Pharmaceutical Sci Flashcards _ Quizlet.pdf

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The initial stability studies of
drugs are often conducted at
temperatures far above
intended storage conditions.
Such "accelerated stability
studies" are sometimes
criticized for their potential
inapplicability to the expected
real world storage. Defend the
use of such higher temperature
studies.
Since the desired storage stability of drugs is
usually 2 to 3 years, the development of stable
formulations would take an inordinate amount of
time if one were forced to use low temperature
long-term studies for their creation. By using
elevated temperature, it is hoped that the rates of
both physical and chemical degradation processes
can be increased to the point that they can be
quickly identified. Using this information, one can
then find conditions and excipients that slow these
processes sufficiently that they will produce stable
formulations over much longer periods at a lower
temperature. Although this approach does not
always work since events not detected under
accelerated conditions can potentially occur over
very long times, it has generally proven to be a
reliable approach.
Advanced drug delivery
systems and dosage forms are
one and the same.

a) This statement is TRUE.

b) This statement is FALSE.
The statement is false
Pharmaceutical Sci Study

What is the estimated t90 shelf-
life of an antibiotic when
refrigerated at 4oC when its
t90 is 8

hours at 25oC?
80 hours
If a drug in solution degrades
according to the equation, ln C
= ln 5 - 0.07t, where

concentration is mg/mL and
time is days, how many hours
will it take for the drug to

degrade to 90% of the C0?
36 hours
Describe the following types of
drug instability:

a) Hydrolysis b) Photolysis c)
Oxidation
a) Hydrolysis is a process in which drug molecules
interact with water molecules to

yield breakdown products (e.g., aspirin).

b) Photolysis is a chemical decomposition process
induced by light.

c) Oxidation is the loss of electrons from an atom or
a molecule. It involves an

increase in the number of carbon-to-oxygen bonds
in a molecule or a reduction

in the number of carbon-to-hydrogen bonds.

A new drug product is found to
be ineffective after it has
decomposed 10% (t90 shelf-
life). The original concentration
of one sample was 5.0 mg/mL.
When assayed 20 months later,
the concentration was found to
be 4.2 mg/mL.

a) Assuming that the
decomposition is first-order,
what should be the expiration
time on the label?

b) What is the half-life of this
product?
t90 = 0.105

k

k can be found using the equation lnC = lnC0 - kt
ln4.2 = ln5 - k(20)

k = 0.0087 month-1

t90 = 0.105 = 0.105 = 12.1 months k 0.0087

t1/2 = 0.693 = 0.693 = 79.7 months k 0.0087
Drug X degrades by a zero-
order process with a rate
constant of 0.05 mg/mL/year at
room

temperature. If a 1% w/v
solution is prepared and stored
at room temperature, then:

a) What concentration will
remain after 18 months?

b) What is the half-life of the
drug?
C0 = 1% w/v = 1 g/100 mL OR 1000 mg/100 mL = 10
mg/mL

18 months 1 year = 1.5 years 12 months

C = C0 - kt

C = 10 mg/mL - (0.05 mg/mL/year)(1.5 year) = 9.9
mg/mL

b) What is the half-life of the drug?

t1/2 = 0.5C0 = 0.5 (10) = 100 years k 0.05

A colorless 10% aqueous
solution of sodium
sulfacetamide was brought
back to the pharmacist
because it turned yellowish
brown.

a) What can cause this color
formation?

b) What can be done to
prevent similar things from
happening in the future?
Oxidative degradation

Approaches include the following:

i. Use airtight container

ii. Include antioxidant(s) and chelating agent(s) in
the formulation

iii. Protect the formulation from light
9. An ophthalmic solution has a
shelf-life of 6 hours at room
temperature (25oC). What
would

be the estimated shelf-life if
stored in a refrigerator (5oC)?
t90 at 5oC: ?

t90 at 25oC: 6 hours

t90 (at 5oC) = 6 hours = 6 hours = 54 hours 35-25/10
3-2

0. Describe methods to
prevent hydrolytic
degradation, oxidative
decomposition, and

photolytic degradation.
Methods to reduce/prevent hydrolytic degradation:

a) Formulate at the pH of maximum stability Buffers
are used

b) Replace a part or the entire amount of water in
the formulation by non-aqueous solvents, such as
alcohol, glycerin, and propylene glycol

c) Formulate the drug as solid dosage form (e.g.,
tablet, capsule) or as powder for reconstitution

d) Reduce the amount of water in the formulation
(e.g., formulating a suspension in the place of
solution)

e) Change the chemical structure of the drug, such
as structural modifications

f) Store at recommended refrigerated temperatures

g) Useanappropriatecontainer/closuresystem

Methods to reduce/prevent oxidative degradation:

a) During formulation and storage, remove oxygen
and replace it with inert gas

(e.g., nitrogen)

b) Protect the formulation from light

c) Use antioxidants that react with free radicals and
retard the degradation process

d) May use reducing agents that preferentially
oxidized to prevent the drug from

oxidizing (e.g., sodium metabisulfite, ascorbic acid)

e) Chelating agents that complex heavy metals can
be used to eliminate the

catalytic effect of heavy metals in oxidation (e.g.,
chelating agent EDTA)

Methods to reduce/prevent photolytic degradation:

a)

b)

c)

11. Define a)

b)

Use amber colored and coated containers that can
block the radiation causing degradation


Store in a dark place

Coat the tablet with a polymer film containing UV
absorbers
Define the following terms:

a) Shelf-life

b) Degradation half-life

c) Expiration-date

d) Beyond-usedate
Shelf-life is the period of time during which, if
stored properly, the product is expected to retain
acceptable stability.

Degradation half-life is the time taken for a drug to
degrade to half its concentration.

3

c) Expiration-date is the date given on the
MANUFACTURED product packaging which
represents the end of the shelf life.

d) Beyond-use date is the date beyond which
medications that have been manipulated and/or
repackaged and stored or dispensed in a container
other than the original manufacturer's storage
container should not be used.
12. Which types of tablet
coatings are used to mask the
bitter taste of drugs?
Sugar-coating and film-coating; enteric-coating is
NOT used for this purpose.

3. Using the "Rule of 6", what is
the smallest size that will
produce a filled capsule for the

compounded prescription
below?

Atenolol Verapamil HCl
Lactose

DTD caps #30

Sig: 1 every AM PO

30 mg 75 mg qs

NOTE: Atenolol is available as
50-mg tablets (each tablet
weighs 117 mg). Verapamil HCl
is available as 120-mg tablets
(each tablet weighs 400 mg).
Atenolol: 30 mg/cap x 30 capsules = 900 mg

900 mg/50-mg tablet = 18 tablets needed

Each tablet weighs 117 mg; thus, for 18 tablets, the
total weight is 2,106 mg.

Verapamil HCl: 75 mg/cap x 30 capsules = 2,250 mg

2,250 mg/120-mg tablet = 18.75 tablets needed
(must use 19 tabs)

2,280 mg Drug (in 19 tablets) = 7,600 mg total weight
of 19 tablets

X =

7,500 mg + 2,106 mg = 9,606 mg for 30 capsules;
each capsule = 320.2 mg (drugs)

2,250 mg DRUG needed for Rx X

7,500 mg

Rule of 6:

6 6666 0 2 3 4 5 6 4321

Capsule Size x 65

6 1

5 325

390 260 195 130 65

As a result, one should attempt Capsule Size #1 first.

14. Define the following terms:

a) Levigation

b) Spatulation

c) Pulverization by intervention

d) Trituration

e) Geometric dilution

f) Comminution
a) Levigation is the process of triturating while
moistened with a liquid in which the

powder is INSOLUBLE.

b) Spatulation is the blending of small amounts of
powders by movement of a
spatula through them on a sheet of paper or an
ointment tile.

c) Pulverization by intervention is the process of
reducing and subdividing a

substance by adding an easily removable solvent.

d) Trituration is the process of grinding a drug to
reduce its particle size. Trituration

also means to mix/blend (depending on the context
in which it is used) powder.

e) Geometric dilution is a mixing method intended
to ensure homogenous drug

distribution.

f) Comminution is the reduction of the particle size
of a solid substance into a finer

state.
15. What is the percentage
strength of a trituration
containing 120 mg of hyoscine
with 2.28 g of lactose?
0.120 g x 100 = 5% (0.120 g + 2.28 g)
16. What is the difference
between the rate and the rate
constant of a reaction?
The RATE of a reaction/process is the speed or
velocity at which the reaction/process occurs. The
RATE CONSTANT is the measure of the actual rate
of the reaction. For example, a large rate constant
(k) indicates a fast reaction/process.

17. How do the rates of the
first-order and zero-order
reactions change with time?
In a FIRST-ORDER process, the AMOUNT of drug
lost in a certain time interval decreases as the
reaction proceeds, whereas in a ZERO-ORDER
process, the AMOUNT of drug removed in the time
interval remains CONSTANT.
18. How is the graph of
concentration versus time
different for first-order and
zero-order
reactions?
For a ZERO-ORDER process, a plot of C
(concentration) against t (time) gives a straight line.
A linear plot confirms that the process follows
ZERO-ORDER process. For a FIRST-ORDER
process, a plot of lnC against t (time) creates a
straight line.
What are the units of zero-
order and first-order rate
constants?
ZERO-ORDER: concentration/time

FIRST-ORDER: 1/time or time-1
What is meant by the
decomposition half-life of a
reaction or process?

What type of graph will give a
straight line for a zero-order
reaction?

What type of graph will give a
straight line for a first-order
reaction?
The time taken for amount or concentration of drug
to decrease by one half.

C (concentration) against t (time)

lnC against t (time)
How do rates of chemical
reactions change with
temperature?
Generally speaking, for pharmaceutical reactions:

As temperature increases, there are more collisions
between reactant molecules. The result is a faster
rate of reaction and a larger rate constant.

22. Curve III represents a(n) ____
tablet formulation.
extended release
23. Only tablets, each
containing 50-mg of
hydrochlorothiazide, are
available. How many tablets
should be used to obtain the
amount of hydrochlorothiazide
needed to prepare the
prescription below?

Hydrochlorothiazide 20 mg

Triamterene Lactose qs

M. et. DTD caps #15 Sig: i cap
bid, UD

40 mg
Hydrochlorothiazide: 20 mg/cap x 15 caps = 300 mg

300 mg HCTZ is required for making 15 capsules;
thus 300 mg/50-mg HCTZ tablet = 6 tablets needed
24. A 200 mg/mL drug
suspension degrades by zero-
order kinetics. The
concentration after 6 months is
195 mg/mL.

a) What is the zero-order rate
constant?

b) What will be the
concentration of the
suspension after 2 years?

c) How long will it take for the
concentration to decrease to
150 mg/mL?
..C = C0 - kt

195 mg/mL = 200 mg/mL - k(6 months) k = 0.83
mg/mL/month.

2 years = 24 months

C = 200 mg/mL - 0.83 mg/mL/month (24 months) C
= 180.1 mg/mL

150 mg/mL = 200 mg/mL - 0.83 mg/mL/month (t) t =
60.2 months

25. Describe the role of the
stomach and small intestines in
oral drug absorption. Why are
most drugs absorbed from the
small intestines?
a) Stomach: Grind up a solid dosage form and
facilitate release and dissolution for subsequent
absorption from the small intestines

passive transcellular absorption could occur given
sufficient time; however, the stomach plays a
negligible role in the absorption of most drugs
under normal circumstances

b) Intestines: Most important region for absorption
of orally administered drugs

As a result of surface area (large surface area) and
residence time, the small intestines

are the main site for drug absorption.
26. How do most drugs cross
epithelial barriers?
Passive transport (passive transcellular diffusion)

7. What is meant by the shelf-
life of a drug product? Discuss
the various aspects of stability
of a drug product.
The shelf-life is the time period after initial
manufacture for which the drug concentration
remains within limits (e.g., currently, the accepted
limit of chemical decomposition for most drug
products is 10% [maximum]). The major types of
stability that are of concern in a drug product are:

a) Chemical stability - refers to the change in
concentration or amount of the active ingredient in
the product with time

The drug in a drug product can degrade with time
as a result of chemical reactions, such as hydrolysis,
oxidation or photolysis. This results in a DECREASE
in the amount of drug in the dosage form, therefore,
a decrease in the dose provided to the patient.

Hydrolysis is probably the most significant reaction
for chemical stability of drugs. This is because many
drugs have functional groups (e.g., ester, amide,
lactone, lactam) that are prone to hydrolytic attack.

b) Physical stability - physical characteristics of
dosage forms change with time (e.g., dissolution
rate, uniformity, appearance, taste, and odor)

These changes influence effectiveness, safety, and
reliability of the product.

c) Microbiological stability - a measure of its
resistance to microbial contamination from the
environment during storage and use

Microbial growth is likely in products with high
moisture content (e.g., solutions, dispersions, and
water-based semisolids)

Contamination and subsequent growth of microbes
can compromise the safety of a drug product
28. Explain how you would mix
200 mg of Drug A with 1400
mg of Drug B.
Use geometric dilution..

29. In nearly all compounding
situations, what must a
pharmacist do to a powder?
Reduce the particle size
30. List five advantages that
solid dosage forms have over
liquids.
a) Drugs and chemicals are most stable as dry
solids.

b) Because they are dry and compact, solid dosage
forms are packaged,

transported, administered, and stored more easily
than are liquids.

c) Undesirable taste is more noticeable when
substances are in solution than when

in solid form.

d) Accurate dosing is easier to achieve with dosage
forms furnished as individual

units, such as tablets, divided powders, and
capsules.

e) Controlled release is much easier to achieve with
solid dosage forms than with

liquids.
31. The first-order rate constant
for the hydrolysis of aspirin at
pH 7 and 25°C is 0.013 hr-1.

a) If you make a 1 mg/mL
solution of aspirin at pH 7 and
25°C, what will its
a. lnC = lnC0 - kt

lnC = ln1 - 0.013(24) lnC = -0.312

C = 0.73 mg/mL

b. t90 = 0.105 = 0.105 = 8.1 hours k 0.013

The half-life for a solution of
acetaminophen at pH 2 and
25°C is 0.8 year. Assume that
the reaction follows first-order
kinetics.

a) What is the first-order rate
constant of the reaction?

b) How long will it take for the
concentration of a 10 mg/mL
solution of acetaminophen

at pH 2 and 25°C to drop to
80% of its initial concentration?
a. t1/2 = 0.693

k

k = 0.693 = 0.87 year-1

0.8
b. C = 0.80 x 10 = 8 mg/mL lnC = lnC0 - kt

ln8 = ln10 - 0.87(t)

t = 0.26 year
When is it appropriate to use
nonoral routes for systemic
delivery?
.It is not possible to administer a drug orally if its
properties or the patient characteristics are
unfavorable or inappropriate. Examples include, but
not limited to, the following:

a) Instability in GI fluids and consequent rapid
degradation (drug characteristics)

b) Irritation of the gastric or intestinal epithelium
(drug characteristics)

c) Needs immediate response; not provided by
relatively slow oral absorption

d) Suffering from GI distress (patient characteristics)

e) Unable or unwilling to swallow medications
(patient characteristics)..

When are sustained-release
products a better therapeutic
option? What are the
differences

between immediate-release
and sustained-release
products?
The goal for most conventional dosage forms (or
conventional drug delivery systems) is rapid
dissolution of drug after administration. These are
immediate-release systems. The objective with these
systems is to get the drug into the bloodstream and
to the site of action as rapidly as possible. With each
dose of an immediate-release product, the
concentration of drug in the bloodstream rises
rapidly, peaks very soon after administration, and
then declines. If the peak concentration is too high,
then the drug may exhibit undesirable side effects.
If the decline in blood concentration is very rapid,
then the product may have to be dose very
frequently to maintain therapeutic blood levels.
Such a large fluctuation in blood concentration may
not be suitable for some drugs. For modified-
release dosage forms (particularly controlled-
release systems), the primary objective is to achieve
a therapeutic drug concentration at the site of
action for the desired duration of time. For
controlled-release formulations, a degree of
predictability and reproducibility in drug dissolution
from the dosage form is

expected. Major benefits of these systems include
less frequent dosing, improved pharmacokinetics
(less fluctuation of drug concentration in the blood)
and pharmacodynamics (better efficacy and fewer
side effects), and better patient compliance.

Not all drugs can or should be formulated in
modified-release formulations (e.g., sustained-
release systems). The physicochemical properties of
the drug may make modified-release (e.g., sustained
release) delivery unfeasible. In addition, constant
blood levels may not be pharmacodynamically or
therapeutically desirable for some drugs or disease
states.

.
Definethefollowingdosageforms:

a) Powders

b) Granules

c) Capsules

d) Tablets

e) Pills

f) Lozenges

g) Medication sticks

h) Molded tablets

i) Insufflations

j) Dentifrices
a) Powders - mixture of finely divided drugs

b) Granules - prepared agglomerates of powdered
materials

c) Capsules - describe a package made from gelatin
or other suitable material,

which is filled with medicines to produce a dosage

d) Tablets - solid dosage forms prepared with or
without suitable pharmaceutical

excipients

e) Pills - small spherical or ovoid solid dosage forms
containing a medicinal agent

in a matrix

f) Lozenges - solid preparations, which are intended
to dissolve or disintegrate

slowly in the mouth

g) Medication sticks - dosage form for the topical
delivery of drugs

h) Molded tablets - tablets prepared by molding
rather than by compression

i) Insufflations - powders intended for application to
the body cavities

j) Dentifrices - powders used to clean the teeth
What is the largest capsule size
used orally in humans?
Usually 00 (double zero)
Hard shell capsules are made
from what substance?
Usually gelatin
Why must a certain percentage
of water be present in hard
shell capsules?
Lack of adequate moisture in shells causes them to
be hard and brittle, which makes them difficult to
work with and this may affect their dissolution and
bioavailability

Show all calculations and write
your procedure, in step-by-
step detail, for weighing 20 mg

of codeine for a prescription
using a standard Class III
torsion balance. Use lactose as
your

diluent.
20 mg of codeine is needed

For the Class III (A) balance, the least weighable
quantity (LWQ) is 130 mg.

130 mg Codeine Weighed = X

X =

845 mg is the total mixture (130 mg Codeine and
715 mg lactose)

Procedure:

a) Weigh130mgcodeine

b) Weigh 715 mg lactose

c) Mix codeine and lactose (from Parts A and B
above) using geometric dilution

d) Weigh 130 mg aliquot from the mixture in Part C
above. This 130 mg-aliquot

contains 20 mg of codeine (amount needed for Rx)
The presence of what chemical
component(s) distinguishes
soft shell capsules from hard

shell capsules?
Plasticizers (e.g., glycerin and/or sorbitol)
What guideline, or general rule,
is suggested in assigning
beyond-use dates to

extemporaneously
compounded capsules
containing stable powders?
he beyond use date is not later than the time
remaining until the earliest expiration date of any
API or 6 months, whichever is earlier.

An aesthetic appearance to the
final product is always
required. What is one way you
can

keep fingerprints off of the
capsule shells during
compounding
Use gloves or fingercots.
When ethyl alcohol is used as a
preservative, what
concentration range should be
used?
15-18%

Why are density calculations
and mold calibration so
important when compounding

lozenges using the fusion
method?
Lozenges are generally made from solid ingredients
and drugs which are measured by weight. When
they are mixed, melted, and poured into mold
cavities, they occupy a volume, i.e., the volume of
the mold cavity. Since the components are
measured by weight but compounded by volume,
density calculations and mold calibration are
required to provide accurate doses.

When a drug is placed in a base, it will displace an
amount of base as a function of its density. If the
drug has the same density as the base, it will
displace an equivalent weight of the base. If the
density of the drug is greater than that of the base,
it will displace a proportionally smaller weight of
the base.

In other words, this is because each formulation will
have a different density. When compounding
lozenges, the volume occupied by the various
ingredients MUST be determined. This is due to the
differences in densities of the ingredients. As a
result, different substances will occupy different
volumes in the molds.
Why does a drug need to have
both hydrophilic and lipophilic
properties?
A drug has to be compatible with both aqueous and
lipid environments. The ability of a drug to dissolve
in a lipid phase when an aqueous phase is present is
important because it mimics typical situations found
in the body.

List reasons for the
incorporation of drugs into
SOLID dosage forms.
There are many reasons for the incorporation of
drugs into solid dosage forms. See Lecture/Text for
a detailed explanation. Some major reasons include:
a) For accuracy and convenience of dosing; b)
Protection of a drug substance from destructive
influences of atmospheric oxygen or humidity; and
c) Protection from influence of gastric acid after
oral administration.
Describe the importance of a
drug's powder particle size.
See Lecture/Text for a detailed discussion. The
following points briefly answer the question:

The particle size of a drug can affect its release
from dosage forms that are administered.

The successful formulation of tablets and others
dosage forms also depends on the particle size
achieved in the product.

In the area of tablet and capsule manufacture,
control of the particle size is essential in achieving
the necessary flow properties and proper mixing of
granules and powders.

Particle size affects the dissolution
Describe the excipients used in
the formulation and
manufacture of capsules AND
tablets.
Capsule and tablet formulations may include the
following excipients:

a) Diluents, which give plug-forming properties

b) Lubricants, which reduce powder-to-metal
adhesion

c) Glidants, which improve powder flow

d) Wetting agents, which improve water penetration

e) Disintegrants, which produce disruption of the
powder mass

f) Coloring agent

g) Coating agent

h) Sweetening agent

What are the qualities of a
good tablet?
Some include the following:

a) Freeofdefects

b) Accurate & uniform weight

c) Homogeneity

d) Absenceofincompatibilities

e) Stability & hardness

f) Ease of disintegration

g) Reasonable size and shape

h) Pleasing appearance
What are the basic steps
involved in wet granulation and
direct compression processes?
When is direct compression the
preferred method for
preparing tablets?
Direct compression is less complex (thus is
preferred). However, this method is

applicable to materials that possess cohesive and
flow properties.
Define and differentiate weight
variation from content
uniformity. What are the USP
requirements for oral
immediate-release tablets AND
capsules?
Weight variation measures the variability in the
amount of powder contained in each dosage unit
(e.g., capsule, tablet). Content uniformity measures
the variability in the amount of active drug
contained in each dosage unit. It is POSSIBLE to
pass weight variation requirement but fail the
content uniformity requirement due to the fact that
the drug content is not uniformly distributed
through all the dosage units.

USP requirements:

Meet content uniformity requirement if the amount
of active ingredient in

dosage unit is within 85-115% of the label claim

What are some characteristics
of drugs that make them good
candidates for delivery in an
extended-release oral
formulation?
a) The drug should have high potency and should
be administered in a small dose (e.g., less than 1000
mg).

b) The drug substance should exhibit a half-life of
between 2-8 hours.

c) The drug should possess a good margin of safety.

d) The drug should exhibit neither very slow nor
very fast rates of absorption and

excretion.

e) The drug must be uniformly absorbed from the GI
tract (e.g., passive transport).

f) The drug substance is used for the treatment of
chronic rather than acute

conditions.
List reasons for carrying out
dissolution studies.
Guide formulation and product development

b) Assess bioequivalence between various
formulations

c) Requirement for regulatory approval of marketing
for products
Briefly describe the following
drug delivery technologies or
platforms:

a) Microspheres

b) Liposomes
a) Microspheres serve as drug delivery carriers. A
method to produce microspheres

is the microencapsulation technology, which is a
process by which the drug is enclosed in
microscopic particles by formation of thin coatings
of wall material (e.g., gelatin, albumin) around the
drug substance.

b) Liposomes are composed of small vesicles of a
bilayer of phospholipid encapsulating an aqueous
space. They serve as drug delivery carriers.

How can we tell whether a
drug is likely to be susceptible
to hydrolytic degradation

(hydrolysis)?
If the drug contains one of the following functional
groups: Ester, amide, lactone, or

lactam.
The expiration date on a
pharmaceutical product states
"Expires December 2012." This

means that by that expiration
date, the product may have
lost: ________________________.
...ufficient activity to be outside USP requirements
(currently, the standard is NOT more than 10%;
however, this could change over time as well as
there might be different standards for some specific
drug products).
Why is granulation normally a
part of manufacturing tablets?
Granules flow well compared to powders.
Granulations are commonly used in

tablet making to facilitate the free flow of material
from the hopper (feeding

container) into the tablet presses.

b) Additionally, compaction characteristics of the
mixture are improved as a result

of granulation.

c) The surface area of granules is less than that of a
comparable volume of powder,

thus granules are more stable to the effects of
humidity and are less likely to cake or harden upon
standing.

What is USP Chapter <795>?
Why should compounders be
familiar with it?
Pharmaceutical Compounding - Nonsterile
Preparations

United States Pharmacopeia (USP) establishes
standards for the quality, purity, identity, and
strength of medicines, food ingredients, and dietary
supplements. As a result, compounders must be
familiar with the standards for pharmaceutical
compounding. The standards are enforceable by
governmental agencies.

or each of the following
dosage forms, explain what it is
and describe its

disintegration/dissolution rate.

a) Molded tablets

b) Plain tablets

c) Chewable tablets

d) Enteric-coated tablets

e) Rapidly disintegrating tablets

f) Lozenges

g) Immediate-releasetablets

h) Bilayer tablets

i) Buccal tablets

j) Sublingual tablet
a) Molded tablets - tablets prepared by molding
rather than by compression; rapid dissolution

b) Plain tablets - dosage forms that are designed to
disintegrate and release their medication with no
special rate-controlling features

c) Chewable tablets - tablets have a smooth, rapid
disintegration when chewed or allowed to dissolve
in the mouth; useful for administration of large
tablets to children and adults

d) Enteric-coated tablets - tablets designed with
delayed release features; dosage form pass
unchanged through the stomach to the intestines

e) Rapidly disintegrating tablets - tablets
characterized by disintegrating in the mouth within 1
minute, some within 10 seconds

f) Lozenges - solid preparations, which are intended
to dissolve or disintegrate slowly in the mouth

g) Immediate-release tablets - dosage forms that
are designed to disintegrate and release their
medication with no special rate-controlling features

h) Bilayer tablets - layered tablet prepared by initial
compression of fill material in a die followed by
additional fill material & compression to form bi-
layered tablets; bilayer tablets may be designed for
staged drug release

i) Buccal tablets - tablets intended to be dissolved
in the buccal pouch for absorption through the oral
mucosa; erode slowly

j) Sublingual tablet - tablets intended to be
dissolved beneath the tongue for absorption
through the oral mucosa; dissolve promptly

A prescription balance has a
sensitivity requirement of
0.0065 gram. Explain how you
would weigh 0.020 gram of
atropine sulfate with an error
not greater than 5%, using
lactose as the diluent.
Sensitivity Requirement (mg) x 100 = Least
Weighable Quantity (mg)

% Error

6.5 mg x 100 = X 5

X = 130 mg (LWQ)

ALIQUOT METHOD/TRITURATION:

130 mg Atropine Sulfate (stock bottle) = 20 mg
Atropine Sulfate (needed for Rx) X mg Mixture 130
mg Aliquot

X = 845 mg (130 mg drug + 715 mg lactose)

*One may select a different amount; however,
remember that the LWQ is 130 mg. As a result, the
amount must be at least 130 mg.

Procedure:

1. Weigh 130 mg drug and 715 mg lactose.

2. Triturate powders using geometric dilution.

3. From the mixture in Step #2, weigh out 130 mg
aliquot. This 130-mg aliquot

contains 20 mg of atropine sulfate needed for
compounding the prescription.

Calculate the amounts required
to compound the following
prescription. Assume that you
are using a Class III
prescription balance with a
sensitivity requirement of 6.5
mg and at least 95% accuracy
(5% error) is required.
Sensitivity Requirement (mg) x 100 = Least
Weighable Quantity (mg) % Error

6.5 mg x 100 = 130 mg 5

Carbamazepine: 30 mg/packet x 8 packets = 240
mg. The amount required for the prescription is
greater than the LWQ; as a result, the aliquot
method is NOT required.

Lactose: The total amount of powder mixture per
packet is 300 mg, thus 300 mg -

30 mg Carbamazepine = 270 mg lactose/packet. We
need 8 packets, thus 270 mg/packet x 8 packets =
2,160 mg lactose. OR, (300 mg/packet x 8 packets) -
240 mg Carbamazepine = 2,160 mg Lactose.

To compound this prescription, weigh out 240 mg
of drug and 2,160 mg of lactose and

triturate using geometric dilution.

62. Definethefollowingterms:

a) Glidant

b) Lubricant

c) Wetting agent

d) Stabilizer

e) Disintegrant

f) Binder

g) Filler
a) Glidant - ingredient in a formulation that allows
particles moving smoothly,

continuously and effortlessly

b) Lubricant - ingredient in a formulation that is
capable of reducing or preventing

friction, heat, and wear when introduced as a film
between solid surfaces

c) Wetting agent - a surfactant which allows easy
spreading of water on the surface

d) Stabilizer - ingredient in a formulation that
improves product stability

e) Disintegrant - ingredient in a formulation that
promotes breakup of the tablets

after administration

f) Binder - ingredient in a formulation that promotes
adhesion of the particles

g) Filler - is added to increase the bulk of the
formulation
What is the (usually) largest
capsule size used orally in
humans?
00 (double zero)
Patients who can not swallow
modified-release (e.g., enteric-
coated, sustained-release,

controlled-release) capsules
should:
____________________________________________
ld consult a pharmacist for an alternative product.
Modified-release products should NOT be
manipulated.

Indicate a possible use
(purpose) of each of the
following ingredients in a
capsule formulation:

Diphenhydramine HCl 10%
Microcrystalline cellulose 25%

Lactose 62.5%

Croscarmellose sodium 2%

Colloidal silicon dioxide 0.2%
Magnesium stearate 0.3%

66. What is meant by the
partition coefficient of a
compound? What is the
approximate range of
desirable logP values for a
drug?

67. Discuss the mathematical
expression describing the
dissolution of a solid drug
particle. What parameters can
be changed to increase or
decrease dissolution rate?

68. The rate of absorption of a
drug can be described by the
__________________ equation. Explain
the parameters of the
equation.

69. Describe the significance
and impact of the first-pass
effect after oral administration.

70. Briefly describe the
sublingual route of
administration, giving
advantages and disadvantages

Antihistamine Diluent/filler Diluent/filler
Disintegrating agent Glidant

Lubricant

of the method.

71. Briefly describe the oral
route of administration, giving
of the

method.

72. In nearly all compounding

73. Why is it desirable for
powders intended for internal
use to be in a fine state of
subdivision?

74. What is the
biopharmaceutics classification
system?

between extended-release,
delayed-release, sustained-
release,

modified-release, and
controlled-release?

between systemic and local
administration of drugs?

77. What are rate-limiting steps
for the oral absorption of a
solid drug product?

78. List major reasons for
coating tablets.

79. List the FDA requirements
for bioequivalence for a
generic drug.

80. List the FDA requirements
for generic drugs.

6

What is meant by the partition
coefficient of a compound?
What is the approximate range
of desirable logP values for a
drug?
The partition coefficient (P) is the balance between
lipophilicity and hydrophilicity of a compound in its
unionized form. Determination of P involves placing
a lipid solvent and an aqueous solvent in contact
with each other and adding the compound of
interest to this solvent system. Molecules of the
compound will distribute between the two
immiscible solvents or phases. P = [Lipid solvent
(e.g., octanol)] / [Aqueous solvent (e.g., Water)]. If
the compound is more hydrophilic than lipophilic,
its concentration in water will be higher. In other
words, the partition coefficient provides a measure
of the relative affinity of a compound for lipid and
aqueous phases. A compound with P = 1 has equal
affinities for lipid and water. A P value greater than
one implies that the compound is lipophilic.
Partition coefficient is often stated as a logarithmic
(log P) value for convenience. A compound with
logP < 0 is usually considered too hydrophilic to be
a suitable drug candidate. Keep in mind that it
needs to cross lipophilic biological membranes for
its activity. On the other hand, compounds with logP
> 3.5 are usually too lipophilic to be good drugs
because they tend to be poorly water soluble. Thus,
a compound has to have a balance of hydrophilic
and lipophilic properties for it to be a successful
drug.

Discuss the mathematical
expression describing the
dissolution of a solid drug
particle. What parameters can
be changed to increase or
decrease dissolution rate?
The dissolution rate of a drug is given by the
modified Noyes-Whitney equation, derived from
Fick's first law of diffusion:

Dissolution rate = D x A (S-C) h

D = Diffusion coefficient

A = Surface area

(S-C) = Concentration gradient

h = Thickness of the diffusion layer

The diffusion coefficient is a coefficient that
measures how well a solute (e.g., drug) can diffuse
in a particular medium. It is defined as the rate at
which a diffusing solute is transported between two
regions where there is a unit concentration gradient
between them. The diffusion coefficient depends on
size (or molecular weight) of the molecule, the
medium in which it is diffusing, and temperature. The
larger the molecular weight, the lower the diffusion
coefficient.
The rate of absorption of a
drug can be described by the
__________________ equation. Explain
the parameters of the
equation.
equation for the rate of absorption is similar to Fick's
law of diffusion:

Absorption rate: P x A x D x (Ca-Cp) h

P = Partition coefficient

A = Surface area of membrane D = Diffusion
coefficient

Ca-Cp = Concentration gradient h = Thickness

The partition coefficient (P) and diffusion coefficient
(D) depend on the structure of the drug. H is the
thickness of the membrane at the absorption site;
this membrane may be composed of one or several
layers of cells.

Describe the significance and
impact of the first-pass effect
after oral administration.
After oral administration, all of the drugs must pass
through the liver before reaching systemic
circulation. This results in exposure of the drug to
drug-metabolizing enzymes prior to the drug
reaching systemic circulation. The intestinal wall can
also represent a site of first-pass metabolism. This is
sometimes referred to as pre-systemic elimination.
The consequence of the first-pass effect is that the
fraction of drug reaching systemic circulation is
substantially reduced. Drugs (e.g., lidocaine) that are
extensively metabolized by the liver may not be
given orally.
Briefly describe the sublingual
route of administration, giving

of the method.
The sublingual route of administration is the delivery
of drug into the blood through tissues under the
tongue. Some advantages and disadvantages are
given below:

Advantages:

- Rapid onset

- Convenient

- Avoids first-pass effect

Disadvantages:

- Few drugs are adequately absorbed through this
route

- Compliance is difficult

**For sublingual administration, the onset is rapid
and the duration is short. For buccal
administration, which is the administration of drug
through the mucosal membranes lining the
cheeks, the onset can be rapid, but the duration is
long.**

Briefly describe the oral route
of administration, giving
of the

method.
This route is where a drug product is administered
by mouth and swallowed. It is effective if the drug is
able to cross the epithelial membranes of the GI
tract efficiently. Some advantages and
disadvantages are given below:

Advantages:

- Convenient - Economical - Noninvasive

Disadvantages:

- Destruction of drugs by gastric acid and digestive
juices

- First-pass effect
In nearly all compounding
Reduce the particle size
Why is it desirable for powders
intended for internal use to be
in a fine state of subdivision?
The rate of dissolution and therefore often the
bioavailability of the drug depend on

the particle size of the drug.
What is the biopharmaceutics
classification system?
The BCS system is a scientific framework for
classifying orally administered drugs on the basis of
their aqueous solubility and intestinal permeability.
The BCS takes into account three major factors that
govern the rate and extent of drug absorption from
solid oral drug products: Dissolution, solubility, and
intestinal permeability.

What is the difference between
extended-release, delayed-
release, sustained-release,

modified-release, and
controlled-release?
Modified-release
- Dosage forms having drug release features based
on time, course, and/or

location that are designed to accomplish
therapeutic or convenience

objectives not offered by conventional or
immediate-release forms • Extended-release (ER)

- One that allows a reduction in dosing frequency to
that presented by a conventional dosage form

• Delayed-release

- Designed to release the drug from the dosage
form at a time other than

promptly after administration

- Delay may be time based or based on the
influence of the environmental

conditions

• Controlled-release

- Delivery of drug at a pre-determined rate. This is a
type of extended- release.

• Sustained-release

- This is a type of extended-release. With sustained-
release, the delivery of

the drug is NOT at a pre-determined rate (not
constant).
What is the difference between
systemic and local
administration of drugs?
Systemic administration - Entrance of the drug into
the circulatory system and transport to the cellular
site of its action

• Local administration - Direct application of the
drug to the desired site of action
What are rate-limiting steps for
the oral absorption of a solid
drug product?
Disintegration is potentially the first rate-limiting
process when a solid dosage form is

administered; however, frequently, DISSOLUTION is
the rate-limiting step.

List major reasons for coating
tablets.
Major reasons include, but not limited to, the
following:

Taste masking

Improve ingestion

Improve appearance

Ease of identification

Protect active ingredients from the environment

For specialized purposes, such as controlling drug
release in the GI tract (e.g.,

enteric coating)
List the FDA requirements for
bioequivalence for a generic
drug.
If the mean values of AUC and Cmax for two
products are within 80% to 125% of each

other, then the two products are considered
bioequivalent.
List the FDA requirements for
generic drugs.
Contain the same active ingredient(s)

Be identical in strength, dosage form, and route of
administration

Have the same indications and precautions for use
and other labeling

instructions

Be bioequivalent

Meet same batch-to-batch requirements for
identity, strength, purity, and

quality

Is manufactured under the same strict standards of
FDA's Current Good

Manufacturing Practice regulations as required for
pioneer products

How many grams of pure
hydrocortisone powder must
be mixed with 60 g of 0.5%
hydrocortisone cream if one
wishes to prepare a 2.0%
preparation?
Alligation

0.5 98 parts of 0.5% ointment

100 1.5 parts of pure (100%) zinc oxide

98 parts of 0.5% ointment = 60 g of 0.5% ointment
1.5 parts of pure zinc oxide X

X = 0.92 g of pure zinc oxide

Algebra

(0.5%)(60 g) + (100%)(X) = (2%)(60 g + X) 30 g + 100X
= 120 g + 2X

98X = 90 g

X = 0.92 g of pure zinc oxide
How many grams of 1%
hydrocortisone cream must be
mixed with 0.5%
hydrocortisone cream if one
wishes to prepare 60 g of a
0.8% w/w preparation?
Alligation

1 0.3 0.5 0.2
parts of 1% cream

0.8
parts of 0.5% cream 0.5 PARTS TOTAL

0.3 parts of 1% cream = X g of 1% cream 0.5 parts
TOTAL 60 g TOTAL

X = 36 g of 1% cream

Algebra

(1%)(X) + (0.5%)(60 g - X) = (0.8%)(60 g) 1X + 30 g -
0.5X = 48 g

0.5X + 30 g = 48 g 0.5X = 18 g

X = 36 g (of 1% hydrocortisone cream)
Calculate the amount of
calamine in 10 g of a 10% w/w
calamine ointment.
(10 g Calamine) x 10 g Ointment = 1.0 g Calamine

100 g Ointment
Sugar-coating relies primarily
on the use of:
___________________________________.
sucrose.

Which is the most important
mechanism responsible for
(most) drug degradation?
Hydrolysis
The shells of soft gelatin
capsules may be made elastic
or plastic-like by the addition
of: __.
plasticizer(s), such as glycerin and/or sorbitol.
Molded tablets are generally
prepared by mixing the drug
substance with ___________ that
serves as the base.
lactose
What are potential adverse
effects of instability in
pharmaceutical products?
a) Loss of active ingredient

b) Alterationofbioavailability

c) A toxic product may be formed
A product label indicates
storage in a "cold" place. What
is most appropriate storage

location for the drug product?
.tion for the drug product?

• Any temperature NOT exceeding 8oC

- Refrigerator: 2o - 8oC

- Freezer: (minus)-25o - (minus)-10oC..
The drug release from oral
osmotic controlled-release
systems is affected by: ___________.
osmotic

pressure in the gastrointestinal tract.
What factors are usually
included in accelerated
stability studies?
emperature, light,

humidity, and pH

The main objective(s) of
dosage form design is(are) to
ensure: _______________________.
a) Reproducible product quality

b) Useracceptability

c) Accuracy and convenience of dosing
What studies are required for
approval of generic drug
products?
Bioequivalence studies (e.g., study in a small group
of healthy volunteers)
What are the reasons for poor
bioavailability of a drug after
oral administration?
Drug degradation in the GI tract; first-pass
metabolism
Why are the parameters Cmax,
tmax, and AUC usually
acceptable for providing that
the two drug products are
bioequivalent?
These parameters provide relevant information
regarding the bioavailability of the drug products.
Cmax and AUC are measures of the extent of drug
absorption, and Tmax and Cmax are measures of
the rate of drug absorption.

Pharmaceutical Sci Flashcards _ Quizlet.pdf

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