potency of a drug product’s stability.
Beyond Use Dates
Used for compounded preparations, generally in the order of “days” or “months”.
Shelf Life
Length of time a packaged drug will last without deteriorating.
Non-aqueous liquids and solid formulations beyond use dates
- if the source of the active drug is a manufactured drug product, the beyond use date is NOT LATER THAN 25% OF THE TIME REMAINING UNTIL THE DRUG PRODUCT’S EXPIRATION DATE, or 6 months, whichever is earlier
- if the source of the active drug is a USP or NF substance, the beyond use date is not later than 6 months
Water Containing Formulations Beyond Use Dates
-when prepared from ingredients in solid form, the beyond use date should be no later than 14 days when stored at cold temperature
For all other formulation beyond use dates
-the beyond use dates is no later than the intended duration of therapy or 30 days whichever is earlier
Measuring Equipment
- balance
- weights
- weighing containers
- volumetric glassware (graduates, pipets, flasks, syringes)
Molding Equipment
- hot plates
- suppository molds
- capsule shells,
- ointment slabs
Mixing Equipment
- beakers
- Erlenmeyer flasks
- spatulas
- funnels
- sieves
- mortar and pestle
Packaging Equipment
- prescription bottles
- capsule vials
- suppository boxes
- ointment jars
Class “A” Balance Scale
- two pan torsion balance that uses both internal and external weights
- weights go on the right pan and powder on the left pan
- sensitivity: up to 6 mg
- capacity: 120 mg to 60 gms (60,000 mg)
- degree of error: 5%
- weights: 1 gm to 50 gms
- fraction weights: 10 mg to 500 mg
- electronic or analytical balance
Using a Balance
- Place on a level surface in a draft free area
- Use clean weighing papers or boats
- Must be readjusted after a new paper or boat has been placed on the pan
- Arrest the balance before adding or removing weight
- Use a spatula
- Clean the balance
Using an Electronic Balance
- Keep balance where it will not be moved
- Turn the leveling feet
- Turn on the balance
- First use of the day, check internal weight calibration
- Remove top ring of the draft shield. Place weighing boat in the center
- Add ingredients
- Clean spills with a lint-free towelette
- Turn off balance at the end of the day
Using a Prescription Balance
- Lock the balance by turning the arrest knob
- Set the internal weights to zero
- Unlock the balance and level it left to right
- Lock the balance. Place a weighing boat or paper
- Unlock the balance by releasing the arrest knob
- Lock the balance and place the required weights in the boat
- Unlock the balance and note the shift of the pointer
After an accurate measurement is made, check your work.
Reason for Accurate Weighing
-weighing of the product is an essential part of the compounding process
-weighing the exact amount is essential in compounding for several reasons:
~the product cannot be “checked” for content once mixed
~the quantities weighed out are often very small, and a slight overage could mean a serious overdose for the patient
Spatulas
- used to transfer solid ingredients or prepare ointments and creams or loosening material from the surfaces of a mortar and pestle
- types: stainless steel, hard rubber, plastic
Spatulation
- mixes powders using a spatula
- mixing can be done in a mortar, on an ointment slab, or in a plastic bag
Mortar and Pestle
- the coarser the surface of the mortar and pestle, the finer the triturating, or grinding, that can be done
- types: glass, wedgewood, porcelain
Trituration
The process of grinding powers to reduce the particle size
Compounding Slab
-an ideal surface for mixing compounds because of its nonabsorbent surface
Levigation
Technique used to reduce the particle size of a powder drug by triturating it with a solvent in which the drug is insoluble.
Volumetric Equipment
- graduates
- flasks
- pipets
- syringes
- droppers
- oral syringes
Volumetric Equipment - Graduated Cylinders
- cylindrical and cone shaped
- used for measuring and transferring liquids
- available in sizes ranging from 5 ml to 4000 ml
- when measuring small volumes, such as 20 ml and less, use a syringe or pipet
Selecting a Graduated Cylinder
-choose the smallest one capable of containing the volume to be measured
-RULE: Avoid measurements of volumes that are below 20 percent of the capacity of the graduated cylinder.
(example, a 100 ml graduated cylinder cannot accurately measure volumes below 20 ml)
Volumetric Equipment - Syringes
- range from 0.5 ml to 60 ml and in a variety of materials and styles
- contain graduation marks on the barrel for measuring partial volumes
- disposable hypodermic syringe or an oral syringe made of plastic is used for most compounding tasks involving small volumes
- always choose the smallest syringe capable of containing the volume to be measured
Liquid Measurement - Droppers
-used to deliver small doses of liquid medication
-medicine dropper must first be calibrated because
~the drop size will vary from dropper to dropper
~personal factors can also contribute to the inaccuracy of the droppers
Measuring Liquid Volumes
- pour the liquid to be measured slowly into the graduate, watching the level of the liquid in the graduate as you do so
- if the liquid is viscous, or thick, then you should attempt to pour it toward the center of the graduate to avoid having some of the liquid cling to the sides
Liquid Measurement - Oral Syringes
- available for accurately administering liquid medications to the patient
- have tips that are larger than tips on hypodermic syringes so needles cannot be placed on these syringes
- after the dose is drawn into the syringe, a cap is placed on the tip to prevent leakage and prevent contamination
- oral syringes can be used with a device called adapt-a-cap
Adapt-a-cap
Oral syringe cap that screws onto the bottle containing the liquid, and the oral syringe is fitted into the other side of the cap
Mixing Powders - Geometric Dilution
When mixing powders of unequal size, the smaller volume is mixed (triturated) with an equal volume of the other. That mixture is then mixed with an equal volume of the larger volume of powder. This process is repeated until the mixture is completed.
Solutions
- most commonly compounded product
- clear (but not necessarily colorless) liquids in which the drug is completely dissolved
- solubility of the drug must be known before attempting to dissolve it in a solution. If drug is not soluble in a vehicle, then no amount of mixing will help
- some solids need to be triturated before mixing in a solution
Suspension
-two phase system consisting of a finely divided solid dispersed in a liquid
Flocculating Agent
Electrolytes used in the preparation of suspensions to form particles that can be easily redispersed
Thickening Agent
Ingredient used in the preparation of suspensions to increase the viscosity of the liquid
Very Soluble
<1 ml of solvent
Freely Soluble
1-10 ml of solvent
Soluble
10-30 ml of solvent
Sparingly Soluble
30-100 ml of solvent
Slightly Soluble
100-1000 ml of solvent
Very Slightly Soluble
1000-10,000 ml of solvent
Practically Insoluble
> 10,000 ml
Flavoring Additives
The human tongue contains about 10,000 taste buds which distinguish salty, bitter, sour, and sweet tastes
Sweeteners
Colorless, odorless, soluble in water, pleasant with no “after-taste”, and stable over a wide pH range
Coloring
- not required in every formulation
- contraindicated in all sterile solutions (never added)
- dark colors, such as dark purple, navy, black, and brown may also be rejected because they are often associated with poisons
Freely Miscible
Alcohol and Water
Immiscible
Oil and Water
Emulsions
- unstable system consisting of at least two immiscible liquids
- one is dispersed in the form of small droplets throughout the other
- the other is a stabilizing agent
Emulsifier
- a stabilizing agent in emulsions
- commonly used emulsifying agents include tragacanth, sodium lauryl sulfate, sodium dioctyl, sulfosuccinate, and polymers known as the Spans and Tweens
Primary Emulsion
The initial emulsion to which ingredients are added to create the final product
Mucilage
A wet, slimy liquid formed as an initial step in the wet gum method
Ointments
Used for many different purposes, e.g. as protectants, antiseptics, emollients, antipruritics, kerotolytics, and astrigents.
Antiseptics
Kills bacteria
Emollients
Brings moisture
Antipuritics
Relieves itching
Kerotolytics
Causes skin to peel
Astrigents
Tighten skin
Suppositories - Oleaginous
Primary synthetic triclycerides
Suppositories - Water soluble
Containing glycerinated gelatin or polyethylene glycols (PEGs)
Suppositories - Hydrophyllic
Mixtures of oleaginous and water soluble bases
Suppositories - Cocoa Butter
- theobroma oil
- well known oleaginous base
- room temperature, cocoa butter is a solid
- body temperature, it melts to a bland, non-irritating oil
- no longer the base of choice because preparing suppositories with it is difficult, and the suppositories require refrigeration
Suppositories - Current
- synthetic triglycerides can be used that do not have formulation difficulties of cocoa butter, but are more expensive
- newer bases composed of mixtures of fatty acids that do not have the formulation problems or the expense (e.g. Fattibase, Witepsol)
Water Soluble or Miscible Bases
-glycerinated gelatin or polyethylene glycol (PEG) polymers
-useful for vaginal suppositories
-dissolve slowly to provide prolonged release of active ingredients
-can be formulated by molding or compression in a wide range of hardness and melting points
-do not melt at body temperature, but dissolve slowly to provide a prolonged release of drugs
-available in various molecular weight ranges
~200, 400, or 600 molecular weight are liquids
~molecular weights over 1,000 are solids
Capsules
- hard gelatin capsules consist of a body and a cap which fits firmly over the body of the capsule
- for human use, eight sizes of capsule are available
Capsule Size 000
1.37 ml volume (largest)
Capsule Size 00
0.95 ml volume
Capsule Size 0
0.68 ml volume
Capsule Size 1
0.50 ml volume
Capsule Size 2
0.37 ml volume
Capsule Size 3
0.30 ml volume
Capsule Size 4
0.20 ml volume
Capsule Size 5
0.13 ml volume
Punch Method
Used when filling a small number of capsules
Labeling, Record Keeping, and Cleanup - After Compounding
-product must be labeled with a prescription label, and a careful record of compounding operation should be kept
Labeling, Record Keeping, and Cleanup - Once compounding operation is finished
- equipment and area should be cleaned
- everything should be returned to their proper place in storage
- compounding should never be rushed
- regardless of their apparent stability, all suspensions should be dispensed with an auxiliary label reading “shake well”
- the qs abbreviation means to add “sufficient quantity” to the specified amount
