Download Chapter 8 - Denali Rx

Chapter 8
Nonsterile
Pharmaceutical
Compounding
© Paradigm Publishing, Inc.
1
The Need for Compounding
• Before large-scale pharmaceutical
manufacturing, pharmacists compounded
most prescriptions.
• Compounding is still necessary, but most
chain pharmacies do not have the time,
space, or expertise for compounding.
• A growing number of independent
pharmacies are specializing in
compounding service.
© Paradigm Publishing, Inc.
2
Terms to Remember
compounding
the process of preparing a prescribed
medication for an individual patient from
bulk ingredients created by a pharmacist
in order to treat a specified medical
condition according to a prescription by
a licensed prescriber
© Paradigm Publishing, Inc.
3
The Need for Compounding
• Sterile compounding
• Nonsterile compounding
© Paradigm Publishing, Inc.
4
Sterile Compounding
• Includes preparation of injectable
medications
• Done mostly in hospital pharmacies
• Requires special
– Equipment
– Workspaces
– Expertise
© Paradigm Publishing, Inc.
5
Terms to Remember
sterile compounding
the preparation of a parenteral product
in the hospital, home healthcare,
nuclear, or community pharmacy setting;
an example is an intravenous antibiotic
© Paradigm Publishing, Inc.
6
Terms to Remember
nonsterile compounding
the preparation of a medication, in an
appropriate quantity and dosage form,
from several pharmaceutical ingredients
in response to a prescription written by a
physician, such as tablets, capsules,
ointments, or creams; sometimes
referred to as extemporaneous
compounding
© Paradigm Publishing, Inc.
7
Nonsterile Compounding
• There are many examples of nonsterile
compounding preparations:
– Solutions and suspensions
– Ointments and creams
– Suppositories and capsules
• Many dermatologists and gynecologists
prefer to individualize prescriptions for their
patients.
• Pharmacists also compound prescriptions
from dentists and veterinarians.
© Paradigm Publishing, Inc.
8
Nonsterile Compounding
Why compound?
– If prescription calls for a smaller dose
than is commercially available
– If a patient requires alternative dosage
form
• Cannot swallow pills
• Oral medication may harm stomach
• May be allergic to preservatives or colorings
© Paradigm Publishing, Inc.
9
Nonsterile Compounding
• Solution – liquid dosage form
– Active ingredient (solute) dissolved in a
solution (solvent), which may be waterbased or alcohol-based
• Suspension – active ingredient not
dissolved but dispersed
– Has a tendency to settle
– Suspending agent prevents settling
© Paradigm Publishing, Inc.
10
Nonsterile Compounding
Safety Note
Regardless of their apparent
stability, all suspensions should be
dispensed with an auxiliary label
reading “Shake Well.”
© Paradigm Publishing, Inc.
11
Nonsterile Compounding
• Ointments – water-in-oil emulsions
– Occlusive
– Greasy
– Not water washable
• Creams – oil-in-water emulsions
– Nonocclusive
– Nongreasy
– Water washable
© Paradigm Publishing, Inc.
12
Nonsterile Compounding
• Powder is a finely divided admixture
of drugs and/or chemicals.
• Powders range in size from very
coarse (No. 8) to very fine (No. 80).
• Dispensing of medicines in powder
from is very rare.
© Paradigm Publishing, Inc.
13
Nonsterile Compounding
• Suppository – solid dosage form for
insertion into body orifice
– Rectum
– Vagina
– Urethra
• Consists of active ingredient(s) in a base
such as
– Cocoa butter
– Hydrogenated vegetable oil
– Glycerinated gelatin
© Paradigm Publishing, Inc.
14
Nonsterile Compounding
Suppositories are prepared by
– Melting base material
– Adding active
ingredient(s)
– Pouring into a mold
– Chilling to solidify
the suppository
© Paradigm Publishing, Inc.
15
Nonsterile Compounding
• Capsules – solid dosage form with
medicinal preparation inside a gelatin shell
• Medicinal preparation may be
– Powder
– Granules
– Liquid
• Compounding for capsules may be
necessary to provide an unusual dosage
form.
© Paradigm Publishing, Inc.
16
Nonsterile Compounding
• Capsule shells consist of a body and
cap and are made of
– Gelatin
– Sugar
– Water
• Available in standard
sizes
© Paradigm Publishing, Inc.
17
Nonsterile Compounding
Commercially available synthetic
hormones come in fixed doses for
– Hormone replacement therapy (HRT)
– Estrogen replacement therapy (ERT)
© Paradigm Publishing, Inc.
18
Terms to Remember
hormone replacement therapy (HRT)
therapy consisting of some combination
of estrogen, progestin (female), and
androgen (male) hormones
estrogen replacement therapy (ERT)
treatment consisting of some
combination of female hormones
© Paradigm Publishing, Inc.
19
Nonsterile Compounding
• Physician may want to individualize these
hormones instead.
• Bio-identical hormones can be
compounded to meet individual needs.
• Dosing can be based on clinical
observations or lab analysis of serum or
saliva.
• Hormones can be compounded as a gel or
cream formulation.
© Paradigm Publishing, Inc.
20
Laws, Regulations, and
Standards for Compounding
• Compounding pharmacies must be
licensed.
• Federal and state laws and national
standards guide safety practices.
• Compounding pharmacies must
follow good compounding practices
(see Table 8.2).
© Paradigm Publishing, Inc.
21
Terms to Remember
good compounding practices (GCP)
USP standards in many areas of
practice to ensure high-quality
compounded preparations
anticipatory compounding
preparing excess product (besides an
individual compound prescription) in
reasonable quantities; these
preparations must be labeled with lot
numbers
© Paradigm Publishing, Inc.
22
USP Chapter 795
• US Pharmacopeia developed
standards for nonsterile compounding
(Chapter 795):
– Enhances patient safety
– Protects pharmacists from law suits
• FDA elects to use and enforce USP
standards.
© Paradigm Publishing, Inc.
23
Terms to Remember
manufactured products
products prepared off-site by a
manufacturer
compounded preparation
a patient-specific medication prepared
on-site by the technician, under the
direct supervision of the pharmacist,
from individual ingredients
© Paradigm Publishing, Inc.
24
USP Chapter 795
• Contains policies and procedures for
– Quality control, including quality of source
ingredients
– Verification
– Patient counseling
• Quality control also includes
– Training of personnel
– Maintaining stability and consistency of finished
product
– Preventing errors
– Documenting expiration dates
© Paradigm Publishing, Inc.
25
USP Chapter 795
• Material Safety Data Sheet must be
filed for all stored ingredients.
• Contains information on
– Hazards and flammability
– Procedures for treating accidental
ingestion or exposure
© Paradigm Publishing, Inc.
26
USP Chapter 795
• Compounded products have beyonduse dating, which is initiated at the
time of compounding, not at the time
of dispensing.
• Product stability must be
documented.
© Paradigm Publishing, Inc.
27
Terms to Remember
beyond-use dating
the documentation of the date after
which a compounded preparation
expires and should no longer be used
stability
the extent to which a compounded
product retains the same physical and
chemical properties and characteristics it
possessed at the time of preparation
© Paradigm Publishing, Inc.
28
USP Chapter 795
• Chapter 795 provides estimates for
beyond-use dating:
– Refrigerated aqueous solutions = 14 days
– Solids and nonaqueous solutions = 6 months or
less
– All other formulations = 30 days
• When manufactured or bulk materials are
used, take the earlier of these:
– 25% of the remaining expiration date
– 6 months
© Paradigm Publishing, Inc.
29
USP Chapter 795
• Technician should always have
pharmacist check beyond-use dating.
• Beyond-use dating for sterile
preparations is stricter:
– It may be as little as 24 to 72 hours.
– Both stability and sterility must be
documented.
© Paradigm Publishing, Inc.
30
Accreditation of
Compounding Pharmacies
• Many compounding pharmacies seek
national accreditation:
– Protects patients
– Protects businesses from legal challenges
– Differentiates their practices from those of other
pharmacies
• Pharmacy Compounding Accrediting Board
(PCAB) is responsible for accrediting
pharmacies.
© Paradigm Publishing, Inc.
31
Accreditation of
Compounding Pharmacies
• To be accredited, pharmacy must
agree to follow all specified standards
• Must follow continuous quality
improvement (CQI) process, including
– Periodic spot-checks of technicians’
work
– Random selection of product to be
analyzed at an outside lab
© Paradigm Publishing, Inc.
32
The Master Control Record
• The master control record is the
recipe for making the compounded
prescription.
• It is prepared by
the pharmacist
or provided by a
compounding
service.
© Paradigm Publishing, Inc.
33
Terms to Remember
master control record
a recipe for a compound preparation that
lists the name, strength, dosage form,
ingredients and their quantities, mixing
instructions, and beyond-use dating
© Paradigm Publishing, Inc.
34
The Compounding Log
• Generated for each prescription
• Pharmacist uses it to complete the
initial calculations and document them
• Copy of the log
(called the
prescription
record) is filed
and used for
refills
© Paradigm Publishing, Inc.
35
Terms to Remember
compounding log
a printout of the prescription for a
specific patient, including the amounts or
weights of all ingredients and
instructions for compounding; used by
the technician to prepare a compounded
medication for a patient
© Paradigm Publishing, Inc.
36
Terms to Remember
prescription record
a computer-generated version of the
compounding log that documents the
compounding recipe for a specific
prescription and patient
© Paradigm Publishing, Inc.
37
The Compounding Log
Compounding log lists
–
–
–
–
–
–
–
–
–
All ingredients of the compounded preparation
Manufacturer
Wholesaler source
Assigned lot number
NDC number
Expiration date for each ingredient
Quantity made
Date of compounding
Initials of pharmacist and compounding technician
© Paradigm Publishing, Inc.
38
Calculations in the
Compounding Pharmacy
• Technician in a compounding pharmacy
should have
– Knowledge of mathematical conversions
– Aptitude for performing calculations
• Pharmacist is legally responsible for all
calculations made by technicians
• Good practice to double-check
pharmacist’s calculations and those in
the master control record
© Paradigm Publishing, Inc.
39
Equipment
•
•
•
•
•
•
Weights and Balances
Pharmaceutical Weights
Forceps and Spatulas
Compounding Slab
Mortar and Pestle
Graduate Cylinders, Pipettes, and
Beakers
• Other Equipment
© Paradigm Publishing, Inc.
40
Weights and Balances
Technician must become familiar with
weights and balances
Class III prescription balance
• Two-pan balance
• Used to weigh small amounts
(120 g or less)
• Sensitivity requirement around
+/– 6 mg
• Uses pharmaceutical weights to
offset ingredient weight
© Paradigm Publishing, Inc.
41
Weights and Balances
• Counterbalance
– Two-pan balance
– Used for larger weights (up to 5 kg)
– Sensitivity requirement in the range of
+/- 100 mg
– Used for bulk materials, not for
compounding
• Ingredients and weights should be
placed on weighing paper
© Paradigm Publishing, Inc.
42
Terms to Remember
weighing paper
a special paper that is placed on a
weighing balance pan to avoid contact
between pharmaceutical ingredients and
the balance tray; also called powder
paper
© Paradigm Publishing, Inc.
43
Weights and Balances
Digital electronic balance
– Single pan
– Easier to operate than two-pan balance
– More accurate
– Much more
expensive than
two-pan balances
($2,500 or more)
© Paradigm Publishing, Inc.
44
Terms to Remember
digital electronic analytical balance
a single-pan balance that is more
accurate than Class III balances or
counterbalances; has capacity of 100 g
and sensitivity as low as +/–1 mg
© Paradigm Publishing, Inc.
45
Pharmaceutical Weights
• Used with two-pan balances to offset
ingredient weight
• Made of polished brass with noncorrosive
coating
• Set usually
contains both
metric and
apothecary
weights
© Paradigm Publishing, Inc.
46
Forceps and Spatulas
• Forceps are used for grasping small
objects.
• Forceps are used with pharmaceutical
weights to avoid transferring moisture or oil
from hands, which can change weight and
cause measurement errors.
© Paradigm Publishing, Inc.
47
Forceps and Spatulas
• Spatulas are used for various tasks:
– Transferring solid ingredients to weighing pans
– Preparing ointments and creams
– Removing material from mortar and pestle
• Spatulas can be made of
– Stainless steel
– Plastic
– Hard rubber
(useful for
corrosive
materials)
© Paradigm Publishing, Inc.
48
Terms to Remember
forceps
an instrument used to pick up small
objects, such as pharmacy weights
spatula
a stainless steel, plastic, or hard rubber
instrument used for transferring or
mixing solid pharmaceutical ingredients
© Paradigm Publishing, Inc.
49
Compounding Slab
• Plate is made of ground glass:
– Flat, hard, nonabsorbent surface
– Used for mixing compounds
• Disposable,
nonabsorbent
parchment paper
can be used
instead.
© Paradigm Publishing, Inc.
50
Mortar and Pestle
• Used for grinding and mixing ingredients
• Can be made of glass, porcelain, or
Wedgwood
– Coarse-grained porcelain or Wedgwood best
for pulverizing
materials
– Smooth glass sets
best for mixing
liquids and
semisolids
© Paradigm Publishing, Inc.
51
Graduate Cylinders, Pipettes,
and Beakers
• A Graduate cylinder is a flask used for
measuring liquids:
– Can be glass or polypropylene
– Can be conical (wide top, narrow base)
or cylindrical
• Conical graduates are calibrated in both
metric and apothecary units.
• Cylindrical graduates are calibrated in metric
units and are more accurate.
© Paradigm Publishing, Inc.
52
Graduate Cylinders, Pipettes,
and Beakers
© Paradigm Publishing, Inc.
53
Graduate Cylinders, Pipettes,
and Beakers
Beakers are used to measure larger
volumes of liquids:
– Not as accurate as graduate cylinders
– Used when precision is not required
© Paradigm Publishing, Inc.
54
Graduate Cylinders, Pipettes,
and Beakers
A pipette is a long, thin, hollow tube:
– Calibrated
– Used to measure and
transfer liquid volumes
less than 1.5 mL
– Sometimes suction
device used to draw up
liquid
© Paradigm Publishing, Inc.
55
Other Equipment
• Freezers and refrigerators – for storing
ingredients and final products
• Container hood, masks, and gowns – for
protection when working with powders
• Tablet press – for combining tablet
ingredients
• Capsule machine – for making larger
quantities of capsules
© Paradigm Publishing, Inc.
56
Other Equipment
Sterile preparations require additional
equipment and space:
– Autoclave to sterilize instruments
– Incubator to culture products
– Clean room environment
© Paradigm Publishing, Inc.
57
Attire and Preparation
Requirements
• Minimum requirements for nonsterile
compounding
– Hairnet
– Long lab coat
– Gloves
• And for hazardous chemicals
–
–
–
–
Eye goggles
Mask
Double gowning
Eyewash station
© Paradigm Publishing, Inc.
58
Attire and Preparation
Requirements
USP Chapter 795 also specifies the
following:
– All personnel must wash hands before
and after each compounding procedure.
– Disposable gloves must be discarded
after each procedure.
– No food items should be stored or
consumed in the staging area.
© Paradigm Publishing, Inc.
59
Technique for Weighing
Pharmaceutical Ingredients
• Accurately weighing ingredients is
one of the most important parts of
compounding.
• The electronic balance is the
preferred piece of equipment.
© Paradigm Publishing, Inc.
60
Technique for Weighing
Pharmaceutical Ingredients
• Must be perfectly level (front to back
and side to side)
• Should be warmed up and calibrated
each day prior to use
• Should be locked when not in use
• Must be cleaned after each use
© Paradigm Publishing, Inc.
61
Technique for Weighing
Pharmaceutical Ingredients
• Class III prescription balance is
sufficient for occasional
compounding.
• Pharmacist must check all
measurements done by technician.
© Paradigm Publishing, Inc.
62
Calculating Percentage
of Error
• Error in measurement is expected in
nonsterile compounding.
• Allowances are made for a certain
percentage of error.
• Most balances are marked with their
degree of accuracy.
• Percentage of error is calculated as
(amount of error / quantity desired) x 100
© Paradigm Publishing, Inc.
63
Terms to Remember
percentage of error
the acceptable range of variation above
and below the target measurement;
used in compounding and
manufacturing
© Paradigm Publishing, Inc.
64
Technique for Measuring
Liquid Volumes
• Always select the measuring device
that yields the most accurate volume.
• Use the smallest device that holds the
required volume.
• Measure the liquid at eye level.
• Read the level at the bottom of the
meniscus.
© Paradigm Publishing, Inc.
65
Terms to Remember
meniscus
the moon-shaped or concave
appearance of a liquid in a graduate
cylinder used in measurement
© Paradigm Publishing, Inc.
66
Technique for Measuring
Liquid Volumes
Safety Note
Always
measure
liquids on a
solid, level
surface at eye
level.
© Paradigm Publishing, Inc.
67
Techniques for Mixing
Compounded Drugs
• Technician should first gather these items:
–
–
–
–
Master control record
Ingredients
Equipment
Mixing directions
• Adequate and uninterrupted time must be
provided.
• Best mixing technique should be retrieved
from the master control record or from the
pharmacist.
© Paradigm Publishing, Inc.
68
Techniques for Mixing
Compounded Drugs
• Comminution is the act of reducing a
substance to small, fine particles.
• Blending is the act of combining two
substances.
• Trituration involves rubbing or grinding a
substance to create fine particles:
– Generally done with mortar and pestle
– Rapid motion with minimal pressure produces
best results
© Paradigm Publishing, Inc.
69
Terms to Remember
comminution
the act of reducing a substance to small,
fine particles, including trituration,
levigation, pulverization, spatulation,
sifting, and tumbling
blending
the act of combining two substances
© Paradigm Publishing, Inc.
70
Techniques for Mixing
Compounded Drugs
• Levigation is used when reducing
particle size for use in ointments.
• A paste is formed with the solid and a
levigating agent:
– Castor oil
– Mineral oil
• The paste is then triturated with a
mortar and pestle.
© Paradigm Publishing, Inc.
71
Terms to Remember
levigation
a process usually used to reduce the
particle size of a solid during the
preparation of an ointment
© Paradigm Publishing, Inc.
72
Techniques for Mixing
Compounded Drugs
• Pulverization by intervention reduces
particle size with the use of a volatile
solvent:
– Camphor
– Alcohol
– Iodine
– Ether
• The solvent is then permitted to
evaporate.
© Paradigm Publishing, Inc.
73
Techniques for Mixing
Compounded Drugs
• Spatulation uses a spatula to combine
and mix
• Sifting is used to blend powders
• Tumbling involves placing powders
into a container and shaking
© Paradigm Publishing, Inc.
74
Techniques for Mixing
Compounded Drugs
• Most ointments and creams are
prepared with manual incorporation of
materials.
• In some cases, dry ingredients must
be triturated to avoid a gritty
appearance.
© Paradigm Publishing, Inc.
75
Techniques for Mixing
Compounded Drugs
• Powders can be combined using one
of the following techniques:
– Spatulation
– Trituration
– Sifting
– Tumbling
– Levigation
• A diluent powder may be necessary
for pediatric doses.
© Paradigm Publishing, Inc.
76
Terms to Remember
diluent powder mixing
an inactive ingredient that is added to
the active drug in compounding a tablet
or capsule
© Paradigm Publishing, Inc.
77
Techniques for Compounded
Drugs
• Hand-filling capsules
can be done with
the punch method.
• The body of the capsule
is punched into a cake
of powder until it is full.
© Paradigm Publishing, Inc.
78
Techniques for Mixing
Compounded Drugs
• Mortar and pestle can be used to mix
more than one drug.
• Geometric dilution method begins by
adding the most potent drug.
• An equal amount of the next most
potent drug is added and mixed.
• Each successive addition should
equal the amount in the mortar.
© Paradigm Publishing, Inc.
79
Terms to Remember
geometric dilution method
the gradual combining of drugs using a
mortar and pestle
© Paradigm Publishing, Inc.
80
The Compounding Process
• USP Chapter 795 lists fourteen steps
for compounding a nonsterile
preparation.
• These steps, or something similar,
should be included in the pharmacy’s
procedure manual.
© Paradigm Publishing, Inc.
81
The Compounding
Process
Safety Note
Compounding should never be
rushed.
© Paradigm Publishing, Inc.
82
The Compounding Process
1. The pharmacist judges the suitability of
the prescription to be compounded in
terms of safety and intended use.
2. The pharmacist retrieves and reviews the
master control record in the computer.
(See Table 8.6)
© Paradigm Publishing, Inc.
83
The Compounding Process
3. The pharmacist prints out a compounding
record or log sheet for the technician to
make the nonsterile preparation.
4. A medication container label is typed or
created by the computer software using
information in the compounding log.
(See Table 8.6)
© Paradigm Publishing, Inc.
84
The Compounding Process
5. The pharmacist performs all necessary
mathematical calculations and identifies
the necessary equipment for the
technician; the technician double-checks
all calculations.
6. The pharmacy technician uses
appropriate protective clothing and
handwashing technique.
(See Table 8.6)
© Paradigm Publishing, Inc.
85
The Compounding Process
7. The technician gathers all necessary
active and inactive ingredients, as well as
prepares and calibrates any necessary
equipment.
8. The technician weighs and adds all
ingredients for the preparation, initials
each step, and adds documentation to
the compounding record.
(See Table 8.6)
© Paradigm Publishing, Inc.
86
The Compounding Process
9. The technician labels and stores the
medication in a suitable container.
10. The pharmacist reviews the compounding
record and medication container label
and assesses the pharmaceutical
elegance of the preparation
(See Table 8.6)
© Paradigm Publishing, Inc.
87
The Compounding Process
11. The technician prepares a medication
container label, affixing it to the proper
container.
12. The pharmacist signs and dates the
compounding record and/or prescription,
files the records, and places the
compounded preparation in a storage bin
for patient pickup.
(See Table 8.6)
© Paradigm Publishing, Inc.
88
The Compounding Process
13. The technician cleans all equipment
thoroughly and promptly, reshelves all
active and inactive ingredients, and
properly labels and stores any excess
preparation.
14. The pharmacist counsels the patient at
the time of pickup.
(See Table 8.6)
© Paradigm Publishing, Inc.
89
The Compounding Process
•
•
•
•
•
Selecting medication containers
Labeling and cleanup
Final check by the pharmacist
Patient counseling by the pharmacist
Reimbursement
© Paradigm Publishing, Inc.
90
Selecting Medication
Containers
• Technician should choose the best
container for the specific drug dispensed.
– Amber-colored vials protect product from
light.
– Oral syringes are calibrated for
dispensing creams and gels.
– New TopiClick container dispenses a
measured amount of medication.
© Paradigm Publishing, Inc.
91
Labeling and Cleanup
After compounding
– Prescription must be labeled with all required
information.
– Prescription balance should be locked and
covered.
– Equipment and work area should be thoroughly
cleaned.
– Ingredients should be properly stored.
– Expired or discarded product should be sealed
and placed in a biohazard container.
© Paradigm Publishing, Inc.
92
Final Check
by the Pharmacist
Pharmacist is legally responsible for
checking the final product:
– Master control record
– Mathematical calculations
– Weight measurements
– Container label
© Paradigm Publishing, Inc.
93
Final Check
by the Pharmacist
Pharmacist also checks the
pharmaceutical elegance of the
product:
– Adequacy of mixing
– Odor
– Color
– Consistency
– pH balance
© Paradigm Publishing, Inc.
94
Terms to Remember
pharmaceutical elegance
the physical appearance of the final
compound preparation
© Paradigm Publishing, Inc.
95
Patient Counseling
by the Pharmacist
• Pharmacist must offer counseling to all
patients regarding compounded
preparations.
• Pharmacist should ensure that the
patient knows
– How to take the medication
– How to properly store the medication
– The beyond-use or expiration date of the
medication
© Paradigm Publishing, Inc.
96
Reimbursement
• Insurance generally does not cover
compounded preparations.
• The cost to the patient is based on
time and experience of staff, not on
the cost of the ingredients.
• Some insurance companies will
accept a Universal Claim Form from
the pharmacy and reimburse the
patient later.
© Paradigm Publishing, Inc.
97