Download Pharmacist`s Role in Managing Special Patient Needs Related to

Pharmacist’s Role in Managing Special
Patient Needs Related to Excipients
Lindsay Snyder, PharmD, Pharmacy Practice resident, Blanchard Valley Medical Associates; Teresa Hoffman,
PharmD, site preceptor; and Kelly Shields, PharmD, drug information specialist, ONU preceptor
Objectives
At the completion of this article, the reader should be able to:
1. Define inactive ingredients
2. Describe the purpose of inactive ingredients
3. Identify populations in which inactive ingredients are
of concern
4. Recognize potential inactive ingredient problems in
those populations
5. Formulate a plan to respond to inquiries about inactive
ingredients
Introduction
Patients may not be aware of the role inactive ingredients play
in the production of medications. Medication compounding
or manufacture requires much more than just an active drug,
other components or “inactive ingredients” serve multiple
functions in the creation of effective dosage forms. Also named
excipients, inactive ingredients may serve as coloring agents,
fillers, diluents, preservatives, flavorings, sweeteners, solvents,
lubricants, or vehicles. Such ingredients typically make up the
majority of the mass or volume of a drug preparation, often five
to ten times more than the mass of the active drug.1 Excipients
are not only used in prescription drugs but also over-thecounter medications, vitamins, herbal products, or other dietary
supplements.
The FDA lists 10,437 inactive ingredients for human use as of
2008.2 Inactive ingredients are considered pharmacologically
inert; however, they may pose problems to certain populations
of patients. Types of patients who are especially vulnerable to
the risks of inactive ingredients are patients with food allergies,
pregnant women, children, or patients with medical dietary
restrictions.
These patient populations should avoid certain excipients for a
myriad of different reasons. Possibly the most obvious reason
is an allergy to an agent. Food allergies preclude the use of
products containing derivatives of the allergen. Patients with
drug allergies can have similar allergic reactions to certain
dyes or sweeteners. Patients may be unable to use products
containing alcohol due to pregnancy, previous ethanol abuse,
or drug interactions. Medically necessary dietary restrictions
such as gluten-free or ketogenic diets can also complicate
medication selection. Religious sensitivities may also be taken
into account because some common inactive ingredients may
be animal-derived.
It would seem that careful label reading would allow patients
to avoid these excipients; however, problematic excipients may
not be obviously stated on food or drug labeling. One common
reason is that patients may not recognize the myriad of names
under which a product may be listed. Also, substances used
in manufacturing processes may not be listed as ingredients.
Cross-contamination during production could possibly be an
issue when multiple products are manufactured on the same line
or in the same facility. Even though drug manufacturing confers
less risk of cross-contamination than food manufacturing due
to stringent regulations, cross-contamination can still be a
significant risk for patients.
Every pharmacist must be prepared to recognize and handle
potential excipient problems because the pharmacist is
typically the first person contacted for applicable information.
Additionally, pharmacists are uniquely qualified to address
these issues due to their training in pharmaceutics and their
awareness of the variety of available dosage forms in which
medications are available. This article provides a brief review
of situations that may require excipient avoidance as well as
corresponding management strategies.
Food Allergies and Intolerances
Food allergies or intolerances are an increasingly common
complication in medication selection. Although reasons for
the recent national rise in food allergies are poorly understood,
more than 12 million Americans (about 4%) currently have
food allergies.3 Though patients may not always recognize the
difference, allergies and intolerances are classified based on the
general mechanism of reaction.
Figure 1
European Academy of Allergology and Clinical
Immunology classification of adverse food reactions4
The majority of food allergies are IgE-mediated reactions.4 In
2003, the National Institutes of Health reported that 6-8% of
children and 2% of adults had experienced IgE-mediated food
allergy.5 The most common food allergens are listed in Table
1. Allergic reactions mediated by IgE are characterized by
acute urticaria, atopic dermatitis, or anaphylactic symptoms.6
Reactions that begin minutes after allergen contact occur
primarily through histamine release from basophils. Late phase
reactions, beginning four to six hours later, can last for several
days.4
Food allergies may also be immune-mediated without being
solely due to IgE. Other antibody isotypes, immune complexes
formed by the food and an antibody to the food, or cellmediated immune responses may be involved. For example, the
autoimmune destruction of small intestine villi in response to
gluten in celiac disease is T-cell mediated.6
Food intolerance, also called food sensitivity, may occur
by several mechanisms including infections, enzyme
abnormalities, or pharmacologic properties of foods. For
example, an infection such as giardiasis may appear as
intolerance to food. Lactose intolerance is caused by an
abnormality of the lactase enzyme in the gastrointestinal tract.
Pharmacologic food reactions can be caused by naturally
occurring vasoactive amines such as histamine, dopamine,
tyramine, phenylethylamine, serotonin, or norepinephrine.
Reactions to vasoactive amines may manifest as paresthesias,
burning sensation, headache, and/or pruritis.6
Table 1
Most Common IgE-mediated Food Allergens6
Children
Adults
Egg
Shellfish
Milk
Tree nuts
Soy
Peanuts
Wheat
Fish
Peanuts
Food allergies and intolerances are often managed by strict
avoidance of the allergen. Label reading becomes a significant
component of food safety for these patients and also relates
to drug safety. Detailed allergen labeling has become more
common as labeling laws have become more stringent. The
Food Allergen Labeling and Consumer Protection Act took
effect on January 1, 2006, requiring the eight most common
allergens (as listed in Table 1) to be disclosed in plain language
on the label. These requirements apply even if the allergens are
present in coloring, flavoring, or spices.7 The FDA continues
to seek information from both manufacturers and consumers to
improve allergen labeling.8
Ingredient nomenclature may make it difficult to identify
ingredients that could pose a problem for food allergic patients.
For example, if a patient is allergic to corn, and the label lists
“starch” as an inactive ingredient, it may be overlooked by
the patient as a potential source of allergenic corn protein. If
label information is vague or the sources of ingredients are not
listed, it may be necessary to contact the manufacturer for more
information. Most companies will be able to provide some sort
of allergen information, even if it is accompanied by a standard
disclaimer statement. It is also important to obtain information
about manufacturing processes and any substances used in
production that are not listed as ingredients.
Pregnancy and Pediatrics
Although information on medication use during pregnancy is
slowly accumulating, the fetal safety of inactive ingredients
is largely unstudied. Some excipients are known to be
problematic in pregnancy. Aluminum-containing aspirins
and antacids pose a problem for pregnant women because
aluminum is systemically absorbed, crosses the placenta, and
can accumulate in the fetus. Aluminum has caused intoxication,
neurologic symptoms, or osteopenia in newborns.1
The common inactive ingredients methylcellulose, polyethylene
glycol (PEG), and polysorbate have undergone fetal safety
testing in animals, but there is no conclusive human research
for safety in pregnancy. A study of methylcellulose given
to pregnant rats resulted in diaphragm abnormalities. Low
molecular weight PEG compounds have caused congenital
defects in mice and maternal toxicity in rabbits. Large
molecular weight PEG (4000) has been studied for treatment
of constipation in pregnant patients from 6-38 weeks gestation
and appears to be safe. Polysorbate has been tested in numerous
animal teratogenicity studies with mixed results. Using any of
these products in pregnancy requires weighing the risks and
benefits of treatment with the sparse available safety data.1
Benzyl alcohol is a preservative often used in parenteral
products due to useful local anesthetic properties and poor
palatability.9 Benzyl alcohol has been implicated in fatal
“gasping syndrome” in premature neonates, characterized
by hypotension, bradycardia, cardiovascular collapse, and
metabolic acidosis. Gasping syndrome does not occur in
infants older than 3 months, but hypersensitivity reactions
including nausea, contact dermatitis, and angioedema can occur
in older patients. Both the FDA and the American Academy
of Pediatrics recommend against administering preparations
preserved with benzyl alcohol to infants.10
Propylene glycol is a dihydroxy alcohol used as a
pharmaceutical solvent, preservative, and humectant.
Propylene glycol metabolism relies on alcohol and aldehyde
dehydrogenase enzymes which may be inadequate for
elimination in infants, children younger than 4, pregnant
women, patients with renal or hepatic dysfunction, and patients
taking disulfiram or metronidazole. These enzymes do not reach
full capacity until children are 12 to 30 months old. Propylene
glycol should be avoided in the above patient groups to prevent
potential adverse effects such as hypotension, arrhythmia, or
hemolysis.10
Ethanol, a known human teratogen and neurotoxin, is used in
some liquid drug preparations. The ethanol threshold for fetal
effects is unknown, but the small doses found in medications
may be safe because of rapid maternal metabolism.1 Some
elixir dosage formulations of medications for pediatric use may
contain high concentrations of ethanol, for example Norvir®
oral solution. Children are particularly affected by ethanol, with
its well known adverse effects of CNS depression, confusion,
and GI upset being more pronounced in children than other
populations.10 Ethanol must also be avoided by those taking
other medications that would cause a disulfiram-like reaction
when combined with ethanol (ex. metronidazole). Patients with
a history of alcohol abuse may also want minimize exposure to
ethanol in medications.9
Religious Sensitivities
Gelatin and stearic acid are commonly used inactive
ingredients that are derived from animal sources. Specific
sources of an excipient (ex. porcine, bovine) may vary from
product to product, even from one lot to another. This may
raise issues with patients because of religious beliefs. For
example, consumption of pork products is forbidden in
Judaism and Islam due to restrictions specified in the religious
documents. Pork is also discouraged in some forms of
Orthodox Christianity and in Seventh Day Adventist churches.
Consumption of beef products can be controversial in Hinduism
and Buddhism. Religious leaders are often responsible for
determining what is acceptable for their individual religious
groups, and they may make exceptions based on medical
necessity. Patients are less likely to be adherent to medication
regimens if they are concerned that they may contain
religiously controversial ingredients.11 Pharmacists can help
patients determine whether their medications are acceptable
according to religious standards by obtaining more information
on the source of the animal product.
At times it may be difficult for even the manufacturing
company to determine a source of gelatin or stearic acid, so
alternative methods for dealing with religious sensitivities
may be necessary. Because the inactive ingredients among
similar drug products vary, another generic or brand name
formulation that does not contain gelatin or stearic acid could
be an alternative to the product in question. Many sustained
release formulations contain gelatin, so switching a patient to
appropriately timed immediate release preparations could solve
the problem. Liquid preparations may be another alternative,
as gelatin and stearic acid are primarily used in tablets or
capsules. If other delivery systems such as transdermal
patches or suppositories are available, they might also be
appropriate choices. Depending on specific manufacturer
recommendations, some drug powders could be removed from
gelatin capsules before consumption. Because some religions
also prohibit touching certain animal products, religious
advisors may also need to be consulted before the powder from
a gelatin capsule is consumed.11 Individually compounded
preparations could be another potential solution, although this
option may be too cost prohibitive for some patients.
Celiac Disease
Celiac disease is a genetically-linked autoimmune disorder
that affects the small intestine in response to ingested
gluten. Gluten proteins are found in wheat, barley, and rye.
Although oats do not contain gluten peptides, they are often
contaminated with gluten during growing and processing. It
is controversial as to whether celiac patients can tolerate pure,
uncontaminated oats, although certified gluten-free oats tested
by ELISA assay have recently become available. Up to 1% of
Americans may have celiac disease, but experts have estimated
that 95% of cases are currently undiagnosed.12 Symptoms are
often variable and can include malabsorption syndromes (ex.
osteoporosis, iron-deficiency anemia), GI symptoms (bloating,
diarrhea, constipation, abdominal pain, or dyspepsia), fatigue,
depression, or dermatitis herpetiformis among many other
symptoms. Diagnosis is often difficult due to variability in
patient presentation, and celiac disease is frequently subject
to misdiagnosis. Treatment is a strict gluten-free diet, which
includes gluten-free medications.13
companies surveyed produced gluten-free products according
to company policy. Many companies were hesitant to confirm
the gluten status of their products in general, and some would
only comment that no wheat, barley, rye, or oats were added
to the product. Because many ingredient suppliers assessed in
the survey did not guarantee gluten-free raw materials, some
companies would not guarantee a gluten-free product without
specific testing for the presence of gluten.14 Although food
processing and preparation can lead to cross-contamination,
it is unlikely to occur during the highly regulated drug
manufacturing process.15 Ultimately, each company will
place the responsibility of choosing a gluten-free product
on the patient and physician even though the access to some
information necessary for such decisions may be limited by the
drug company.
As the number of patients diagnosed with celiac disease
increases, more patients will be requesting information about
gluten-free medications. Some patients, while not diagnosed
with celiac disease, may have a food intolerance to gluten and
must also minimize or avoid gluten in food and medications.
In addition to assistance with prescription and over the counter
medications, pharmacists may play a role in helping this patient
population by specifically identifying gluten-free vitamins and
dietary supplements. Because of past or present malabsorption,
celiac patients may wish to supplement iron, calcium, or other
nutrients that could be deficient. Pharmacists can be a vital
resource for selecting appropriate products.
Gluten-containing excipients can be difficult to recognize.
Excipients that could potentially contain gluten include
starches, dextrates or dextrins, alcohols, caramel coloring, or
barley-based brown rice syrup. These excipients can all be
derived from gluten-free sources (ex. potato, rice, corn, or
tapioca), but any such ingredient that does not list a glutenfree source on the label could potentially contain gluten.
Many starch products made in the US come from gluten-free
sources. For example, sodium starch glycolate manufactured
in the US is usually derived from potato starch. It is important
to consider, however, that some US drug companies may
obtain ingredients from other countries. The ingredients of two
common over-the-counter products are listed in Figure 2; the
ingredients that might require more investigation to ensure the
product is gluten-free are listed in bold type.
Figure 2: Example Product Labels
Tylenol® Tablets
Active Ingredient:
Acetaminophen
325 mg in each tablet
Inactive Ingredients:
Cellulose, corn starch,
magnesium stearate,
sodium starch
glycolate.
Motrin® IB Caplets
Active Ingredient: Ibuprofen
200mg in each caplet
Inactive Ingredients: carnauba
wax, colloidal silicon dioxide,
corn starch, FD&C yellow
#6, hypromellose, iron
oxide, magnesium stearate,
polydextrose, polyethylene
glycol, pregelatinized starch,
propylene glycol, shellac, stearic
acid, titanium dioxide
As more people have been diagnosed with celiac disease,
gluten information has become more available due to the
need to assist these patients. In 2001, 5 of 100 pharmaceutical
Ketogenic Diet
The ketogenic diet is used as a treatment for patients with
intractable seizure disorders, especially children. Although
the exact anticonvulsant mechanism is unknown, this high
lipid, low carbohydrate, and low protein diet in a 4:1 or 3:1
gram ratio leads to ketosis.16 Incomplete metabolism of fatty
acids into ketone bodies produces acetone, acetoacetic acid,
and α-hydroxybutyrate. Research into the anticonvulsive
mechanism is ongoing, and it is hypothesized that the effect is
not due to one single mechanism.17
Many patients take additional seizure medication along with
the ketogenic diet. Since the diet is mostly used in children,
and many of the children have swallowing difficulties, liquid
medication preparations are frequently used. Carbohydrates
from prescription medication can cause a problem because the
total daily carbohydrate allowance for children 1-10 years on
the ketogenic diet is 5-15 g. For example, one formulation of
valproic acid syrup contains 20 grams of carbohydrates in a
daily dose.16
Many excipients can contain other carbohydrates or proteins
in addition to sugar–the more obvious culprit. It is important
to remember that the words “sugar free” on the label does
not mean that the product is free of carbohydrates. The most
significant carbohydrate contributors are sucrose, fructose,
sorbitol, glycerin, and alcohols, although the effect of ethyl
alcohol on the ketogenic diet is unknown. Information
about carbohydrate content may also be useful for patients
with diabetes, metabolic disorders, alcohol intolerance, or
gastrointestinal diseases.
Table 2: Carbohydrate-containing Excipients
Sweeteners
Other sugars
Misc.
Sucrose, fructose, sorbitol, mannitol, xylitol,
aspartame, saccharin, corn syrup
Glucose, dextrose, lactulose
Alcohols, glycerin, cellulose
Planning ahead is essential to manage the carbohydrate
contribution of medications to the allowed intake of the
ketogenic diet. Include maintenance medication carbohydrates
in the daily calculated carbohydrate totals. Plan for situations
where additional medication might be quickly needed such
as allergies, fever, or infection by knowing in advance which
medications are available as low-carbohydrate formulations. If
low carbohydrate formulations are not readily available, diet
adjustments may be needed to allow for the carbohydrates from
short-term medications.18
Sweetening agents can cause problem for additional patient
populations. Sugar alcohols—sorbitol, mannitol, and xylitol—
are commonly used as sweeteners in diabetic or lower-calorie
foods. Medications containing large amounts of sugar alcohols
may cause gas, bloating, or diarrhea. They are poorly absorbed
in the gastrointestinal tract and are acted upon by colonic
bacteria, causing osmotic diarrhea. Many oral liquid drug
formulations use sorbitol as a vehicle and sweetener. Patients
who receive large amounts of liquid medications, such as
those receiving tube feedings, are at risk for sorbitol-induced
diarrhea.19 Often, diarrhea associated with tube feeding is
incorrectly blamed on the enteral solution itself when the
medication formulations may be the true cause.20
Diarrhea can be a confusing symptom for patients with celiac
disease or lactose intolerance because it can be a sign of
gluten or lactose ingestion, respectively. If severe, diarrhea
may preclude further use of sorbitol-containing medication,
oftentimes on the assumption that the active drug itself is the
cause. Switching to a formulation with no or less sorbitol may
alleviate the diarrhea and allow the patient to continue taking
the medication.
Aspartame is a combination of L-aspartic acid and
L-phenylalanine in methyl ester form. It is commonly found in
food and drug products as a sweetener.9 It is 200 times sweeter
than sugar, thus it contributes negligible caloric content if used
in typical amounts. The FDA has determined that aspartame is
safe based on review of more than 100 safety studies, although
aspartame has had questionable links to cancer development.21
Aspartame is definitely risky, however, for patients with
phenylketonuria (PKU) because it contains phenylalanine.
PKU is a genetic disorder causing difficulty metabolizing
phenylalanine, and phenylalanine can build up in the blood
of PKU patients over time. Untreated PKU can cause growth
failure, microcephaly, seizures and intellectual impairment
from the accumulation of toxic metabolic by-products. The
FDA requires PKU-specific labeling of all products containing
aspartame to alert phenylketonurics to the presence of
phenylalanine.21
Patients with sulfonamide allergies may also be sensitive
to some sweeteners. Aspartame, as well as the sweetener
saccharin, demonstrates cross-reactivity in patients allergic to
sulfonamides. Caution is advised if sulfa-allergic patients take
medications with these artificial sweeteners.28
Lactose Intolerance
Lactose is a disaccharide also known as milk sugar. Lactose
is found in dairy products and is also used as filler in many
medications due to palatability and water solubility.22 Ingested
lactose is broken down by lactase enzymes on the brush
border of the small intestine. Lactose intolerance results from
decreased activity or lack of lactase enzyme. When undigested
lactose reaches the colon, it can cause symptoms such as
bloating, flatulence, or diarrhea.
Lactose intolerance is common, affecting between 30 and
50 million Americans.23 Treatment consists of either lactose
avoidance or lactase enzyme supplementation. In a limited
number of case reports, diarrhea has been reported after
lactose-containing medications were started with an otherwise
lactose-free diet.24 As an excipient in medications, the amount
of lactose used is far smaller than that of standard portions
of dairy products in the diet. Interestingly, in a randomized,
double-blind, crossover study, self-identified severely lactose
intolerant patients attributed GI symptoms to lactose even
when lactose was not present in products they were receiving.
Thirty patients, 21 of whom were determined by hydrogen
breath tests to have lactose malabsorption, were given either
240mL of lactose-hydrolyzed or lactose-containing milk daily
with breakfast for one week each. Minimal gastrointestinal
symptoms were reported, and there were no significant
differences in GI symptoms between the lactose and lactosehydrolyzed formulations.22 As this study demonstrates, it
is difficult to definitively attribute GI symptoms to lactose
ingestion as well as to identify individual thresholds for lactose
intolerance. Whether the small amounts of lactose used as
inactive ingredients cause symptoms of lactose intolerance
is hard to determine; however, lactose in drug formulations
continues to be a concern for many patients who are severely
lactose intolerant.
Allergies to Preservatives or Dyes
Sulfiting agents are commonly used as preservatives due to
their antioxidant and antimicrobial properties. Even though they
are known to cause serious reactions, sulfites have generally
regarded as safe (GRAS) status and are used in many foods and
drugs. Reactions almost always occur with coexisting reactive
airway disease and can manifest as asthma exacerbations or
nonimmunologic anaphylactoid reactions.25 Contact dermatitis
is also a common reaction from sulfites in topical products.26
In the course of food processing, sulfites may be added to
salads, potatoes, dried fruits, beer, and wine among many other
products.26 The FDA prohibits sulfite use on fruits or vegetables
that are to be served or presented fresh to the public. They also
require proper labeling of any food product with detectable
sulfite levels, even if the sulfite is used as a processing aid.27
Sulfites may be added to drug products, often parenteral or
topical formulations, and the medications must be labeled
that they contain sulfites. For example some formulations of
ketoconazole, parenteral chlorpromazine, chlorpheniramine,
dopamine, and dexamethasone injections have added sulfites.
Because sodium metabisulfite prevents the oxidation of
epinephrine, it is often an ingredient in parenteral epinephrine
formulations, local anesthetics, and sympathomimetic eye
drops.26 Those who have a known sensitivity to sulfites should
avoid medications that contain them, making an exception
for injectable epinephrine in life-threatening anaphylactic
situations.25
The parabens, other commonly used preservatives, may cause
cross-reactivity in aspirin-sensitive patients and should be used
with caution. The paraben metabolite hydroxyparabenzoic acid
is structurally similar to aspirin, and anaphylactic reactions in
aspirin-sensitive patients have been reported.29
Tartrazine (FD&C yellow no. 5) and sunset yellow (FD&C
yellow no. 6) have demonstrated cross-reactivity with
aspirin, sodium benzoate, indomethacin, and other azo dyes.28
Tartrazine can produce a reaction similar to aspirin intolerance
including bronchospasm, urticaria, eosinophilia, or angioedema.
Although rare, nonimmunologic anaphylactoid reactions have
been reported. Between 2% and 20% of asthmatic individuals
are aspirin-sensitive, and tartrazine has been shown to be
particularly dangerous in aspirin-sensitive patients. Crossreactivity rates were once thought to be as high as 10%, but
more recent research suggests less than 2.4% cross-reactivity.25
Sunset yellow (FD&C yellow no. 6) has been associated in case
reports with gastrointestinal symptoms, with one case involving
eosinophilia and hives.
Aspirin-sensitive patients have also developed similar reactions
to other dyes including amaranth, erythrosine, indigo carmine
(FD&C blue no.2), ponceau, new coccine, brilliant blue
(FD&C blue no. 1), methyl blue, quinoline yellow, and FD&C
red no. 40. Dyes have also been purported to contribute to
hyperactivity in children, but controlled trials have not shown
such an association.25
Conclusion
Many patient populations must be considered in a discussion of
inactive ingredients, and there are more patient considerations
than can be addressed in this article. It may be difficult to
determine which drug products are appropriate in situations of
excipient intolerance.
The source with the most information is almost always the
drug company itself. When calling a drug company, make
sure to have in mind the questions that you would like to ask
or the clarifications you would like to make before calling.
It may be time-consuming to navigate automated answering
systems, but having to call back usually means doing it all
over again. Have the lot number of the drug handy, as inactive
sources can vary from one lot to another. Most companies will
provide information pertaining to a specific patient situation,
but they may not guarantee that the information will apply to
any future situations. Watch for clues to changes in inactives,
such as “new formulation” notices on product label. Make sure
to verify the status of the drug periodically, as the information
is typically only accurate at the time of inquiry. If responses
from drug companies are vague or seem like a legal disclaimer
with little usable information, ask specific questions about the
sources of individual inactive ingredients in a particular lot
of drug. Usually, someone at the company can provide this
information.
In addition to contacting a drug company, pharmacists may
be able to suggest therapeutic alternatives. Pharmacists can
evaluate other dosage forms such as liquid medications,
transdermal patches, a different generic or brand formulation,
or switching from extended-release to immediate-release
formulations. Compounded formulations may be an option if
suitable dosage forms are not commercially available. When
compounding, the pharmacist must also be aware of excipients
in each ingredient involved in product preparation and realize
that individualized drug formulations may be very costly to
the patient.
Sulfiting agents25
Sulfur dioxide
Sodium sulfite
Sodium bisulfite
Sodium metabisulfite
Potassium bisulfate
Potassium metabisulfite
Patients depend on their pharmacists—often their most
accessible health care providers—to assist in making important
decisions about medication suitability for their individual
situations. Pharmacists are uniquely positioned to evaluate drug
selection based on inactive ingredients. Understanding patient
needs as well as being familiar with drug formulations, dosage
forms, and sources of inactive ingredients make the pharmacist
an invaluable resource.