Transcript mixing solids and semisolids

CHAPTER 8
COMPOUNDING
CHAPTER OUTLINE
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Compounding
Regulations
Stability & Beyond-Use Dates
Compounding considerations
Equipment
Using a Balance
Volumetric Equipment
Measuring Liquids
Mixing Solids and Semisolids
• Compounding Select Dosage
Forms
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Aqueous Solutions
Syrups
Nonaqueous Solutions
Suspensions
Flavoring
Sweeteners
Coloring
Emulsions & Emulsifiers
Ointments
Suppositories
Capsules
Tablets
• Review
COMPOUNDING
• Chapter Outline
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Compounding
Regulations
Stability and Beyond-Use Dates
Compounding Considerations
Equipment
Using a Balance
Volumetric Equipment
Measuring Liquids
Mixing Solids and Semisolids
Compounding Select Dosage Forms
WHY COMPOUND?
• Pediatric patients requiring diluted adult strengths of drugs
• 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 formulations
• Dermatological formulations with fortified (strengthened) or diluted
concentrations of commercially available products
• Specialized dosages for therapeutic drug monitoring
• Care for hospice patients in pain management
• Compounding for animals
COMPOUNDING
• 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 or device
 Packaging or labeling for re-sale to
pharmacies or practitioners
REGULATION OF COMPOUNDING
• Compounding is regulated by the individual
states’ boards of pharmacy.
• USP-NF has federal authority to set standards
pertaining to pharmacy compounding and
manufacturing.
• Some states accept the USP-NF standards as
their standards. Some states do not.
REGULATION OF COMPOUNDING
• USP-NF is a resource published yearly.
• USP-NF Chapters are assigned numbers
 Chapters numbered below 1,000 are legally
enforceable by the FDA.
 Chapters numbered above 1,000 are
informational chapters.
• Enforcement of USP-NF chapters by the FDA not always clear-cut (jurisdiction resides with
the states)
 Case-by-case basis
REGULATION OF COMPOUNDING
• The USP-NF also publishes monographs
of commonly compounded preparations
 Stability information
 Beyond-use dates
REGULATION OF COMPOUNDING
• USP-NF standards cover
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Personnel
Facilities and Equipment
Ingredient Standards
Quality Assurance and Quality Control
Packaging and Storage
Documentation and Record Keeping
Many more…
DOCUMENTATION AND RECORD KEEPING
• Formulation record
 what should happen when the formula is
compounded
• Compounding Record
 what actually happened when the formulation was
compounded
• Standard Operating Procedures
 equipment maintenance and calibration, handling and
disposal of supplies, etc
• Ingredients Record
 certificates of purity from commercial vendors
 Material Safety Data Sheets (MSDS)
STABILITY AND BEYOND-USE-DATES
• Stability
 The extent to which a dosage form retains the same
properties and characteristics it possessed at the time
it was made
• Expiration date
 The date until which the manufacturer can guarantee
the safety and full potency of a drug
• determined after extensive study of the product’s stability
• Beyond-use dates
 Used for compounded preparations only and are
generally in the order of “days” or “months”
USP-NF RECOMMENDED BEYOND-USE
DATES*
• Topical, dermal, mucosal liquid or semisolid
formulations containing water
 not later than 30 days
• Oral formulations containing water
 not later than 14 days stored at a controlled cold
temperature
• Nonaqueous formulations
 the earliest expiration date of any active principle
ingredient (API) or 6 months, whichever is earlier
*default dates if no other information is available
CONSIDERATIONS IN COMPOUNDING
• Whether to compound
 Is there a commercial product?
• Before beginning
 Are there appropriate personnel and
equipment?
 Prepare a formulation record.
• During compounding
 Compound according to formulation record.
 Complete a compounding record.
• After compounding
 Recheck all work.
 Perform required equipment maintenance.
TYPES OF EQUIPMENT
• Measuring
 balance, weights, weigh
boats, volumetric
glassware (graduates,
pipets, flasks, syringes)
• Mixing
 beakers, Erlenmeyer
flasks, spatulas, funnels,
sieves, mortar and
pestle
• Molding
 hot plates, suppository
molds, capsule shells,
ointment slabs, tablet
molds
• Packaging
 prescription bottles,
capsule vials,
suppository boxes,
ointment jars
BALANCES
• Types
 Class A torsion balance
 Electronic balance
• Reasons to accurately weigh
• One of the most essential parts of the compounding process
• The product cannot be “checked” for content once dispensed to
the patient.
• The quantities weighed are often very small, and a error could
mean an incorrect dosing of the patient.
CLASS A TORSION BALANCE
• A two pan balance that uses both internal
and external weights
• Weights go on the right pan
• Weighted material on the left pan
• Sensitivity: 6 mg or less
• Capacity: 60 g or 120g
• Weights
 brass weights: 1 g to 50 g
 fractional weights: 10mg to 500mg
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
Using a Class A Torsion Balance
1. Place on a level surface in a draft free area.
2. Level front-to-back and left-to-right.
3. Use clean weigh papers or boats with each
new material.
4. Arrest the balance before adding or
removing weight or material.
5. Use a spatula; do not pour from a bottle.
6. Clean balance after use.
USING AN ELECTRONIC BALANCE
1. Place on a level surface in a draft free area.
2. Level front-to-back and left-to-right.
3. Turn on the balance; if first use of the day, check
internal weight calibration.
4. Use clean weigh papers or boats with each new
material
5. Use a spatula: it may be necessary to remove the
draft shield to introduce or remove material.
6. Clean balance after use.
7. Turn off balance at end of day.
VOLUMETRIC EQUIPMENT
•Volumetric Glassware
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graduated cylinders
volumetric flasks
pipets
syringes
burets
•Non-volumetric Glassware
 Erlenmeyer flasks
 beakers
 prescription bottles
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
MEASURING LIQUIDS
• Selecting a liquid measuring device
 Choose the smallest one capable of containing
the volume to be measured.
 Avoid measurements of volumes that are
below 20 percent of the capacity of the device.
• Example: a 100 ml graduated cylinder cannot accurately
measure volumes below 20 ml.
 When measuring small volumes, use a syringe
or pipet.
 Liquids have a meniscus.
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
LIQUID MEASURING DEVICES
• Droppers
• Graduated cylinders
• Single volume pipets
• Calibrated pipets
• Syringes
• Oral syringes
MEASURING LIQUIDS
• Graduated cylinders
• Cylindrical graduates are more accurate than
conical graduates.
• Pour liquids into the center of the graduate.
• Allow 15 seconds for aqueous and
hydroalcoholic liquids to drain from graduate.
• Allow 60 seconds for syrups, glycerin, other
viscous liquids.
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
MEASURING LIQUIDS
• Droppers
 Used to deliver small doses of liquid medication
 Medicine dropper must first be calibrated
• The drop size will vary from dropper
to dropper.
• Personal factors will contribute to
dropper inaccuracy.
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
MEASURING LIQUIDS
Calibrated Pipet
Single Volume Pipets
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
MEASURING LIQUIDS
• Syringes
 Hypodermic or oral
 Range from 0.5 ml to 60 ml
 Always choose smallest size capable of containing
the volume to be measured.
 Oral syringes can be used with an Adapt-a-Cap®.
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without express written permission from the publisher.
MIXING SOLIDS AND SEMISOLIDS
• Mortar and Pestle
 Glass – mixing liquids and semisolids
 Wedgwood
for triturating crystals and large particles
 Porcelain
• Trituration
 The process of grinding powders to reduce
the particle size.
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reproduced, or re-transmitted without express written permission from the publisher.
MIXING SOLIDS AND SEMISOLIDS
• Mixing powders/geometric dilution
• Spatulation
• Ointment slabs
• Levigation
• Electronic mortar and pestle
• Ointment mill
MIXING POWDERS – GEOMETRIC
DILUTION
When mixing powders of unequal size, the smaller amount powder
is triturated with an equal amount of the larger amount powder.
That mixture is then mixed with an equal amount of the larger
amount powder. The process is repeated until the mixture is
completed.
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reproduced, or re-transmitted without express written permission from the publisher.
OINTMENT SLAB
• An ideal surface for mixing compounds
because of its nonabsorbent surface.
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reproduced, or re-transmitted without express written permission from the publisher.
SPATULAS
• Spatulas
 used to transfer solid ingredients, prepare ointments
and creams, or loosening material from the surfaces
of a mortar and pestle
• Types
 stainless steel
 hard rubber
 plastic
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re-used, reproduced, or re-transmitted without express written permission from the
publisher.
SPATULATION
• Mixing powders using a
spatula
• Can be done in a mortar, on
an ointment slab, or in a
plastic bag.
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without express written permission from the publisher.
LEVIGATION
•Reduces particle size of a powder drug by
triturating it with a solvent in which the drug is
insoluble
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permission from the publisher.
MIXING LARGE QUANTITIES
• Electronic mortar and pestle
 blade assembly inside a plastic mixing jar
 length of time and speed of mixing can be
varied
• Ointment mill
 achieves very uniform particle size in
formulations
 gives smoothness and elegance
SOLUTIONS
• Clear (but not necessarily colorless) liquids
in which the drug is completely dissolved
• The solubility of the drug must be known
before attempting to dissolve it in a
solution.
• Some solids need to be triturated before
mixing into a solution.
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re-used, reproduced, or re-transmitted without express written permission from the
publisher.
SOLUTIONS
• Syrups – concentrated sucrose solution in
water
• Nonaqueous solutions
Elixir
Glycerates
Tincture
Collodions
Spirit
Liniment
Fluid extract
Oleaginous solutions
• Dissolve alcohol soluble ingredients in
alcohol, and water soluble ingredients in
water.
• Add water solution to the alcohol solution.
SUSPENSIONS
• A 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
ADDITIVES
• Flavoring
 The human tongue can distinguish salty, bitter,
sour, and sweet tastes.
• Sweeteners
 Colorless, odorless, solubility in water at the
concentrations needed for sweetening,
pleasant tasting with no “after-taste,” and
stable over a wide pH range
• Coloring
 Not required in every formulation
 Contraindicated in all sterile solutions
 Dark colors may be rejected because they are
often associated with poisons
EMULSIONS
• Unstable system consisting of an oil and
water
 One is dispersed in the form of small
droplets throughout the other.
 Oil-in-water (o/w) emulsion
 Water-in-oil (w/o) emulsion
• Emulsifier
 tragacanth, sodium lauryl sulfate, sodium
dioctyl sulfosuccinate, and polymers
known
as the Spans® and Tweens®
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copied, re-used, reproduced, or re-transmitted without express written permission
from the publisher.
EMULSIONS
• Methods of preparation – requires energy input
• Dry Gum method – primary emulsion
 4:2:1 – gum + oil then water
• Wet Gum method – mucilage
 4:2:1 – gum + water then oil
• Beaker method
 water soluble and oil soluble ingredients heated
in different beakers
 add internal phase to external phase
OINTMENTS
• Used for many different purposes
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protectants
antiseptics
emollients
antipruritics
• Methods to compound ointments
 incorporate drug into ointment base
 create the ointment base as part of compounding
SUPPOSITORIES
• Oleaginous
 primarily synthetic triglycerides
 e.g., FattiBase®, Witepsol®
• Water soluble
 glycerinated gelatin
• dissolve slowly to provide prolonged release of active
ingredients
 polyethylene glycols (PEGs)
• 200, 400, or 600 molecular weight are liquids
• over 1,000 molecular weight are solids
• Hydrophilic
 mixtures of oleaginous and water soluble bases
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re-used, reproduced, or re-transmitted without express written permission from the
publisher.
SUPPOSITORIES
• Ways to compound suppositories
 compression molding
 fusion molding
• Suppository molds
 metal (steel, aluminum)
 plastic
 rubber
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reproduced, or re-transmitted without express written permission from the publisher.
CAPULES
• Hard gelatin capsules consist of a body and a cap which fits
firmly over the body of the capsule.
• 8 sizes available for human use
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May not be copied, re-used, reproduced, or re-transmitted without
express written permission from the publisher.
Sizes
Volume (ml)
000
00
0
1
2
3
4
5
1.37
0.95
0.68
0.50
0.37
0.30
0.20
0.13
PUNCH METHOD*
*used when filling a small number of capsules
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reproduced, or re-transmitted without express written permission from the publisher.
CAPSULES – ADDITIONAL
COMPOUNDING TIPS
• To avoid finger prints on the capsules, use a cap
as a holder, or use finger cots.
• Liquids that do not dissolve gelatin can be
dispensed in capsules.
 fixed oils
• Tablets and smaller capsules can be placed
inside of a capsule.
 reduces the number of single dosage forms
MOLDED TABLETS
• Tablet base is a combination of lactose,
dextrose, sucrose, or mannitol
• Ingredients in base are slightly dissolved with a
wetting solution (alcohol: water)
• Pressed into a tablet triturate mold
 must be calibrated
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May not be copied, re-used, reproduced, or re-transmitted without
express written permission from the publisher.
TABLETS – OTHER COMPOUNDED TABLETS
• Single punch tablet machine
 chewable, effervescent, compressed tablets
• Rapid dissolve tablets (RDT)
 disintegrate or dissolve within minutes on
tongue
 ingredients are very water soluble
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Company. May not be copied, re-used, reproduced, or retransmitted without express written permission from the
publisher.