Lab 5

Question 1

many formulation issues can be solved by what 2 things?

Answer 1

the careful selection of excipients and the use of good techniques

Question 2

name 3 suspending agents.
are they hydrophobic or hydrophilic?

Answer 2

methylcellulose (MC)
carboxymethylcellulose (CMC)
natural gums (tragacanth)

EXTREMELY HYDROPHOBIC COMPOUNDS

Question 3

methylcellulose, carboxymethlcellulose, and natural gums (tragacanth) are suspending agents.
what is another term for them?

Answer 3

hydrocolloids

Question 4

since MC, CMC, and tragacanth are extremely hydrophobic compounds, what is an important consideration when working with them?

Answer 4

they form lumps when added directly to water (fish eyes)

they are difficult to break up and slow to dissolve because the water does not penetrate beyond the hydrated surface

Question 5

explain the structure of the lumps/fish eyes formed from the addition of extremely hydrophobic suspending agents directly to water

Answer 5

they consist of a swollen hydrated gel at the surface and a dry core at the center

Question 6

___ and ____ are amphiphilic molecules containing polar and nonpolar moeities in their structure

Answer 6

glycerin and ethanol

Question 7

true or false

glycerin and ethanol, because they are amphiphilic, can interact favorably with hydrophilic and hydrophobic drugs

Answer 7

true

Question 8

glycerin and ethanol have ______ capacity

Answer 8

wetting

Question 9

besides their wetting capacity, glycerin and ethanol can act as ______ for hydrocolloids

Answer 9

dispersants

Question 10

name a common technique to prepare suspension vehicles when using hydrocolloids

name 2 other techniques

Answer 10

make a slurry of the hydrocolloid with glycerin or ethanol and then carefully add water to the slurry with stirring

the glycerin/ethanol forms a coat around the dry particles, delays the surface swelling, and even permits hydration

another method is to have the hydrocolloidal suspending agent mixed with water and kept standing for several hours before dissolving with the aid of heat

another is to vigorously agitate the water and the suspending agent is sprinkled carefully in the vortex (formed with the water) to ensure the quick dispersion of the particles

Question 11

explain the vigorous agitation method of preparing suspensions with hydrocolloids further

Answer 11

vigorous agitation may result in foaming.
once dissolved, the colloidal suspension is allowed to stand for at least 24 hours to complete hydration and reach maximum viscosity

Question 12

hydrocolloids

Answer 12

extremely hydrophobic
cellulose derivatives and gum

Question 13

_____ are directly added to water as they do not form the same lumps as the cellulose polymers or gums (tragacanth)

Answer 13

clays (bentonite)

Question 14

as mentioned, clays (bentonite) are added directly to water because they do not form the same lumps as the cellulose polymers and gums.

however….

Answer 14

a period of standing is still required for hydration

Question 15

what is a simple method of preparing suspensions

Answer 15

to dissolve or suspend the drug in simple syrup

Question 16

as mentioned, a simple method of preparing suspensions is to dissolve or suspend the drug in simple syrup.

what is the issue with this?

Answer 16

several drugs have serious stability and compatability issues and the physical, chemical, and microbial stability of the drug must be considered

Question 17

define stability

Answer 17

the extent to which a product retains its labeled content and original properties through its shelf life (period of storage and usage)

Question 18

where are the stability limits specified?
must be at least ______% of the labeled content

Answer 18

in the USP
at least 90%

Question 19

not only must the drug be at least 90% of its labeled content, but also……

Answer 19

the suspension must also retain its desired characteristics such as sedimentation rate, dispersability, flavor, color, etc

Question 20

name 8 factors that alter stability

Answer 20

-pH
-temperature
-light
-humidity
-air (oxygen)
-particle size
-solvents
-other chemicals and contaminants/microbial contamination

Question 21

____ is one of the most important factors affecting the stability of a product

Answer 21

pH

Question 22

drug degradation often occurs via…

Answer 22

pH dependent hydrolysis

Question 23

how is stability determined?

Answer 23

degradation rate constants are calculated for a range of pH values

the degradation rate constants are plotted vs pH to plot a log K-pH profile

Question 24

on the log K-pH profile, the minimum points on the graph are the areas of ____ stability

Answer 24

BEST

Question 25

the pH of the least degradation is used. how is this accomplished?

Answer 25

through use of buffers

Question 26

when adjusting pH with buffers, what is an important consideration

Answer 26

the pH must also be compatible with other excipients and other aesthetic properties of the formulation

Question 27

hydrochlorothiazide is what kind of drug?

Answer 27

a diuretic used to treat hypertension

Question 28

explain how HCTZ (hydrochlorothiazide) accomplishes its function as an antihypertensive agent

Answer 28

it reduces blood volume by increasing the excretion of sodium, water, and potassium. it is also used to treat heart failure and edema in newborns

Question 29

what is the recommended dose of hydrochlorothiazide

Answer 29

1-2mg/kg/dose every 12 hours

Question 30

should HCTZ be taken with meals? any allergy considerations?

Answer 30

should be taken with meals to enhance absorption cross sensitivity may occur in patients allergic to sulfonamide derived drugs

Question 31

explain the physical properties of HCTZ

Answer 31

white (or nearly white) almost odorless, crystalline powder and has a slightly bitter taste aqueous solubility of 722mg/L

Question 32

hydrochlorothiazide oral suspensions prepared using suspending agents (MC, CMC) are shown to produce.....

Answer 32

a flocculated suspension, forming a loosely linked polymer network system that is easily redispersed with mild agitation

Question 33

____ vehicles such as ___ and ___ have been used for extemporaneous HCTZ suspensions from commercial tablets

Answer 33

commercial vehicles such as ora plus and ora sweet

Question 34

what foods should be avoided and/or taken when taking HCTZ?

Answer 34

AVOID: -alcohol -natural licorice -no calcium, aluminum, magnesium, or iron supplements within 2 hours of taking this medication TAKE: -With food -increase potassium intake -- add a banana or orange juice

Question 35

the suspension vehicle when preparing HCTZ suspension should be prepared as required for...

Answer 35

stability and aesthetic characteristics (flavor, color, etc)

Question 36

why should the drug be pulverized when preparing HCTZ suspension?

Answer 36

to achieve the desired particle size

Question 37

pulverization may ____ surface energy and ___ wetting

Answer 37

increase the surface energy and hinder wetting

Question 38

add suitable _____ to form a homogeneous paste

Answer 38

wetting agent

Question 39

in HCTZ suspension preparation, the drug is added to the vehicle with ____ intensity mixing

Answer 39

LOW

Question 40

why is the drug (HCTZ) added to the vehicle with low intensity mixing?

Answer 40

any high energy process will incorporate air into the suspension and promote foaming

Question 41

the _____ of the suspension makes it difficult to remove air bubbles

Answer 41

viscosity

Question 42

frequently, entrapped air from bubbles will affect the accuracy of the ______

Answer 42

volume

Question 43

knowing the _______ will ensure accuracy

Answer 43

specific gravity (density of the final product and adjustment of WEIGHT rather than volume)

Question 44

what pH range is HCTZ stable?

Answer 44

2-4