1. Nonsterile Pharmaceutical Compounding
Chapter 8
Nonsterile Pharmaceutical Compounding
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2. 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.
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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
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4. The Need for Compounding
Sterile compounding
Nonsterile compounding
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Sterile Compounding
Includes preparation of injectable medications
Done mostly in hospital pharmacies
Requires special
Equipment
Workspaces
Expertise
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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
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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
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8. 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.
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9. 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
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10. Nonsterile Compounding
Solution – liquid dosage form
Active ingredient (solute) dissolved in a solution (solvent), which may be water-based or alcohol-based
Suspension – active ingredient not dissolved but dispersed
Has a tendency to settle
Suspending agent prevents settling
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11. Nonsterile Compounding
Regardless of their apparent stability, all suspensions should be dispensed with an auxiliary label reading “Shake Well.”
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12. Nonsterile Compounding
Ointments – water-in-oil emulsions
Occlusive
Greasy
Not water washable
Creams – oil-in-water emulsions
Nonocclusive
Nongreasy
Water washable
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13. 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.
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14. 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
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15. Nonsterile Compounding
Suppositories are prepared by
Melting base material
Adding active ingredient(s)
Pouring into a mold
Chilling to solidify the suppository
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16. 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.
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17. Nonsterile Compounding
Capsule shells consist of a body and cap and are made of
Gelatin
Sugar
Water
Available in standard sizes
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18. Nonsterile Compounding
Commercially available synthetic hormones come in fixed doses for
Hormone replacement therapy (HRT)
Estrogen replacement therapy (ERT)
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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
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20. 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.
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21. 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).
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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
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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.
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24. © Paradigm Publishing, Inc.
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
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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
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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
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USP Chapter 795
Compounded products have beyond-use dating, which is initiated at the time of compounding, not at the time of dispensing.
Product stability must be documented.
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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
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29. © Paradigm Publishing, Inc.
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
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30. © Paradigm Publishing, Inc.
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.
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31. 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.
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32. 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
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33. 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.
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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
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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
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36. © Paradigm Publishing, Inc.
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
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Terms to Remember
prescription record
a computer-generated version of the compounding log that documents the compounding recipe for a specific prescription and patient
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38. © Paradigm Publishing, Inc.
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
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39. 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
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Equipment
Weights and Balances
Pharmaceutical Weights
Forceps and Spatulas
Compounding Slab
Mortar and Pestle
Graduate Cylinders, Pipettes, and Beakers
Other Equipment
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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
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42. © Paradigm Publishing, Inc.
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
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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
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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)
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45. © Paradigm Publishing, Inc.
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
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46. 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
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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.
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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)
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49. © Paradigm Publishing, Inc.
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
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Compounding Slab
Plate is made of ground glass:
Flat, hard, nonabsorbent surface
Used for mixing compounds
Disposable, nonabsorbent parchment paper can be used instead.
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51. © Paradigm Publishing, Inc.
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
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52. 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.
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53. Graduate Cylinders, Pipettes, and Beakers
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54. 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
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55. 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
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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
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Other Equipment
Sterile preparations require additional equipment and space:
Autoclave to sterilize instruments
Incubator to culture products
Clean room environment
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58. 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
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59. 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.
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60. 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.
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61. 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
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62. Technique for Weighing Pharmaceutical Ingredients
Class III prescription balance is sufficient for occasional compounding.
Pharmacist must check all measurements done by technician.
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63. 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
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64. © Paradigm Publishing, Inc.
Terms to Remember
percentage of error
the acceptable range of variation above and below the target measurement; used in compounding and manufacturing
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65. 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.
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66. © Paradigm Publishing, Inc.
Terms to Remember
meniscus
the moon-shaped or concave appearance of a liquid in a graduate cylinder used in measurement
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67. Technique for Measuring Liquid Volumes
Always measure liquids on a solid, level surface at eye level.
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68. 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.
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69. 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
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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
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71. 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.
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72. © Paradigm Publishing, Inc.
Terms to Remember
levigation
a process usually used to reduce the particle size of a solid during the preparation of an ointment
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73. 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.
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74. 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
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75. 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.
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76. 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.
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Terms to Remember
diluent powder mixing
an inactive ingredient that is added to the active drug in compounding a tablet or capsule
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78. 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.
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79. 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.
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Terms to Remember
geometric dilution method
the gradual combining of drugs using a mortar and pestle
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81. 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.
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82. The Compounding Process
Compounding should never be rushed.
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83. The Compounding Process
The pharmacist judges the suitability of the prescription to be compounded in terms of safety and intended use.
The pharmacist retrieves and reviews the master control record in the computer.
(See Table 8.6)
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84. The Compounding Process
The pharmacist prints out a compounding record or log sheet for the technician to make the nonsterile preparation.
A medication container label is typed or created by the computer software using information in the compounding log.
(See Table 8.6)
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85. The Compounding Process
The pharmacist performs all necessary mathematical calculations and identifies the necessary equipment for the technician; the technician double-checks all calculations.
The pharmacy technician uses appropriate protective clothing and handwashing technique.
(See Table 8.6)
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86. The Compounding Process
The technician gathers all necessary active and inactive ingredients, as well as prepares and calibrates any necessary equipment.
The technician weighs and adds all ingredients for the preparation, initials each step, and adds documentation to the compounding record.
(See Table 8.6)
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87. The Compounding Process
The technician labels and stores the medication in a suitable container.
The pharmacist reviews the compounding record and medication container label and assesses the pharmaceutical elegance of the preparation
(See Table 8.6)
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88. The Compounding Process
The technician prepares a medication container label, affixing it to the proper container.
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)
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89. The Compounding Process
The technician cleans all equipment thoroughly and promptly, reshelves all active and inactive ingredients, and properly labels and stores any excess preparation.
The pharmacist counsels the patient at the time of pickup.
(See Table 8.6)
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90. The Compounding Process
Selecting medication containers
Labeling and cleanup
Final check by the pharmacist
Patient counseling by the pharmacist
Reimbursement
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91. 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.
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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.
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93. Final Check by the Pharmacist
Pharmacist is legally responsible for checking the final product:
Master control record
Mathematical calculations
Weight measurements
Container label
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94. Final Check by the Pharmacist
Pharmacist also checks the pharmaceutical elegance of the product:
Adequacy of mixing
Odor
Color
Consistency
pH balance
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95. © Paradigm Publishing, Inc.
Terms to Remember
pharmaceutical elegance
the physical appearance of the final compound preparation
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96. 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
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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.
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