Comprehensive pharmacy review: Pharmaceutical Principles and Drug Dosage Forms Flashcards
1
Q
- Which substance is classified as a weak electrolyte?
(A) glucose
(B) urea
(C) ephedrine
(D) sodium chloride
(E) sucrose
A
- Th e answer is C [see IV.A.1.a; IV.A.3.d].
Glucose, urea, and sucrose are nonelectrolytes. Sodium
chloride is a strong electrolyte. Electrolytes are
substances that form ions when dissolved in water.
Thus, they can conduct an electric current through the
solution. Ions are particles that bear electrical charges:
Cations are positively charged, and anions are negatively
charged. Strong electrolytes are completely ionized
in water at all concentrations. Weak electrolytes
(e.g., ephedrine) are only partially ionized at most concentrations.
Because nonelectrolytes do not form ions
when in solution, they are nonconductors.
2
Q
- The pH value is calculated mathematically as the
(A) log of the hydroxyl ion (OH) concentration.
(B) negative log of the OH concentration.
(C) log of the hydrogen ion (H
) concentration.
(D) negative log of the H
concentration.
(E) ratio of H
/OH concentration.
A
- Th e answer is D [see IV.A.3.b].
Th e pH is a measure of the acidity, or hydrogen ion
concentration, of an aqueous solution. Th e pH is the
logarithm of the reciprocal of the hydrogen ion (H
)
concentration expressed in moles per liter. Because the
logarithm of a reciprocal equals the negative logarithm
of the number, the pH is the negative logarithm of the
H
concentration. A pH of 7.0 indicates neutrality. As
the pH decreases, the acidity increases. Th e pH of arterial
blood is 7.35 to 7.45; of urine, 4.8 to 7.5; of gastric
juice, approximately 1.4; and of cerebrospinal fl uid,
7.35 to 7.40. Th e concept of pH was introduced by
Sörensen in the early 1900s. Alkalinity is the negative
logarithm of [OH] and is inversely related to acidity.
3
Q
- Which property is classified as colligative?
(A) solubility of a solute
(B) osmotic pressure
(C) hydrogen ion (H
) concentration
(D) dissociation of a solute
(E) miscibility of the liquids
A
- Th e answer is B [see IV.A.2.d].
Osmotic pressure is an example of a colligative property.
Th e osmotic pressure is the magnitude of pressure
needed to stop osmosis across a semipermeable
membrane between a solution and a pure solvent. Th e
colligative properties of a solution depend on the total
number of dissociated and undissociated solute particles.
Th ese properties are independent of the size of
the solute. Other colligative properties of solutes are
reduction in the vapor pressure of the solution, elevation
of its boiling point, and depression of its freezing
point.
4
Q
- Th e colligative properties of a solution are related
to the
(A) pH of the solution.
(B) number of ions in the solution.
(C) total number of solute particles in the solution.
(D) number of un-ionized molecules in the solution.
(E) pKa of the solution.
A
- Th e answer is C [see IV.A.1.b].
Th e colligative properties of a solution are related to
the total number of solute particles that it contains.
Examples of colligative properties are the osmotic
pressure, lowering of the vapor pressure, elevation of
the boiling point, and depression of the freezing or
melting point
5
Q
- Th e pH of a buff er system can be calculated with the
(A) Noyes–Whitney equation.
(B) Henderson–Hasselbalch equation.
(C) Michaelis–Menten equation.
(D) Young equation.
(E) Stokes equation
A
- Th e answer is B [see IV.A.3.e].
Th e Henderson–Hasselbalch equation for a weak acid
and its salt is as follows:
pH pKa
log _ [[ascaildt]]
where pKa is the negative log of the dissociation constant
of a weak acid and [salt]/[acid] is the ratio of the
molar
6
Q
- Which mechanism is most oft en responsible for
chemical degradation?
(A) racemization
(B) photolysis
(C) hydrolysis
(D) decarboxylation
(E) oxidation
A
- Th e answer is C [see V.D.1].
Although all of the mechanisms listed can be responsible,
the chemical degradation of medicinal compounds,
particularly esters in liquid formulations, is
usually caused by hydrolysis. For this reason, drugs
that have ester functional groups are formulated in dry
form whenever possible. Oxidation is another common
mode of degradation and is minimized by including
antioxidants (e.g., ascorbic acid) in drug formulations.
Photolysis is reduced by packaging susceptible products
in amber or opaque containers. Decarboxylation,
which is the removal of COOH groups, aff ects compounds
that include carboxylic acid. Racemization
neutralizes the eff ects of an optically active compound
by converting half of its molecules into their mirrorimage
confi guration. As a result, the dextrorotatory
and levorotatory forms cancel each other out. Th is type
of degradation aff ects only drugs that are characterized
by optical isomerism.
7
Q
- Which equation is used to predict the stability of a
drug product at room temperature from experiments
at accelerated temperatures?
(A) Stokes equation
(B) Young equation
(C) Arrhenius equation
(D) Michaelis–Menten equation
(E) Hixson–Crowell equation
A
- Th e answer is C [see V.E.3.d].
Testing of a drug formulation to determine its shelf life
can be accelerated by applying the Arrhenius equation
to data obtained at higher temperatures. Th e method
involves determining the rate constant (k) values for
the degradation of a drug at various elevated temperatures.
Th e log of k is plotted against the reciprocal of
the absolute temperature, and the k value for degradation
at room temperature is obtained by extrapolation.
8
Q
- Based on the relation between the degree of ionization
and the solubility of a weak acid, the drug aspirin
(pKa 3.49) will be most soluble at
(A) pH 1.0.
(B) pH 2.0.
(C) pH 3.0.
(D) pH 4.0.
(E) pH 6.0.
A
- Th e answer is E [see IV.A.3.g].
Th e solubility of a weak acid varies as a function of pH.
Because pH and pKa (the dissociation constant) are
related, solubility is also related to the degree of ionization.
Aspirin is a weak acid that is completely ionized
at a pH that is two units greater than its pKa. Th erefore,
it is most soluble at pH 6.0.
9
Q
- Which solution is used as an astringent?
(A) strong iodine solution USP
(B) aluminum acetate topical solution USP
(C) acetic acid NF
(D) aromatic ammonia spirit USP
(E) benzalkonium chloride solution NF
A
Th e answer is B [see VI.B.7].
Aluminum acetate and aluminum subacetate solutions
are astringents that are used as antiperspirants and
as wet dressings for contact dermatitis. Strong iodine
solution and benzalkonium chloride are topical antibacterial
solutions. Acetic acid is added to products as
an acidifi er. Aromatic ammonia spirit is a respiratory
stimulan
10
Q
- Th e particle size of the dispersed solid in a suspension
is usually greater than
(A) 0.5 microm.
(B) 0.4 microm.
(C) 0.3 microm.
(D) 0.2 microm..
(E) 0.1 microm.
A
- Th e answer is A [see IV.B.1.a].
A suspension is a two-phase system that consists of a
fi nely powdered solid dispersed in a liquid vehicle. Th e
particle size of the suspended solid should be as small
as possible to minimize sedimentation, but it is usually
0.5 microm.
11
Q
- In the extemporaneous preparation of a suspension,
levigation is used to
(A) reduce the zeta potential.
(B) avoid bacterial growth.
(C) reduce particle size.
(D) enhance viscosity.
(E) reduce viscosity.
A
- Th e answer is C [see VI.E.3.a].
Levigation is the process of blending and grinding a
substance to separate the particles, reduce their size,
and form a paste. Levigation is performed by adding
a small amount of suitable levigating agent (e.g.,
glycerin) to the solid and blending the mixture with a
mortar and pestle.
12
Q
- Which compound is a natural emulsifying agent?
(A) acacia
(B) lactose
(C) polysorbate 20
(D) polysorbate 80
(E) sorbitan monopalmitate
A
- Th e answer is A [see VI.D.3].
Acacia, or gum arabic, is the exudate obtained from
the stems and branches of various species of Acacia, a
woody plant native to Africa. Acacia is a natural emulsifying
agent that provides a stable emulsion of low
viscosity. Emulsions are droplets of one or more immiscible
liquids dispersed in another liquid. Emulsions are
inherently unstable: Th e droplets tend to coalesce into
larger and larger drops. Th e purpose of an emulsifying
agent is to keep the droplets dispersed and prevent
them from coalescing. Polysorbate 20, polysorbate 80,
and sorbitan monopalmitate are also emulsifi ers, but
are synthetic, not natural, substances.
13
Q
- Vanishing cream is an ointment that may be
classifi ed as
(A) a water-soluble base.
(B) an oleaginous base.
(C) an absorption base.
(D) an emulsion base.
(E) an oleic base.
A
- Th e answer is D [see VI.E.2].
Ointments are typically used as emollients to soft en
the skin, as protective barriers, or as vehicles for
medication. A variety of ointment bases are available.
Vanishing cream, an emulsion type of ointment base, is
an oil-in-water emulsion that contains a high percentage
of water. Stearic acid is used to create a thin fi lm on
the skin when the water evaporates.
14
Q
- Rectal suppositories intended for adult use usually
weigh approximately
(A) 1 g.
(B) 2 g.
(C) 3 g.
(D) 4 g.
(E) 5 g
A
- Th e answer is B [see VI.F.2.a].
By convention, a rectal suppository for an adult weighs
approximately 2 g. Suppositories for infants and children
are smaller. Vaginal suppositories typically weigh
approximately 5 g. Rectal suppositories are usually
shaped like an elongated bullet (cylindrical and tapered
at one end). Vaginal suppositories are usually ovoid.
15
Q
- In the fusion method of making cocoa butter
suppositories, which substance is most likely to be
used to lubricate the mold?
(A) mineral oil
(B) propylene glycol
(C) cetyl alcohol
(D) stearic acid
(E) magnesium silicate
A
15Th e answer is A [see VI.F.4.c].
In the fusion method of making suppositories, molds
made of aluminum, brass, or nickel–copper alloys are
used. Finely powdered drug mixed with melted cocoa
butter is poured into a mold that is lubricated very
lightly with mineral oil.
16
Q
- A very fi ne powdered chemical is defi ned as one that
(A) completely passes through a #80 sieve.
(B) completely passes through a #120 sieve.
(C) completely passes through a #20 sieve.
(D) passes through a #60 sieve and not more than
40% through a #100 sieve.
(E) passes through a #40 sieve and not more than
60% through a #60 sieve.
A
- Th e answer is B [see VI.G; Table 2-8].
Th e USP defi nes a very fi ne chemical powder as one
that completely passes through a standard #120 sieve,
which has 125-m openings. Th e USP classifi cation
for powdered vegetable and animal drugs diff ers from
that for powdered chemicals. To be classifi ed as very
fi ne, powdered vegetable and animal drugs must pass
completely through a #80 sieve, which has 180-m
openings.
17
Q
- Which technique is typically used to mill camphor?
(A) trituration
(B) levigation
(C) pulverization by intervention
(D) geometric dilution
(E) attrition
A
17 Th e answer is C [see VI.G.1.c.(3.(b)].
Pulverization by intervention is the milling technique
that is used for drug substances that are gummy and
tend to reagglomerate or resist grinding (e.g., camphor,
iodine). In this sense, intervention is the addition of
a small amount of material that aids milling and can
be removed easily aft er pulverization is complete. For
example, camphor can be reduced readily if a small
amount of volatile solvent (e.g., alcohol) i
18
Q
- The dispensing pharmacist usually blends potent
powders with a large amount of diluent by
(A) spatulation.
(B) sift ing.
(C) trituration.
(D) geometric dilution.
(E) levigation.
A
- Th e answer is D [see VI.G.2.c].
Th e pharmacist uses geometric dilution to mix potent
substances with a large amount of diluent. Th e potent
drug and an equal amount of diluent are fi rst mixed
in a mortar by trituration. A volume of diluent equal
to the mixture in the mortar is added, and the mix is
again triturated. Th e procedure is repeated, and each
time, diluent equal in volume to the mixture then in the
mortar is added, until all of the diluent is incorporated.
19
Q
- Which type of paper best protects a divided
hygroscopic powder?
(A) waxed paper
(B) glassine
(C) white bond
(D) blue bond
(E) vegetable parchment
A
- Th e answer is A [see VI.G.3.b.(4)].
Hygroscopic and volatile drugs are best protected by
waxed paper, which is waterproof. Th e packet may be
double-wrapped with a bond paper to improve the
appearance of the completed powder.
20
Q
- Which capsule size has the smallest capacity?
(A) 5
(B) 4
(C) 1
(D) 0
(E) 000
A
- Th e answer is A [see VI.H.2.c.(1)].
Hard capsules are numbered from 000 (largest) to 5
(smallest). Th eir approximate capacity ranges from 600
to 30 mg; however, the capacity of the capsule depends
on the density of the contents.
21
Q
- Th e shells of soft gelatin capsules may be made elastic
or plastic-like by the addition of
(A) sorbitol.
(B) povidone.
(C) polyethylene glycol (PEG).
(D) lactose.
(E) hydroxypropyl methylcellulose.
A
- Th e answer is A [see VI.H.3.a–b].
Th e shells of soft gelatin capsules are plasticized by
the addition of a polyhydric alcohol (polyol), such as
glycerin or sorbitol. An antifungal preservative can
also be added. Both hard and soft gelatin capsules can
be fi lled with a powder or another dry substance. Soft
gelatin capsules are also useful dosage forms for fl uids
or semisolids.
22
Q
- Th e United States Pharmacopeia (USP) content
uniformity test for tablets is used to ensure which
quality?
(A) bioequivalency
(B) dissolution
(C) potency
(D) purity
(E) toxicity
A
- Th e answer is C [see VI.H.4.a].
A content uniformity test is a test of potency. To ensure
that each tablet or capsule contains the intended
amount of drug substance, the USP provides two tests:
weight variation and content uniformity. Th e content
uniformity test can be used for any dosage unit but is
required for coated tablets, for tablets in which the active
ingredient makes up 50% of the tablet, for suspensions
in single-unit containers or in soft capsules,
and for many solids that contain added substances. Th e
weight variation test can be used for liquid-fi lled soft
capsules, for any dosage form unit that contains at least
50 mg of a single drug if the drug makes up at least
50% of the bulk, for solids that do not contain added
substances, and for freeze-dried solutions
23
Q
- All of the following statements about chemical
degradation are true except
(A) as temperature increases, degradation decreases.
(B) most drugs degrade by a fi rst-order process.
(C) chemical degradation may produce a toxic
product.
(D) chemical degradation may result in a loss of
active ingredients.
(E) chemical degradation may aff ect the therapeutic
activity of a drug.
A
- Th e answer is A [see V.A and V.B].
Th e reaction velocity, or degradation rate, of a pharmaceutical
product is aff ected by several factors, including
temperature, solvents, and light. Th e degradation rate
increases two to three times with each 10°C increase in
temperature. Th e eff ect of temperature on reaction rate
is given by the Arrhenius equation:
k AeEa/RT
where k is the reaction rate constant, A is the frequency
factor, Ea is the energy of activation, R is the gas constant,
and T is the absolute temperature.
24
Q
- All of the following statements concerning zero-order
degradation are true except
(A) its rate is independent of the concentration.
(B) a plot of concentration versus time yields a
straight line on rectilinear paper.
(C) its half-life is a changing parameter.
(D) its concentration remains unchanged with respect
to time.
(E) the slope of a plot of concentration versus time
yields a rate constant.
A
- Th e answer is D [see V.B.2.a].
In zero-order degradation, the concentration of a drug
decreases over time. However, the change of concentration
with respect to time is unchanged. In the equation
ddCt k
the fact that dC/dt is negative signifi es that the concentration
is decreasing. However, the velocity of the
concentration change is constant.
25
Q
- All of the following statements about fi rst-order
degradation are true except
(A) its rate is dependent on the concentration.
(B) its half-life is a changing parameter.
(C) a plot of the logarithm of concentration versus
time yields a straight line.
(D) its t90% is independent of the concentration.
(E) a plot of the logarithm of concentration versus
time allows the rate constant to be determined
A
- Th e answer is B [see V.B.2.b.(2)].
Th e half-life (t½) is the time required for the concentration
of a drug to decrease by one-half. For a fi rst-order
degradation:
t½ 0.6k9 3
Because both k and 0.693 are constants, t½ is a constant.
26
Q
- A satisfactory suppository base must meet all of the
following criteria except
(A) it should have a narrow melting range.
(B) it should be nonirritating and nonsensitizing.
(C) it should dissolve or disintegrate rapidly in the
body cavity.
(D) it should melt 30°C.
(E) it should be inert.
A
- Th e answer is D [see VI.F.3].
A satisfactory suppository base should remain fi rm
at room temperature. Preferably, it should not melt
30°C to avoid premature soft ening during storage
and insertion. It should also be inert, nonsensitizing,
nonirritating, and compatible with a variety of drugs.
Moreover, it should melt just below body temperature
and should dissolve or disintegrate rapidly in the fl uid
of the body cavity into which it is inserted.
27
Q
- Cocoa butter (theobroma oil) exhibits all of the
following properties except
(A) it melts at temperatures between 33°C and 35°C.
(B) it is a mixture of glycerides.
(C) it is a polymorph.
(D) it is useful in formulati
A
- Th e answer is E [see VI.F.3.c.(1)].
Cocoa butter is a fat that is obtained from the seed of
Th eobroma cacao. Chemically, it is a mixture of stearin,
palmitin, and other glycerides that are insoluble
in water and freely soluble in ether and chloroform.
Depending on the fusion temperature, cocoa butter
can crystallize into any one of four crystal forms.
Cocoa butter is a good base for rectal suppositories,
although it is less than ideal for vaginal or urethral
suppositories.
28
Q
- United States Pharmacopeia (USP) tests to ensure the
quality of drug products in tablet form include all of
the following except
(A) disintegration.
(B) dissolution.
(C) hardness and friability.
(D) content uniformity.
(E) weight variation.
A
- Th e answer is C [see VI.I.5].
To satisfy the USP standards, tablets are required to
pass one of two tests. A weight variation test is used if
the active ingredient makes up the bulk of the tablet.
A content uniformity test is used if the tablet is coated
or if the active ingredient makes up 50% of the
bulk of the tablet. Many tablets for oral administration
are required to meet a disintegration test. Disintegration
times are specifi ed in the individual monographs.
A dissolution test may be required instead if the active
component of the tablet has limited water solubility.
Hardness and friability would aff ect the disintegration
and dissolution rates, but hardness and friability tests
are in-house quality control tests, not offi cial USP tests.
29
Q
- Forms of water that are suitable for use in parenteral
preparations include
I. purifi ed water USP.
II. water for injection USP.
III. sterile water for injection USP.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is D (II, III) [see VI.A.1].
Water for injection USP is water that has been purifi
ed by distillation or by reverse osmosis. Th is water is
used to prepare parenteral solutions that are subject
to fi nal sterilization. For parenteral solutions that are
prepared aseptically and not subsequently sterilized,
sterile water for injection USP is used. Sterile water for
injection USP is water for injection USP that has been
sterilized and suitably packaged. Th is water meets the
USP requirements for sterility. Bacteriostatic water for
injection USP is sterile water for injection USP that
contains one or more antimicrobial agents. It can be
used in parenteral solutions if the antimicrobial additives
are compatible with the other ingredients in the
solution, but it cannot be used in newborns. Purifi ed
water USP is not used in parenteral preparations
30
Q
- The particles in an ideal suspension should satisfy
which of the following criteria?
I. Their size should be uniform.
II. They should be stationary or move randomly.
III. They should remain discrete
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is E (I, II, III) [see IV.B.2].
An ideal suspension would have particles of uniform
size, minimal sedimentation, and no interaction between
particles. Although these ideal criteria are rarely
met, they can be approximated by keeping the particle
size as small as possible, the densities of the solid and
the dispersion medium as similar as possible, and the
dispersion medium as viscous as possible.
31
Q
- The sedimentation of particles in a suspension can be
minimized by
I. adding sodium benzoate.
II. increasing the viscosity of the suspension.
III. reducing the particle size of the active
ingredient.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- The answer is D (II, III) [see IV.B.2].
As Stokes’s law indicates, the sedimentation rate of a
suspension is slowed by reducing its density, reducing
the size of the suspended particles, or increasing its
viscosity by incorporating a thickening agent. Sodium
benzoate is an antifungal agent and would not reduce
the sedimentation rate of a suspension
32
Q
- Ingredients that may be used as suspending agents
include
I. methylcellulose.
II. acacia.
III. talc.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is C (I, II) [see VI.C.3].
Acacia and methylcellulose are common suspending
agents. Acacia is a natural product, and methylcellulose
is a synthetic polymer. By increasing the viscosity
of the liquid, these agents enable particles to remain
suspended for a longer period.
33
Q
- Mechanisms that are thought to provide stable
emulsifi cations include the
I. formation of interfacial fi lm.
II. lowering of interfacial tension.
III. presence of charge on the ions.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is E (I, II, III) [see VI.D.3].
Emulsifying agents provide a mechanical barrier to
coalescence. Th ey also reduce the natural tendency of
the droplets in the internal phase (oil or water) of the
emulsion to coalesce. Th ree mechanisms appear to be
involved. Some emulsifi ers promote stability by form-
ing strong, pliable interfacial fi lms around the droplets.
Emulsifying agents also reduce interfacial tension.
Finally, ions (from the emulsifi er) in the interfacial
fi lm can lead to charge repulsion that causes droplets
to repel one another, thereby preventing coalescence.
34
Q
- Nonionic surface-active agents used as synthetic
emulsifi ers include
I. tragacanth.
II. sodium lauryl sulfate.
III. sorbitan esters (Spans).
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is B (III) [see VI.D.3].
All of the substances listed are emulsifying agents,
but only sorbitan esters are nonionic synthetic agents.
Tragacanth, like acacia, is a natural emulsifying agent.
Sodium lauryl sulfate is an anionic surfactant. Sorbitan
esters (known colloquially as Spans because of their trade
names) are hydrophobic and form water-in-oil emul-
sions. Th e polysorbates (known colloquially as Tweens)
are also nonionic, synthetic sorbitan derivatives. How-
ever, they are hydrophilic and therefore form oil-in-water
emulsions. Sodium lauryl sulfate, as alkali soap, is also
hydrophilic and thus forms oil-in-water emulsions
35
Q
- Advantages of systemic drug administration by rectal
suppositories include
I. avoidance of fi rst-pass eff ects.
II. suitability when the oral route is not feasible.
III. predictable drug release and absorption.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- The answer is C (I, II) [see VI.F.1–2].
Rectal suppositories are useful for delivering systemic
medication under certain circumstances. Absorption of
a drug from a rectal suppository involves release of the
drug from the suppository vehicle, diff usion through
the rectal mucosa, and transport to the circulation
through the rectal veins. Th e rectal veins bypass the
liver, so this route avoids rapid hepatic degradation of
certain drugs (fi rst-pass eff ect). Th e rectal route is also
useful when a drug cannot be given orally (e.g., because
of vomiting). However, the extent of drug release and
absorption is variable. It depends on the properties of
the drug, the suppository base, and the environment in
the rectum
36
Q
- True statements about the milling of powders include
I. a fi ne particle size is essential if the lubricant is
to function properly.
II. an increased surface area may enhance the
dissolution rate.
III. milling may cause degradation of thermolabile
drugs.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is E (I, II, III) [see VI.G.1.c].
Milling is the process of mechanically reducing the
particle size of solids before they are formulated into a
fi nal product. To work eff ectively, a lubricant must coat
the surface of the granulation or powder. Hence, fi ne
particle size is essential. Decreasing the particle size
increases the surface area and can enhance the dissolu-
tion rate. Th ermolabile drugs may undergo degrada-
tion because of the buildup of heat during milling.
37
Q
- Substances used to insulate powder components that
liquefy when mixed include
I. talc.
II. kaolin.
III. light magnesium oxide.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- The answer is D (II, III) [see VI.G.2.a.(2)].
Some solid substances (e.g., aspirin, phenylsalicylate,
phenacetin, thymol, camphor) liquefy or form eutectic
mixtures when in close, prolonged contact with one
another. Th ese substances are best insulated by the
addition of light magnesium oxide or magnesium
carbonate. Other inert diluents that can be used are
kaolin, starch, and bentonite.
38
Q
- A ceramic mortar may be preferable to a glass
mortarwhen
I. a volatile oil is added to a powder mixture.
II. colored substances (dyes) are mixed into a
powder.
III. comminution is desired in addition to mixing.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is B (III) [see VI.G.2.b].
When powders are mixed, if comminution is especially
important, a porcelain or ceramic mortar that has a
rough inner surface is preferred over the smooth work-
ing surface of a glass mortar. Because a glass mortar
cleans more easily aft er use, it is preferred for chemi-
cals that may stain a porcelain or ceramic mortar as
well as for simple mixing of substances that do not
require comminution.
39
Q
- Divided powders may be dispensed in
I. individual-dose packets.
II. a bulk container.
III. a perforated, sift er-type container.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is A (I) [see VI.G.3.a–b].
Powders for oral use can be dispensed by the pharma-
cist in bulk form or divided into premeasured doses
(divided powders). Divided powders are traditionally
dispensed in folded paper packets (chartulae) made
of parchment, bond paper, glassine, or waxed paper.
However, individual doses can be packaged in metal
foil or small plastic bags if the powder needs greater
protection from humidity or evaporation.
40
Q
- True statements about the function of excipients used
in tablet formulations include
I. binders promote granulation during the wet
granulation process.
II. glidants help promote the fl ow of the tablet
granulation during manufacture.
III. lubricants help the patient swallow the tablets.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is C (I, II) [see VI.I.2.b].
Tablets for oral ingestion usually contain excipients
that are added to the formulation for their special
functions. Binders and adhesives are added to promote
granulation or compaction. Diluents are fi llers that are
added to make up the required tablet bulk. Th ey can
also aid in the manufacturing process. Disintegrants
aid in tablet disintegration in gastrointestinal fl uids.
Lubricants, antiadherents, and glidants aid in reduc-
ing friction or adhesion between particles or between
tablet and die. For example, lubricants are used in the
manufacture of tablets to reduce friction when the tab-
let is ejected from the die cavity. Lubricants are usually
hydrophobic substances that can aff ect the dissolution
rate of the active ingredient.
41
Q
- Which manufacturing variables would be likely
to aff ect the dissolution of a prednisone tablet in
thebody?
I. the amount and type of binder added
II. the amount and type of disintegrant added
III. the force of compression used during tableting
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is E (I, II, III) [see VI.2.b.(3)].
Disintegrants are added to tablet formulations to facili-
tate disintegration in gastrointestinal fl uids. Disintegra-
tion of the tablet in the body is critical to its dissolution
and subsequent absorption and bioavailability. Th e
binder and the compression force used during tablet
manufacturing aff ect the hardness of the tablet as well as
tablet disintegration and drug dissolution.
42
Q
- Agents that may be used to coat enteric-coated tablets
include
I. hydroxypropyl methylcellulose.
II. carboxymethylcellulose.
III. cellulose acetate phthalate.
A if I only is correct
B if III only is correct
C if I and II are correct
D if II and III are correct
E if I, II, and III are correct
A
- Th e answer is B (III) [see VI.I.3.a.(4)].
An enteric-coated tablet has a coating that remains
intact in the stomach, but dissolves in the intestines
to yield the tablet ingredients there. Enteric coatings
include various fats, fatty acids, waxes, and shellacs.
Cellulose acetate phthalate remains intact in the
stomach because it dissolves only when the pH - Other enteric-coating materials include povidone
(polyvinylpyrrolidone), polyvinyl acetate phthalate,
and hydroxypropyl methylcellulose phthalate.
43
Q
Directions for questions 43–46: Each of the following
tablet-processing problems can be the result of one of
the following reasons. The processing problems may
be used more than once or not at all. Choose the best
answer, A–E.
- Picking
A excessive moisture in the granulation
B entrapment of air
C tablet friability
D degraded drug
E tablet hardness
A
It occurs when particles from the formulation adhere to the punch cup, resulting in defective tablets. Picking is a specific type of sticking that refers to particles getting stuck in or around the logo/characters embossed on the punch face.
A excessive moisture in the granulation
44
Q
- Mottling
A excessive moisture in the granulation
B entrapment of air
C tablet friability
D degraded drug
E tablet hardness
A
Mottling is the term used to describe an unequal distribution of color on a tablet, with light or dark spots standing out on an otherwise uniform surface. This type of tablet defect occurs in tablet formulation with a dry coloring agent
D degraded drug
45
Q
- Capping
A excessive moisture in the granulation
B entrapment of air
C tablet friability
D degraded drug
E tablet hardness
A
Capping can be either formulation- or process-driven. In the formulation, there can be issues with interparticle bonding, too little moisture, or too many fines in the segregation.
B entrapment of air
46
Q
- Sticking
A excessive moisture in the granulation
B entrapment of air
C tablet friability
D degraded drug
E tablet hardness
A
Sticking is one of the most common problems tablet manufacturers encounter. Sticking describes the buildup of granules on the punch-tip face, which can be caused by several factors, including the formulation’s physicochemical properties and the surface characteristics of the punch face.
- The answer is A [see VI.I.4].
Sticking is adhesion of tablet material to a die wall.
It may be caused by excessive moisture or by the use
of ingredients that have low melting temperatures.
Mottling is uneven color distribution. It is most oft en
caused by poor mixing of the tablet granulation but
may also occur when a degraded drug produces a col-
ored metabolite. Capping is separation of the top or
bottom crown of a tablet from the main body. Capping
implies that compressed powder is not cohesive.
Reasons for capping include excessive force of com-
pression, use of insuffi cient binder, worn tablet tooling
equipment, and entrapment of air during processing.
Picking is adherence of tablet surface material to a
punch. It can be caused by a granulation that is too
damp, by a scratched punch, by static charges on the
powder, and particularly by the use of a punch tip that
is engraved or embossed.
47
Q
Directions for questions 47–49: Each of the following
processes can be described by one of the following
comminution procedures. Th e processes may be used more
than once or not at all. Choose the best answer, A–E.
- Rubbing or grinding a substance in a mortar that has a
rough inner surface
A trituration
B spatulation
C levigation
D pulverization by intervention
E tumbling
A
A trituration
48
Q
- Reducing and subdividing a substance by adding an
easily removed solvent
A trituration
B spatulation
C levigation
D pulverization by intervention
E tumbling
A
D pulverization by intervention
49
Q
- Adding a suitable agent to form a paste and then
rubbing or grinding the paste in a mortar
A trituration
B spatulation
C levigation
D pulverization by intervention
E tumbling
A
- The answer is C [see VI.G.1.c; VI.G.2].
Comminution is the process of reducing the par-
ticle size of a powder to increase its fi neness. Several
comminution techniques are suitable for small-scale
use in a pharmacy. Trituration is used both to com-
minute and to mix dry powders. If comminution is
desired, the substance is rubbed in a mortar that has
a rough inner surface. Pulverization by intervention
is oft en used for substances that tend to agglomerate
or resist grinding. A small amount of easily removed
(e.g., volatile) solvent is added. Aft er the substance is
pulverized, the solvent is allowed to evaporate or is
otherwise removed. Levigation is oft en used to prepare
pastes or ointments. Th e powder is reduced by adding
a suitable nonsolvent (levigating agent) to form a paste
and then either rubbing the paste in a mortar with a
pestle or rubbing it on an ointment slab with a spatula.
Spatulation and tumbling are techniques that are used
to mix or blend powders, not to reduce them. Spatula-
tion is blending small amounts of powders by stirring
them with a spatula on a sheet of paper or a pill tile.
Tumbling is blending large amounts of powder in a
large rotating container
50
Q
Directions for questions 50–53: Each of the following
controlled-release dosage forms is represented by one
of the following drug products. Th e dosage forms may
be used more than once or not at all. Choose the best
answer,A–E.
A matrix formulations
B ion-exchange resin complex
C drug complexes
D osmotic system
E coated beads or granules
- Ionamin capsules
A
B ion-exchange resin complex
51
Q
- Thorazine Spansule capsules
A matrix formulations
B ion-exchange resin complex
C drug complexes
D osmotic system
E coated beads or granules
A
E coated beads or granules
52
Q
- Rynatan pediatric suspension
A matrix formulations
B ion-exchange resin complex
C drug complexes
D osmotic system
E coated beads or granules
A
C drug complexes
53
Q
- Procardia XL
A matrix formulations
B ion-exchange resin complex
C drug complexes
D osmotic system
E coated beads or granules
A
- The answer is D [see VI.K.3.d].
Controlled-release dosage forms are designed to re-
lease a drug slowly for prolonged action in the body.
A variety of pharmaceutical mechanisms are used to
provide the controlled release. Ion-exchange resins
may be complexed to drugs by passing a cationic drug
solution through a column that contains the resin.
Th e drug is complexed to the resin by replacement of
hydrogen atoms. Release of drug from the complex
depends on the ionic environment within the gastroin-
testinal tract and on the properties of the resin. Coated
beads (e.g., Th orazine Spansule capsules) or granules
produce blood levels similar to those obtained with
multiple dosing. Th e various coating thicknesses pro-
duce a sustained-release eff ect.
Matrix devices may use insoluble plastics, hydrophilic
polymers, or fatty compounds. Th ese components are
mixed with the drug and compressed into a tablet. Th e
primary dose, or the portion of the drug to be released
immediately, is placed on the tablet as a layer or coat.
Th e remainder of the dose is released slowly from the
matrix. Relatively insoluble tannate–amine complexes
provide for a prolonged gastrointestinal absorption
phase and sustained systemic concentrations of the
weak bases. Osmotic systems employ osmotic pressure
to control the release of the active ingredient from the
formulation. Osmotic tablet formulations provide a
semipermeable membrane as a coating that surrounds
the osmotically active core. Th e coating allows water
to diff use into the core but does not allow drug to dif-
fuse out. As water fl ows into the tablet, the drug dis-
solves. Th e laser-drilled hole in the coating allows the
drug solution within the tablet to fl ow to the outside at
a rate that is equivalent to the rate of water fl ow into the
tablet. Th e osmotic pressure gradient and a zero-order
drug-release rate will be maintained as long as excess
osmotically active solute (e.g., electrolyte) remains in
the tablet core.
