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previously published work.
Review PHARMACY PRACTICE

Extemporaneous Compounding: Selective Pharmacists with Separate Skill

AK Mohiuddin, Assistant Professor
Department of Pharmacy, World University of Bangladesh, Bangladesh

Abstract
Extemporaneous compounding takes place in community and hospital pharmacies. There are usually specialist compounding
pharmacies in major towns and cities, but any pharmacy may undertake compounding as long as they have appropriate facilities
according to state-based legislation (e.g. allocated clean bench, specific compounding equipment). Although development is a
continuous process, companies are customizing features to meet the majority of patient needs, but the very nature of the process
cannot meet all patient needs. The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require
specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However,
if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no
commensurate benefit. Published reports of independent testing by the FDA, state agencies, and others consistently show that

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compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs. Compounded sterile preparations
pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been
traced to purportedly ‘sterile’ steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies.

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The 2012 outbreak has resulted in intense scrutiny of pharmacy compounding practices and increased recognition of the need to ensure
that compounding is limited to appropriate circumstances.

Keywords: Pharmacy Practice; Drugs; Dosage Forms; Compounding; Equipment; Pharmacopeia

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Purpose of the Study
The article aims to physico-chemical and economic
considerations before compounding; factors and quality
control issues; compounding support, training, chemical
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supplies, types of compounding (especially in hospital and

ambulatory care compounding). It should aid to practice the
extemporaneous preparation of basic and advanced
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formulations including pharmacopoeial and non-

pharmacopoeial formulations encountered in pharmacy Figure 1. Graphical Abstract
practice, together with requisite documentation, labeling,
packaging and counseling requirements. Along with this, they Article Highlights:
have to study the analysis of formulations and their 1. An estimate by FDA that 1-10% of all prescriptions require
components and relate these to the clinical performance of compounding was not supported by evidence data.
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medicines. This will help them to investigate, evaluate and 2. In 2006, the FDA conducted a limited survey of
report the physical characteristics of formulations including compounded drugs revealed failure rate of 33%.
release kinetics and relate these to quality control and 3. In 2001, a Kansas City-based pharmacist was discovered
preformulation requirements; relate the application of quality to have adulterated 72 different drugs, including many
control, quality assurance and the principles of good oncology medications, to increase profits.
manufacturing practice to regulation of medicine production in 4. Over the period 2008–2010, the Texas State Board of
home and abroad. Pharmacy found an overall potency failure rate of 23% for
compounded drugs
5. Methylprednisolone injections from a single compounding
pharmacy in the USA resulted in 137 cases of Aspergillus
fumigatus meningitis and 12 deaths.
6. Even where a given formulation has been shown to
Corresponding author: AK Mohiuddin, Assistant Professor
achieve suitable physical, chemical and microbiological
Department of Pharmacy, World University of Bangladesh
stability, the bioavailability and palatability of the
151/8, Green Road, Dhanmondi, Dhaka – 1205, Bangladesh
preparation may be unproven.
Phone: +8801716477485; Email: [email protected]

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Review PHARMACY PRACTICE

7. Ingredients, intended use, dosage, and method of to meet the needs of their own community of patients. Most
administration, education, skill and expertise; proper compounding pharmacists appear to be interested and excited
equipment, supplies, chemicals the guidelines delineated about their practices. In fact, many pharmacists intimately
in US pharmacopeia, necessary calculations and involved in pharmaceutical care have now realized the
documentation; expected duration of therapy, physico- importance of providing individualized patient care through the
chemical compatibility are the major considerations preparation of patient-specific products. Compounding
before compounding. pharmacy is not for everyone, but as it grows, it will provide an
8. Quality must be built-in to the preparation from the increasingly significant number of pharmacists the excitement
beginning steps to evaluating the final preparation. and fulfillment of using their innovative and creative skills to
9. The use of an alternative route of administration (use of solve patient problems. All components of a compounded
the rectal rather than the oral route) could also be product, that is the active ingredient and the excipients, are
considered if an appropriate formulation is available. subject to quality standards set out in the Therapeutic Goods
Act 1989, and are sourced from compounding supply
Introduction companies that undertake rigorous quality-assurance testing.
The FDA defines traditional pharmacy compounding as the
combining, mixing, or altering of ingredients to create a
customized medication for an individual patient in response

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to a licensed practitioner’s prescription. The NABP
further describes compounding as the result of a practitioner’s
prescription drug order based on the

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practitioner/patient/pharmacist relationship in the course of
professional practice. Traditional pharmacy compounding plays
a valuable role in providing access to medications for
individuals with unique medical needs, which cannot be met
with a commercially available product. For instance, a
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prescriber may request that a pharmacist compound a
suspension for a pediatric or geriatric patient unable to swallow
a medication in its commercially available form. In traditional
pharmacy compounding, an individualized medicine is
prepared at the request of a prescriber on a small scale. It is
obvious that large scale manufacturers have very limited
opportunity to customize dosage strength and dosage forms for
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a customer segment that is not substantially big enough due to

economies of scale concept of business. Another major
difference is that compounding pharmacies are not required to
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Figure 2. Rationale of Extemporaneous compounding

report adverse events to the FDA, whereas adverse event (Source: Velpandian T., Das U.S. (2016) Extemporaneously
reporting is mandatory for manufacturers of FDA-regulated Used Drug Formulations for Ocular Emergencies.
medications. Thus, adverse events associated with In: Velpandian T. (eds) Pharmacology of Ocular
compounded drugs may be difficult to detect, particularly if the Therapeutics. Adis, Cham
affected patients are widely scattered in different geographic
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areas. Registered and skilled pharmacists in practicing their art Rationale of Extemporaneous Compounding
of compounding fills in this gap to meet individualized needs. An estimate by FDA that 1-10% of all prescriptions require
Compounding has always been a basic part of pharmacy compounding was not supported by evidence data. EP
practice; the drugs, dosage forms, and equipment or strategies in clinical studies requires 'fit-for-purpose'
techniques used are the variables. Pharmacists have unique formulation design and preparation processes, as well as
knowledge and skills and are not duplicated by any other administration procedures that are safe, flexible, cost-effective,
profession. Pharmacy activities to individualize patient therapy and simple to adapt by a compounding pharmacist at the
include compounding and clinical functions. Either function in clinical site. Many commercially available medications are not
the absence of the other results in placing pharmacy in a manufactured in suitable dosage forms for these special
vulnerable position. It is important to entrust a pharmacist’s populations, e.g., liquid formulations for children and those
expertise to adjust dosage quantities, frequencies, and even who may be unable to swallow tablets. Additionally, when drug
dosage forms to enhance compliance. Pharmacy is a complex shortages occur or for the treatment of rare diseases,
mixture of different practices and practice sites. No longer is compounded products have a place in practice. Examples of
pharmacy simply community pharmacy or hospital pharmacy. altered drug products include topical ointments, eye drops,
Pharmacy is diverse and offers many opportunities for those solid or liquid oral dosage forms, and intravenous infusions.
willing to look around, find their niche and practice pharmacy Compounding also has a place in veterinary practice, where

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medicines may be altered to suit drug absorption, metabolism,  If a particular medicine is not available as a liquid
and swallowing abilities of different species. The use of small- formulation, another medicine from the same
scale compounded medications carries certain risks, as they are therapeutic classification may well be used, such as
not assessed for product quality, stability, or efficacy. The the use of a less potent steroid rather than diluting a
importance of a collaborative, team-based approach to patient potent one.
care and safety has been well established within the health  Using a suitable preparation intended for a different
field. The requirement for alternative medications and dosage route of administration, for example, using an
forms may be determined by the patient’s general practitioner injectable solution orally.
who prescribes the medication or other allied health  Use of a ‘specials’ preparation manufactured in
professionals: a speech pathologist who identifies a swallowing licensed premises (Specials are medicines made in
difficulty, a physiotherapist applying ultrasound, which may larger volumes by a licensed manufacturer) [7].
interfere with transdermal drug delivery, or an occupational
therapist identifying that a patient is unable to physically Considerations before compounding
manipulate their current medication or its packaging. This  Commercially availability of drug in dosage form,
highlights the importance for other members of the health care strength, and packaging
teams to have knowledge and understanding of compounded  Ingredients, intended use, dosage, and method of
medications. Among elderly patients, the incidence of administration concern

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dysphagia is reportedly as high as 7%–13%, making utilization  Education, skill and expertise to drug compounding
of available oral dosage formulations unfeasible or unsafe.  Proper equipment, supplies, chemicals and the
Similarly, Canadian hospital pharmacists often encounter guidelines delineated in us pharmacopeia

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patients with oral, neck, or gastric cancer, which may make  An alternative by which the patient will receive a
commercial solid dosage formulations impossible to use. Based benefit
on pharmacists’ perspective, using more extemporaneous  Safety of the compounded product
prepared products could also make sense economically. ‘The  Patient necessary storage facility, if required,
significant therapeutic improvement and some cost savings  Necessary calculations to prepare the product
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may be gained’ by the rational use of extemporaneously  Necessary documentation to complete preparation
prepared medicines. Pharmacists that did not provide  Literature reference that might provide information
compounding service cited by the main reason as not receiving on use, preparation, stability, administration
prescriptions that required compounding (63.6% of non-  Expected duration of therapy
compounder pharmacists). In about 33% of the compounded  Some basic quality control to check the product prior
products, they indicated patient-specific reasons. In about 10% to dispensing (e.g., capsule weight variation, pH, visual
this reason concerned a strictly defined pharmaceutical care observations)
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issues. Some researchers conclusively said that 73.2%  Ingredient identity, quality, and purity
pharmacists reported their goal in providing full pharmaceutical  Corrective methods
care to their patients was the most important motivator. The  Physico-chemical incompatibilities [5,6]
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main reasons for the decision to provide compounding service

were want to provide full pharmaceutical care to patients Economic Considerations: The most significant factor which
(73.8% of compounder pharmacist) and responding to requests limits prescribing of compounded medicines was that patients
by prescribers. Most community pharmacists (nearly 70%) did not want products due to these products were not covered
accepted compounding as a component of pharmaceutical by the national insurance. Furthermore, for doctors not
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care. In most of the studies, major reasons stated by physicians prescribing these products, the major barrier to prescribing was
for prescribing extemporaneous products were that they their lack of knowledge of the products. Most responding
worked well for certain conditions and that the product was not doctors do not prescribe medications that require
available commercially [1-7]. compounding because they lack trust in the quality of the
compounded formulations. However, most of the doctors
Evaluation of the Need expressed a desire to learn more as shown in having access to
 Soluble or dispersible tablets may be a useful and information about the usefulness of extemporaneous products.
convenient alternative to the preparation of liquid There are at least two different economic considerations in
extemporaneous products. Some tablets can be making the decision to compound prescriptions; these include
dispersed or crushed and information on this aspect (a) pharmacist compensation and (b) health-care costs. The
can be obtained from the Medicines Information pricing of a compounded prescription should include
Section within the healthcare setting. In this case, the consideration for pharmacodynamic and pharmacotherapeutic
dose should be prepared and administered decision making, formulation expertise, time, and
immediately. In general, compressed tablets or tablets reimbursement of materials. Compounding prescriptions can
which are scored or just film coated can be crushed be attractive professionally and financially. Compounding
whereas modified release tablets cannot. prescriptions can be a way of lowering the cost of drug therapy.

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In some cases, it is less expensive for the pharmacist to prepare manufactured drug product is the source of active ingredient)
a specific prescription for the patient, which may mean the — The beyond-use date is not later than 25% of the time
difference between the patient actually obtaining the drug or remaining until the product’s expiration date or 6 months,
doing without it. If compounding a prescription results in a whichever is earlier. A USP or NF substance is the source of
patient being able to afford the drug therapy, it must be active ingredient— The beyond-use date is not later than 6
considered. An interesting example involves the drug 4- months. For water-containing formulations (prepared from
aminopyridine. Although physicians had been prescribing ingredients in solid form)—The beyond-use date is not later
unapproved versions of the drug for up to 20 years, it was not than 14 days when stored at cold temperatures. For all other
until the drug was studied systematically that rare seizures formulations—The beyond-use date is not later than the
were discovered as a potential side effect. In this case, the intended duration of therapy or 30 days, whichever is earlier.
medical profession pushed for an approved version to be These beyond-use date limits may be exceeded when there is
marketed, rationalizing that if a seizure occurred in the context supporting valid scientific stability information that is directly
of a patient taking an FDA-approved alternative [4-10]. applicable to the specific preparation (i.e., the same drug
concentration range, pH, excipients, vehicle, water content).
Compounding Factors For example, active ingredients containing an ester functional
Stability: One key factor in compounding prescriptions is group, such as aspirin and penicillins, are susceptible to
stability. The more common types of stability of which breakdown by hydrolysis, while those containing aldehyde or

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compounding pharmacists should be aware include chemical, hydroxyl groups, such as testosterone and dopamine, undergo
physical, and microbiological. Whereas commercially oxidative decomposition. A 10°C increase in temperature can
manufactured products are required to possess an expiration result in a 2–5-fold faster rate of degradation. The instability of

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date, compounded products are assigned a beyond-use date. dapsone suspensions prepared in Oral Mix and stored at 25°C
There are numerous sources of information that can be used may be explained by a Maillard reaction between the sucrose
for determining an appropriate beyond-use date, such as in the vehicle and the amino groups of the dapsone. The results
chemical companies, manufacturers literature, laboratory data, of this study have demonstrated the stability, for up to 90 days,
journals, and published books on the subject. Generally, most of dapsone suspensions (2 mg/mL) prepared from commercial
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pharmacists prepare or dispense small quantities of tablets in Oral Mix SF and stored at 5°C and 25°C or prepared in
compounded products; recommend storage at room, cool, or Oral Mix and stored at 5°C, in amber plastic bottles and amber
cold temperatures; and use a conservative beyond-use date. plastic syringes. These suspensions should be shaken before
For nonaqueous liquids and solid formulations (for which the use [2],[5],[6], [11], [12].
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Exhibit 1. Common degradation pathways of active drugs in compounded products* [2,5]

Pathway Factors determining Susceptible functional Examples
degradation rate groups
Oxidation Concentration of Aldehydes, alcohols, Paracetamol, progesterone, testosterone, quinine,
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drug, temperature, phenols, alkaloids, oils (unsaturated fats) such as soybean and corn oil,
catalysts, solvents, unsaturated alkyl chains, essential fats, atorvastatin, atenolol
light and excipients carboxylic acids
(O2 dependent) Esters, amides, lactones, Aspirin, vigabatrin, norfloxacin, omeprazole,
ethers, lactams, imines, simvastatin (statins), baclofen, diphenoxylate,
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acetals, anhydrates, methylphenidate, lignocaine, sildenafil, penicillins,

sulfonamides cephalosporins, diazepam, digoxin, heparin, captopril,
hydrocortisone
*Drug molecules with more than one functional group can be more easily degraded. In fact, many drugs contain more than one
functional group, being susceptible to both oxidation and hydrolysis, e.g. atenolol (contains amide and alcohol groups)

It is essential that the active ingredient does not interact with compounded medicine degrading, short-term expiry dates are
any excipients originating from the dosage form being crushed used (e.g. 28 days for oral and topical products, or 24 hours for
for reformulation (e.g. tablet lubricants and fillers), or from parenteral formulations), unless stability studies have been
additives in the new formulation (antioxidants, preservatives, conducted and indicate otherwise [2,5].
suspending agents, colourants, emulsifiers). Interactions with
other ingredients can result in physical instability of the Potential Risks: FDA-approved drugs are made and tested in
product, such as precipitation of the active drug or phase accordance with GMPs, which are federal statutes that govern
separation (‘cracking’) of a cream, affecting drug solubility, the production and testing of pharmaceutical products. In
absorption and bioavailability. To minimize the risk of a contrast, compounded drugs are exempt from GMPs, and

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testing to assess product quality is inconsistent. Unlike When compounding is performed on a large scale, such errors
FDA-approved drugs, pharmacy-compounded products are not may adversely affect many patients. Published reports of
clinically evaluated for safety or efficacy. The NABP independent testing by the FDA, state agencies, and others
further describes compounding as the result of a consistently show that compounded drugs fail to meet
practitioner’s prescription drug order based on the specifications at a considerably higher rate than FDA-approved
practitioner/patient/pharmacist relationship in the course of drugs. Compounded sterile preparations pose the additional
professional practice. In addition, compounded preparations risk of microbial contamination to patients. In the last 11 years,
do not have standard product labeling or prescribing three separate meningitis outbreaks have been traced to
information with instructions for safe use. Compounding purportedly ‘sterile’ steroid injections contaminated with
pharmacies are not required to report adverse events to the fungus or bacteria, which were made by compounding
FDA, which is mandatory for manufacturers of FDA-regulated pharmacies. US-FDA and the NICHD, have worked together to
medications. Some pharmacies engage in activities that extend develop product labeling for pediatric patients for existing and
beyond the boundaries of traditional pharmacy compounding, new drug molecules coming to the market, if the drug has been
such as large-scale production of compounded medications or could be used in children. When compared to GMPs, the
without individual patient prescriptions, compounding drugs manufacturing standards required by FDA for commercial
that have not been approved for use in the US, and creating products, there are multiple recognized deficiencies inherent in
copies of FDA-approved drugs. Compounding drugs in the extemporaneous formulation-compounding suitable for

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absence of GMPs increases the potential for preparation errors. pediatric patients [11, 13].

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Exhibit 2. Why Is Off-Label Use of Drugs in Children Still a Problem? [13]
 Lack of specifications required for component development by compounding pharmacies.
 No onsite testing of active ingredients and excipients for purity, potency, content and stability.
 No onsite specifications or testing of product containers and closures.
 Site-to-site variations in compounding procedures, equipment, and the degree of product
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handling/manipulation.
 Lack of environmental control, which might lead to unintentional contamination and generation of degradation
products due to inconsistent exposure to light, temperature and processing controls.
 Lack of testing of finished products for purity, potency, content or stability.
 Stability data for establishing expiry dates of compounded products are derived from published data, where
preparation methods likely vary from local methods, or are simply default expiry periods defined by regional
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pharmacy regulations and “best practices”.

 Published preparation methods provide only a portion of the information needed to consistently prepare a
stable potent final product.
Limited options available to mask bad-tasting active ingredients.
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
 The dose administration technologies used such as droppers, syringes, scoops, spoons, etc., vary between sites
and between prescription fills.
 Weak regulatory oversight.
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Quality Control: One of the fastest growing and most important methods should be implemented to ensure that the
areas of pharmaceutical compounding is that of quality control. appropriate quality is achieved, in accordance with the risk
Quality must be built-in to the preparation from the beginning assessment carried out. At a minimum, the starting materials
steps to evaluating the final preparation. The extent of quality and finished product should be examined visually before supply
control applied to a product should be proportionate with the to a patient. There are several quality control tests that can be
level of risk the finished product could pose to the patient and done within the pharmacy and others can be sent to a contract
should be judged on a case by case basis. Even where a given laboratory. The following quality control tests can be
formulation has been shown to achieve suitable physical, considered for the respective dosage forms.
chemical and microbiological stability, the bioavailability and
palatability of the preparation may be unproven. Consideration  Oral and topical liquids (solutions, suspensions,
should be given to the individual patient’s age and condition, emulsions): Weight/volume, pH, specific gravity, active
whether the product will be ingested or used topically, as well drug assay, globule size range, rheological
as the potency of, and risk posed by, the active substances properties/pourability, physical observation (color, clarity),
and/or excipients. Where it is not practical to carry out this physical stability (discoloration, foreign materials, gas
testing (e.g. due to the batch size, urgency, etc.), other suitable formation, mold growth).

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 Hard Gelatin Capsules: Weight-overall average weight, Training and Experience: Pharmacists involved in upgrading
weight individual weight variation, dissolution of capsule and increasing the traditional aspects of extemporaneous
shell, disintegration and/or dissolution of capsule contents, compounding need to keep current with all the new tools of
active-drug assay, physical appearance (color, uniformity, their trade, retrieve the old from storage, and put in a bit of
extent of fill, locked), physical stability (discoloration, practice using their scientific background and their art before
changes in appearance). they will be comfortable in exhibiting their skills. The
 Ointments, Creams and Gels: Theoretical weight pharmacist must ensure that the staff, facilities and systems in
compared to actual weight, pH, specific gravity, active drug place are capable on a day-to-day basis of providing an
assay, physical observations (color, clarity, texture-surface, adequate quality service able to meet the needs of patients.
texture-spatula spread, appearance, feel) and rheological There should be an adequate number of competent personnel
properties. at all times. All staff involved in extemporaneous preparation
 Suppositories, Troches, Lollipops and Sticks: Weight, must receive training Appropriate to their role. Typically, this
specific gravity, active drug assay, physical observation will: (a) provide them with knowledge in good extemporaneous
(color, clarity, texture of surface, appearance, feel), preparation practice, local practices including health and
melting test, dissolution test, physical stability. safety, formulation, expiry periods and quality assurance
 Parenteral preparations: Weight/volume, physical appropriate to the level of involvement, assessment of risk and
observation, pH, specific gravity, osmolality, assay, color, medication error potential, the pharmacy, its products and

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clarity, particulate matter, sterility, pyrogenicity [5,6], [14]. services provided (b) demonstrate competency in the
necessary extemporaneous preparation skills and
Compounding Support: Numerous agencies, companies, pharmaceutical calculations and dilutions. During training, staff

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organizations, etc., are available to assist pharmacists in must be carefully supervised and checked and trainees must
compounding. Information, chemicals, supplies, and understand the limits of their responsibilities. When
equipment are readily available. Chemical and supply considering providing additional services of compounding in an
companies have increased in size and number in recent years institution, pharmacists should not expect that this will change
and many provide information on compounding, a great deal of their practice in time consumed for
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incompatibilities, and stability. Specialty compounding compounding. A written training program should be available
organizations have developed over recent years and generally and completion of training should be documented. This applies
provide full-line services and products to the compounding to all personnel working in the preparation area, including
pharmacist. Many national organizations provide continuing those not directly involved in preparation processes (e.g.
professional education programs in both non-sterile and sterile cleaning staff). [14].
compounding. These entities provide services to compounding
pharmacists ranging from selling only compounding aids to Equipment: The equipment needed will be determined by the
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providing only chemicals. Others offer additional services to type and extent of the services one chooses to provide. Many
include formulas as well as consulting expertise by telephone pharmacies already have clean air environments (e.g., laminar
or via the internet. This service can assist in the process of air flow hoods, isolation barrier systems) where aseptic
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compounding a particular product that may be difficult. compounding of sterile solutions is performed. These same
units can be used to compound other sterile preparations such
as eye drops. A balance, preferably electronic, is essential.
Ointment slabs (i.e., pill tiles), along with spatulas of different
Exhibit 3. MHRA (2007) types and materials, should be purchased. A few mortars and
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in the context of extemporaneous preparation [14] pestles (i.e., glass, ceramic, plastic) and some glassware should
 Extemporaneously prepared medicines should be be secured. A policy for the segregation of specific equipment
formulated and prepared in compliance with current for certain product types, including cytotoxic drugs and external
legal requirements and standards. products, should be available; this should take into account
 Preparation and quality control arrangements are to be local COSHH assessments. Equipment should be calibrated and
documented and in compliance with current GPP validated to demonstrate satisfactory performance. Measures
requirements. should be calibrated for specific volumes and should have
 All products prepared should be quality suitable for levelling lines. Glassware should be inspected regularly, before
their intended use and after each use, for chips and cracks, and replaced as
 Products are released for patient use only by a necessary. Consideration should be given to the merits of other
pharmacist. materials. Stainless steel of a suitable grade is a good material
 Documentation and records should comply but care must be taken with some agents as it is susceptible to
recommendations in this guidance document. oxidation. Plastics are susceptible to surface scratches and
stains. The accuracy of balances should be checked on a regular
basis and records of this process maintained. It may not be
necessary to buy a roomful of equipment, but one should

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purchase what is needed to start the service and should build splashes. Washing and cleaning activities should not
on it as the service grows and expands to different arenas. themselves be a source of contamination. All equipment should
Much of the equipment used today in compounding has be visibly clean prior to use. Ensure that all residues of cleaning
changed. Today, electronic balances are used more often than agent have been removed Containers and lids should be
torsion balances; micro-pipets are commonplace; and ultra- checked to ensure that they are clean and dry before use.
freezers are sometimes required in addition to standard Adequate pest control measures should be taken. [6], [10], [19]
refrigerator freezers. This area is constantly changing and the
compounding pharmacist should be aware of the available Formulas: Consistency of the compounded product is
technology to prepare accurate and effective prescriptions. important. Formulas should be developed or obtained and tried
Becoming acquainted with the local representative for a to assure that each time an extemporaneous product is
laboratory supply company is helpful [2], [6], [14-19]. prepared, the methods used, ingredients added, and the order
of steps is documented. This accomplishes three things. First, it
Environment: A separate area for traditional compounding is provides the methodology for each person involved or
recommended, rather than simply cleaning off a small area of requested to provide such service the information necessary to
the dispensing counter. The compounding pharmacist needs a do so properly. Second, it provides consistency from batch to
clean, neat, well-lit and quiet working area. If aseptic batch. Third, if the product does not turn out the way expected,
compounding is considered, a clean air environment (e.g., a stepwise methodology exists for reviewing and determining

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laminar air flow hood, isolation barrier system) should be used. what happened and if revisions and improvements are needed
The actual facility to be used depends on the level and volume [6], [15].
of compounding to be done. Extemporaneous compounding

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takes place in community and hospital pharmacies. There are Chemicals and Supplies: If one is going to prepare a topical
usually specialist compounding pharmacies in major towns and product, a vehicle (e.g., cream, ointment, gel) and the active
cities, but any pharmacy may undertake compounding as long ingredients (e.g., either finely ground product from an available
as they have appropriate facilities according to state-based tablet or injection or pharmaceutical-grade chemicals) would
legislation (e.g. allocated clean bench, specific compounding be required. One needs proper dispensing containers for the
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equipment). There should be a dedicated facility/room for medication. In short, a relationship with providers that carry
extemporaneous preparation. However, for pharmacies chemicals and supplies is important. Pharmacists have been
preparing small quantities of a limited range of products for using chemicals and other materials for prescription
immediate dispensing then a designated area or temporarily compounding throughout history. In the past, these chemicals
designated area is permissible. The area must be clearly and materials have been obtained from natural products, raw
demarcated during preparation. Measures must be taken to materials, and household ingredients. Today, compounding
reduce any risk of cross- contamination. Only one product pharmacists use chemicals from various reliable commercial
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should be handled at a time. Premises and equipment should sources, depending on their availability [9], [15-18].
be easy to clean. Following maintenance or repair, thorough
cleaning and, where appropriate, disinfection should take Documentation: These give processing, packaging and release
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place. Environmental conditions, including temperature, instructions. For products regularly prepared, master
humidity and lighting, must be adequate to permit safe and documents which combine the specification and product
comfortable preparation of medicinal products to limit the specific instructions should be produced and independently
degradation of ingredients. Facilities should be laid out in a way checked. Alternatively, a simple final product specification may
to provide adequate space for the activities undertaken. Work be produced in addition to the master document. Master
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should flow logically between working areas without the risk of documents should be clear and detailed and should have a
product cross- contamination. Complex compounding is standardized style within any one pharmacy. Simple stepwise
performed in a pressurized clean room using a laminar flow instructions for preparation, along with any specific notes or
cabinet, cytotoxic drug safety cabinet or an isolator. Many cautions (e.g. COSHH requirements) should be included on the
public and private hospitals maintain large aseptic master document for each product. A record should be kept of
compounding facilities to provide individualized dosing or the key stages of processing, packaging and release of products
commercially unavailable formulations. Areas and equipment to provide an audit trail of the quality relevant facts of the
should be cleaned effectively with a suitable detergent before history of an extemporaneous product during preparation. This
and after use. Equipment should be rinsed with an appropriate is normally achieved by completion of an individual worksheet,
grade of water after washing (potable or sterile water for usually by photocopying the master document. Worksheets will
irrigation/injection) and then dried. Critical surfaces should be vary for each pharmacy but should include: the name and
effectively sanitized with a suitable agent such as 70% alcohol formula of the product, and the source of the formula; a unique
before use. Sinks should be available for washing up of identification number to enable traceability; the manufacturer,
equipment, with separate facilities for handwashing. Sinks batch numbers of each starting material (or QC reference
should be a suitable distance away from the preparation areas number); the date of preparation etc. Labels must comply with
to reduce the risk of microbial contamination from water all statutory and professional requirements, and should include

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the following information: the name of the product, and compounding (Table 1). Simple compounding can be
where necessary the nature of the salt and any waters of performed by any pharmacist and is a core competency of
crystallization; quantity and strength of active ingredients; the pharmacy training. Complex compounding requires additional
pharmaceutical form etc. [6], [20]. training and evidence, as described by the Pharmacy Board of
Australia’s guidelines on compounding. Finland, Italy, and
Types of Compounding Scotland prepared mainly powder, while Belgium, Croatia,
Active pharmaceutical ingredients can be incorporated into a France, and Switzerland prepared mainly capsules. Practice in
wide array of products including creams, eye drops, nasal Germany, Spain, and Slovenia involved preparation of a less
sprays, oral dosage forms or intravenous infusions. In Australia, well-defined combination of liquid, powders, and capsules.
products may be classified into simple or complex

Table 1. Classification of simple versus complex compounding [5]

Type Explanation Examples
Simple All pharmacists have training during their Topical creams, ointments, lotions, gels, e.g. steroids,
undergraduate degree to prepare these hormones, coal tar, cholestyramine.
products. Oral liquids (solutions, suspensions, emulsions, mixtures,
Involves well-established preparations elixirs), tinctures, e.g. omeprazole suspension. Capsules,

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published in reputable literature, e.g. the tablets, powders, e.g. ethinylestradiol capsules.
Australian Pharmaceutical Formulary and Suppositories, pessaries, e.g. paracetamol, clotrimazole
Handbook, or formulae for which some data

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are available regarding quality, stability,
safety, efficacy and rational design.
Complex Pharmacists require further postgraduate Parenterals, e.g. morphine, clonidine. Ingredients with a
training in association with self-assessment safety hazard, e.g. cytotoxics, hormones
of relevant competencies and Single unit micro-dose (<25 mg of drug or no more than
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documentation of the specific 25% w/v of a dosage form), e.g. naltrexone. Modified-
competencies in a continuing professional release dosage forms, e.g. levothyroxine (T4),
development plan. Specialized facilities progesterone capsules
(sterile room with positive pressure) and Ophthalmic preparations, e.g. phenylephrine,
equipment (laminar flow isolator, dry heat tropicamide, ciprofloxacin
sterilization oven) are also required.
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Ambulatory-Care Compounding: If individuals can walk, they is so diverse and involves so many disciplines that sometimes it
are considered mobile or ambulatory (i.e., they are not is difficult to understand it; and, it changes rapidly. Also,
bedridden). Consequently, most pharmacists are involved in ambulatory care could generally encourage a team approach to
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ambulatory care, and most ambulatory patients are health improvement, prevention, health maintenance, risk
outpatients. Actually, the term can also be applied to home- assessment, early detection, management, curative therapy,
care patients and even institutionalized patients who are and rehabilitation. Ambulatory care offers various
mobile. One general characteristic of ambulatory patients is opportunities for individualizing patient care through
that they are generally responsible for obtaining their own pharmaceutical compounding. In fact, it is the area where most
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medication, storing it, preparing it (if necessary), and taking it. compounding pharmacists’ practice. Pharmacists’ roles in
It seems almost incongruous that in health care today as we ambulatory care patients can include, among others
become more aware that patients are individuals, respond as
individuals, and must be treated as individuals that some • Dispensing
health-care providers appear to be grouping patients into • Compounding
categories. They are grouped in categories for treatment, for • Counseling
reimbursement from a third party, or for determining levels of • Minimizing medication errors
care in managed-care organizations and using fixed-dose • Compliance enhancement
products provided by pharmaceutical manufacturers that are • Therapeutic drug monitoring
available because the marketing demand is sufficiently high to • Minimizing expenditures
justify their manufacture and production. Why should the
availability or the lack of availability of a specific economically Most reimbursement for ambulatory patients comes from the
profitable commercially available product dictate the therapy dispensing or the compounding process. Little financial
of a patient? Pharmacists have an opportunity to extend their consideration is given to counseling, minimizing medication
activities in patient care as the emphasis continues to shift from errors, compliance enhancement and therapeutic monitoring.
inpatient care to ambulatory care. Ambulatory care, however, However, these activities are important and should be

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performed. Because of the unique nature of compounded

medications, counseling is an absolute must for these patients. Nuclear Pharmacy Compounding: Nuclear pharmacy is a
From the above discussion of the activities of ambulatory care specialty practice of pharmacy that has been defined as a
pharmacists, it should be evident that extemporaneous patient-oriented service that embodies the scientific
compounding can be vitally important in ambulatory patient knowledge and professional judgment required for improving
care [6], [18-21] and promoting health through assurance of the safe and
efficacious use of radioactive drugs for diagnosis and therapy.
Hospital Pharmacy Compounding: The ever-present Radioactive drugs, commonly referred to as
responsibility of the health-care industry is to provide the best radiopharmaceuticals, are a special class of drugs that are
available care for the patient, using the best means to do so, regulated by the FDA. They are unique in that they contain an
and providing that care in a conducive environment. This must unstable nuclide (radioactive nuclide) as a part of the
be sufficiently economical to not put the institution in jeopardy compound designed to localize in an organ or tissue. Since
of being unable to continue to provide the services to the radiopharmaceuticals are radioactive, the Nuclear Regulatory
community they serve. This requires cooperation on the part of Commission or a similar state agency is involved in regulatory
the hospital administration, the medical staff, and the matters relevant to radiopharmaceuticals [25-27].
employees (nurses and pharmacists in particular as regards to
medication usage) and must involve the patient. One of the Risk Management

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effective means by which hospitals, and therefore hospital Legal Background: Pharmacists must comply with all legislation
pharmacies, can meet these challenges is to consider expanding relevant to the practice of pharmacy in the jurisdiction where
extemporaneous compounding services within the hospital the practice occurs. Failure to practice in accordance with these

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pharmacy. Pharmaceutical care and pharmaceutical requirements may give rise to action by one or more
compounding can provide cost savings to the hospital while responsible authorities. These matters may then be referred to
providing needed options to the physician through problem- the Board for appropriate action under the National Law or law
solving approaches and stimulating the hospital pharmacist of a co-regulatory jurisdiction. Non-compliance with these
through new challenges that allow the expression of both their guidelines and the practice standards and guidelines relevant
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skills and their art [15], [22,23] to compounding may also be notified directly to the Board for
appropriate action under the National Law or law of a co-
Veterinary Compounding: The first symposium on veterinary regulatory jurisdiction. Non-compliance may be reported by an
compounding was a significant forum for discussion by experts individual lodging a notification form, or through other means
and was a pivotal point in the history of veterinary such as notification of outcomes of audits carried out by a
compounding, occurring in September 1993. the meeting was state/territory pharmacy premises regulatory authority or
important because it assembled an impressive group of experts responsible body [5].
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on veterinary compounding, who then set about explaining and

defining the roles of the veterinarian and the pharmacist [24].
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Exhibit 4. Examples of Pre-1938 Drugs That Remained on the Market as Unapproved Drugs [15]
Acetaminophen, codeine phosphate, and caffeine capsules and tablets Morphine sulfate oral solution and tablets
Amobarbital sodium capsules Nitroglycerin sublingual tablets
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Amyl nitrate inhalant Opium tincture

Chloral hydrate capsules, syrup, and suppositories Oxycodone tablets
Codeine phosphate injection, oral solution, and tablets Oxycodone hydrochloride oral solution
Codeine sulfate tablets Paregoric
Colchicine injection and tablets Phenazopyridine hydrochloride tablets
Digitoxin tablets Phenobarbital capsules, elixir, and tablets
Digoxin elixir and tablets Phenobarbital sodium injection
Ephedrine sulfate capsules and injection Pilocarpine hydrochloride ophthalmic solution
Ergonovine maleate injection and tablets Potassium bicarbonate effervescent tablets for oral
Ergotamine tartrate tablets solution
Hydrocodone bitartrate tablets Potassium chloride oral solution
Hydrocodone bitartrate, aspirin, and caffeine tablets Potassium gluconate elixir and tablets
Hydromorphone hydrochloride suppositories Potassium iodide oral solution
Levothyroxine sodium for injection Salsalate capsules
Sodium fluoride oral solution and tablets
Thyroid tablets

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Alternatives to extemporaneous preparation reproducibility. This is a major consideration when no

 Therapeutic substitution: The use of a licensed medicine suspending agents are used, especially when the person
from the same therapeutic classification should be administering the dose is inexperienced and the dose is
considered and may provide a better clinical option than small [31]. Milk has been explored as a vehicle in liquid
the use of an extemporaneously prepared medicine which formulations showing potential for solubilizing drugs while
has limited data to support its formulation and stability. maintaining the stability of the emulsified vehicle [32].
The use of a less potent steroid rather than diluting a  Cutting tablets: Tablets cannot be cut with great accuracy
potent agent is an example where a therapeutic alternative of dose and research suggests that the variability may
may eliminate the need for an extemporaneous range from 50% to 150% of the desired dose even when
preparation. There are great opportunities for oncology using commercially available tablet cutters.
pharmacists, as well as community pharmacists, as a  Use of a preparation intended for a different route: The
resource for educating and monitoring patients receiving use of a suitable preparation intended for a different route
oral chemotherapy to ensure dosing accuracy, safe of administration can sometimes be a practical alternative;
administration, and proper disposal of hazardous drugs. for example, the use of an injection solution orally, or an
Oncology pharmacists face a constant challenge with oral solution rectally. However, this practice has its own
patients who cannot swallow oral anticancer drugs, making inherent risks and the pharmacist should ensure that the
extemporaneous oral liquid preparation a requirement. presentation used will be absorbed by this route and that

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Improper extemporaneous preparation of these agents, it will be tolerated by the patient. When using an injection
especially with the traditional chemotherapy with a narrow by the oral route, consideration should be given to the
therapeutic index, may increase the risk of over- or under- possibility of rapid absorption and elevated peak levels, the

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dosing [28]. potential for rapid drug degradation due to exposure to
 Use of an imported product: The preparation selected gastric acid and problems with first-pass metabolism. The
should be licensed for use in a country with equivalent or pH of an injection should also be considered, as extremes
similar licensing arrangements and regulatory standards to of pH can adversely affect the gastric mucosa [20].
the UK (e.g. EU, Canada, Australia). This will provide the
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requesting pharmacist with assurance that the quality, Risks associated with extemporaneous preparation
safety and efficacy of the medicine have been reviewed by  Formulation failure: An insoluble drug suspended in a
a competent regulatory authority. Although clinicians do suitable vehicle may be less susceptible to drug
not doubt the efficacy and utility of captopril in managing degradation, but may settle out of the suspension over
children with heart failure, concerns exist about optimal time, leading to sedimentation and caking. In this state,
dosing schedules and toxicity. This formulation is licensed there will be a higher concentration of drug at the bottom
in the Bristol–Myers Squibb, Australia, but was not of the bottle than at the top. In 2006, the FDA conducted a
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available in the UK [29]. limited survey of compounded drugs. Of 36 samples tested

 Use of a `Special' manufactured in a MHRA licensed unit: by the FDA, 12 failed at least one quality test, for a failure
The benefit of purchasing a ‘Special’ is that the product rate of 33%. Further, oral hormone dosage forms
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should be made to a validated formula with supporting containing multiple active ingredients showed poor
stability data in accordance with the principles of GMP. content uniformity, with random variation in all three
Licensed ‘Specials’ units are regularly inspected by the active ingredients from capsule to capsule [8], [20].
MHRA to ensure these principles are upheld. However, the  Microbial contamination: The choice of preservative for a
purchasing pharmacist will still need to review the formulation needs to take into account a number of factors
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supporting documentation (e.g. specification, Certificate of including pH, physical compatibility and the intended
Analysis/Conformity, BSE/TSE statement) to assess patient group. Unpreserved preparations should be stored
whether the product is of appropriate quality. Information in a refrigerator and assigned a short shelf-life to limit
on Specials manufacturers is available in the BNF. Specials microbial growth. A maximum shelf-life of 7 days at 2–80C
may be used to meet a variety of patient needs, for should be assigned to unpreserved oral liquid preparations
example, for babies, children and older people, and in unless sufficient validation work has been carried out to
specific areas such as dermatology and palliative care [30]. support an extended shelf-life. Essential macronutrients
 Use of soluble or dispersible tablets: This practice presents and micronutrients infused via PN solutions are an
fewer health and safety risks than crushing tablets, which essential part of the care of infants and children who
can expose the carer to potentially harmful dusts via cannot or should not be fed enterally. Infants and children
inhalation. When dispersing tablets, the dose should be require a greater amount of fat in their diet than do adults
prepared and administered immediately, as stability to support growth and development. The use of IVFE
cannot be guaranteed. It should be noted that slow or provides a concentrated source of calories and prevents
modified release preparations should not be used in this the development of essential fatty acid deficiency in
manner. If the active is not soluble, it can lead to inaccuracy neonates fed exclusively via the parenteral route. The AAP
of dosing through a lack of dose uniformity and recommends IVFE doses of up to 3 g/kg/day

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(approximately 30 kcal/kg/day) for use in infants. A variety  Patient acceptability issues: Consideration should be given
of microorganisms have been found in residual IVFE after to the palatability and presentation of oral liquid medicines
completion of the infusion [33]. Microorganisms could as there is a good argument that taste is crucial to achieving
potentially be introduced during reformulation of non- good compliance in children, especially for the treatment
sterile products. For example, if Candida albicans is of longstanding conditions such as in cardiology.
inadvertently introduced into freshly prepared multi-dose Extemporaneously prepared oral drug formulations can
citric acid solutions that are to be used orally for cough also be plagued by poor palatability characteristics which
reflex testing, immunocompromised individuals could can compromise patient adherence. This lack of child-
become infected. Regular monitoring of the environment, friendly formulations affects 40% of the global population,
equipment and procedures is essential to ensure quality subjecting pediatric patients to avoidable adverse drug
and sterility is maintained. The consequences of failure can events, reduced compliance with medication regimens,
be catastrophic, for example methylprednisolone limited access to new medications, and prolonged
injections from a single compounding pharmacy in the USA treatable illnesses. The pressing need for child-friendly,
resulted in 137 cases of Aspergillus fumigatus meningitis palatable medications suitable for administration to both
and 12 deaths [2]. infants and young children has been stressed (through
 Calculation errors: Common calculation errors associated regulatory guidance) by both the European Medicines
with extemporaneous preparation include errors when Agency and the US FDA. Prednisone is a bitter-tasting

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converting units from one to another (e.g. milligrams to corticosteroid used for its anti-inflammatory and
micrograms, conversions from weight in volume to immunosuppressant effects to treat a wide variety of
millimoles). Dangers of potent ingredients and calculation conditions in both adults and children. For pediatric

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errors, particularly where the strength of one or more patients, an alternative form of administration can be
ingredient is stated in a historical or non-standard fashion. produced by crushing solid oral prednisone formulations in
Similar reports have originated from the US, with the death order to avoid swallowing difficulties and/or achieve
of a child from a super-potent imipramine liquid, and a five- weight-based dosing. This approach, however, creates
year-old child who received a 1,000-fold overdose of extremely poor taste and mouth feel properties which are
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clonidine. Problems can also arise when doses can be objectionable to pediatric patients. While these limitations
prescribed as free base or salt, leading to potential can be somewhat mitigated by the use of proprietary oral
calculation errors when making and administering liquid formulations of prednisone, such products still retain
preparations (e.g. two-fold errors if caffeine citrate is their profoundly bitter taste characteristics. It is estimated
confused with caffeine base). Some of these errors have that approximately half of children refuse to take even a
been attributed to inconsistent labelling approaches, for liquid form of prednisone, with the large majority of those
example, strengths expressed per millilitre or per 5ml reporting bad taste as the single major reason for non-
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spoonful. Clinical pharmacists in pediatrics and compliance. Efforts to mask flavors using sweetening
neonatology help in dose calculation and dosage form agents, coatings, agglomeration, or microencapsulation
modification. The increased need for calculations and often result in poorly-controlled, heterogeneous particle
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dilutions of pediatric medicines, and a requirement to size distributions that result in a gritty or granular mouth
adjust dose of an individual patient based on age, feel and can provide ineffective taste masking,
gestational age, weight and surface area, provide a greater characteristics that may also compromise patient
opportunity for a clinical pharmacist in medication acceptance. The design of an ideal paediatric formulation
management process. They can help to prepare needs to consider the following factors: (i) producing
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pediatric/neonatal formulary [34], [41]. minimal impact on the lifestyle of the child, manifesting as
 Starting materials: Care should also be taken with the use the lowest dosage frequency and a palatable product, (ii)
of cariogenic sugars (e.g. sucrose) in pediatric formulations provision of individualized dosing or dose banding
as it has been associated with dental cavities. It is therefore appropriate for effective therapy, (iii) sufficient
important to list all such excipients on the product label so bioavailability, (iv) non-toxic excipients in the formulation,
that end-users are made aware of their presence in the (v) convenient and reliable administration and (vi) robust
formulation. In a 2004 published analysis sponsored by STD production process at minimal cost [20], [36-39].
Pharmaceuticals, all samples purchased from three  Health and safety risks: When handling hazardous
compounding pharmacies failed content testing for a 3% products, units should be equipped with suitable
sodium tetradecyl sulfate solution for injection (range containment devices and systems should be put in place to
2.59–3.39). Significant concentrations of the contaminant eliminate the risk of cross-contamination.
carbitol were found to be present in samples from all three  Therapeutic risks and clinical consequences: Any
sources (0.33–4.18), suggesting possible use of a non- inaccuracy of dosing associated with medicines that have a
pharmaceutical grade chemical [35]. narrow therapeutic index can lead to significant morbidity,
whether due to under-dosing leading to treatment failure
or overdosing leading to toxicity. By contrast, any

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inaccuracy of dosing associated with drugs with a wide Coupled with this, extemporaneous preparations may not
therapeutic index may have little or no impact on the be routinely identified as high-risk therapies by
therapy. pharmacists and therefore such treatments are not
 Associated clinical risk factors: The majority of patients commonly given the level of scrutiny and close monitoring
receiving extemporaneously prepared products, in they require. Therefore, when embarking on the use of an
particular oral liquid medicines, tend to be from vulnerable extemporaneously prepared product, the pharmacist
patient groups (e.g. neonates, children, stroke victims) who should ensure that systems are in place to monitor the
are either unaware of ill-effects associated with their effectiveness of the therapy [20].
treatment or who cannot communicate with their clinician.

Exhibit 5. Extemporaneous preparation or compounding standards as set out in the Medicines [44]
 A product is extemporaneously prepared only when there is no product with a marketing authorization available and
where you are able to prepare the product in compliance with accepted standards.
 Staff involved are competent to undertake the tasks to be performed.
The requisite facilities and equipment are available. Equipment must be maintained in good order to ensure that

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
performance is unimpaired, and must be fit for the intended purpose.
 The professional associate (Pharmacist) is satisfied as to the safety and appropriateness of the formula of the product.
 Ingredients are sourced from recognized pharmaceutical manufacturers and are of a quality accepted for use in the

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preparation and manufacture of pharmaceutical products. Where appropriate, relevant legislation must be complied
with.
 Particular attention and care are paid to substances which may be hazardous and require special handling techniques.
 The product is labelled with the necessary particulars, including an expiry date and any special requirements for the safe
handling or storage of the product.
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 If you are undertaking large-scale preparation of medicinal products, all relevant standards and guidance are adhered
to.
 Records are kept for a minimum of 2 years. The records must include: the formula; the ingredients; the quantities used;
their source; the batch number; the expiry date; where the preparation is dispensed in response to a prescription, the
patient’s and prescription details and the date of dispensing; the personnel involved, including the identity of the
pharmacist taking overall responsibility.
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Risk Management
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The European Pharmacopoeia monograph on Pharmaceutical should be judged on a case-by-case basis. Consideration should
Preparations specifies the necessity for tests to be applied to be given to the individual patient’s age and condition, whether
particular dosage forms, as described in their respective dosage the product will be ingested or used topically, as well as the
form monographs, which are also applicable in the case of potency of, and risk posed by, the active substances and/or
extemporaneously prepared products. The requirements on excipients. Where it is not practical to carry out this testing (e.g.
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testing in the European Pharmacopeia monograph deal with due to the batch size, urgency, etc.), other suitable methods
the appearance of products, identity and purity tests, should be implemented to ensure that the appropriate quality
uniformity and reference standards. The extent of quality is achieved, in accordance with the risk assessment carried out.
control applied to a product should be proportionate with the At a minimum, the starting materials and finished product
level of risk the finished product could pose to the patient and should be examined visually before supply to a patient [40].

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Exhibit 6. Reference texts and other sources of information relevant to compounding

• Martindale: The Complete Drug Reference
• Trissel’s Stability of Compounded Formulations - Trissel LA
• International Journal of Pharmaceutical Compounding (www.ijpc.com)
• Australian Don’t Rush to Crush Handbook - The Society of Hospital Pharmacists of Australia
• Handbook on Injectable Drugs - American Society of Health - System Pharmacists
• Pharmaceutical Calculations - Howard C. Ansel and Mitchell J. Stoklosa
• The Art, Science and Technology of Pharmaceutical Compounding - Loyd Allen
• Australian Injectable Drugs Handbook - The Society of Hospital Pharmacists of Australia
• Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems - Loyd Allen
• Remington: The Science and Practice of Pharmacy, edited by David B. Troy, Paul Beringer
• Guide to Good Manufacturing Practice for Medicinal Products (can be accessed from the TGA website)
• Guidelines for the Safe Prescribing, Dispensing and Administration of Cancer Chemotherapy (can be accessed from
the Clinical Oncological Society of Australia website)

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Role of the Pharmacists Conclusion
Compounding preparations extemporaneously on lawful Pharmacy compounding provides pharmacists with a unique
prescription for individual patients is within the pharmacist’s opportunity to practice their time-honored profession. It is

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purview. Pharmacists and pharmacies are licensed and becoming an even more important part of pharmacy practice in
inspected by the states; if a state inspection uncovers the future, including those involved in community and hospital
“manufacturing under the guise of compounding,” it refers the care, nursing care, home care, veterinary and other specialty
matter to the FDA, which can apply cGMP expectations to the practices. It is a practice where the clinical expertise can be
pharmacist/pharmacy. When a pharmacist engages in large- merged with the scientific expertise of pharmacists to make a
scale production of preparations without prescription or visible pharmaceutical care. Pharmacists are to be encouraged
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evidence of pending refills, trending, etc, the practice can be more in compounding but should be aware of the core of
regarded as manufacturing; cGMP compliance will be expected, formulating a specific drug product for a specific patient. This is
including an approved NDA or ANDA. Today, however, important in providing pharmaceutical care.
compounding pharmacies have begun to flourish and are once
again becoming a vital component of pharmacy practice. Many Article Summary
health care professionals recognize that, for some specific It is important to use a pharmacist’s expertise to adjust dosage
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patient populations, there is a growing need to compound quantities, frequencies, and even dosage forms for enhanced
certain medications because they are not available through compliance. All pharmacists should understand the options
conventional manufacturing methods. Whereas the services presented by compounding. Pharmaceutical compounding is
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provided by compounding pharmacies give many patients increasing for a number of reasons, including the availability of
options with regard to drug therapy, compounding pharmacists a limited number of dosage forms for most drugs, a limited
must be properly trained to specialize in this aspect of number of strengths of most drugs, home health care, hospice,
pharmacy practice and must have the appropriate resources the non-availability of drug products/combinations,
and references to compound quality medications. Pharmacists discontinued drugs, drug shortages, orphan drugs, new
are responsible for ensuring that extemporaneous preparations therapeutic approaches and special patient populations.
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are compounded according to compounding guidelines and Extemporaneously compounded medicines may be useful when
standards with respect to purity, quality, stability, packing, a required dose or dose form is unavailable commercially, or for
record keeping, and other appropriate pharmacy practices. individualized dosing. There are numerous established
Compounding pharmacists must work closely with the compounding formulae available, and new formulae may be
prescribing physician to ensure that patient goals are met. A developed with the help of formulation guidelines and
positive therapeutic outcome for the patient is the professional advice. Unlike registered medicines, compounded
fundamental goal for all health care professionals, and, with preparations have not generally been assessed for safety and
that goal in mind, the services provided by compounding efficacy. Their use is off label and is based on extrapolation from
pharmacies can continue to make pharmacists an indispensable the component ingredients. Short-term expiry dates are
part of the health care team [42,43]. provided for compounded products unless their stability has
been assessed.

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