Chapter 4 - Capsules Flashcards
which have a more predictable absorption mechanism and why - tablets or capsules
capsules bc they are already granules
give the definition of capsules
solid dosage forms in which 1 or more medicinal and/or inert substances are enclosed in a smell shell or container (generally prepared from a suitable form of gelatin)
true or false
an advantage to capsules is that they are tasteless
true – bc the material is enclosed within the shell and does not get in contact with the tongue
which are easier to compound - tablets or capsules
capsules
how is it that capsules are more easily administered than tablets?
because the powder is enclosed within the shell so you don’t have to worry about loose powder
TRUE OR FALSE
compared to other solid dosage forms, the bioavailability of capsules is generally worse
FALSE
generally better
how are capsules useful for clinical trials
to hide the placebo and actual drug – mask what is what
TRUE OR FALSE
capsules allow for physicians to prescribe drug combinations that fit individual requirements
true
ex - can put 5 drugs into 1 capsule
how do capsules offer protection from light?
if opaque – ie: titanium dioxide
name 5 scenarios in which the capsule dosage form is not suitable for the drug
drugs that are soluble salts
drugs that solubilize gelatin
hygroscopic drugs
deliquescent drugs
efflorescent drugs
potential for ________ is a disadvantage of the capsule dosage form
tampering
why are hygroscopic and deliquescent drugs not suitable for the capsule dosage form?
they will change the water content of gelatin
what are the 2 kinds of capsule shells
hard gelatin capsules
soft elastic capsules
between the 2 kinds of capsule shells, which can be made in compounding
hard gelatin can – soft elastic cant
soft elastic capsules normally contain what kind of drug
liquid drug
what are the components of a capsule shell
body (where powder is filled) and cap
the drug to be incorporated into capsules can be:
powder
granulation
liquid
semi-solid mass
pellet mixture
capsule
paste
tablet
HARD gelatin capsules contain how much moisture?
13-16% moisture
define gelatin
a heterogeneous proteinaceous (contains protein) material obtained from ANIMAL COLLAGEN by hydrolytic extraction
what is the significance of the fact that hard gelatin capsules contain 13-16% moisture
do not put hygroscopic materials inside bc it will absorb the water content and the capsule will break if the changes are significant
DO NOT STORE IN BATHROOM
What is the solubility of gelatin in water?
almost insoluble in cold water
soluble in hot water and in warm GI fluids
true or false
gelatin is stable in the air when dry
true
gelatin is prone to……
microbial decomposition when it becomes moist (free water)
TRUE OR FALSE
gelatin is digested and absorbed poorly
FALSE - digested and absorbed well
explain the composition of a empty hard gelatin capsule shell
gelatin
sucrose
sulfur dioxide
water
why is sucrose 1 of the components in an empty hard capsule gelatin shell?
for shell hardness and rigidity
why is sulfur dioxide 1 of the components in an empty hard gelatin capsule shell?
for transparency
why are colorants added to hard gelatin capsule shells?
to make the capsule distinctive
what is added to make capsules opaque? (if desired)
titanium dioxide
name the 4 steps of the automated production mechanism of hard gelatin capsule shells
dipping
drying
trimming
joining
name 3 components of coni-snap
tapered rims
indentations
grooves
what is the purpose of the tapered rims in the coni-snap capsule design?
to avoid telescoping (splitting)
what is the purpose of the indentations in coni-snap
to prevent premature opening – don’t want capsule and body to inadvertently separate
what is the purpose of the grooves in coni-snap capsule design
to lock the 2 capsule parts together
what is another variant of coni-snap design
coni-snap supro
capsule size ranges from…
000-5
human use – 000 is too large so 00-5
true or false
higher capsule number means a smalller amount can go in
true
how many mL can 000 hold?
what about 00?
000 = 1.4 mL
00 = 0.95mL
how many mL can 0 hold?
what about 1?
0 = 0.68
1 = 0.50
how many mL can 2 hold?
what about 3?
0.37
0.30
how many mL can 4 hold?
5?
4 = 0.21mL
5 = 0.13mL
rank the following according to density:
aspirin
quinine sulfate
sodium bicarbonate
most dense = sodium bicarbonate
aspirin
least dense = quinine sulfate
as mentioned, between aspirin, sodium bicarbonate, and quinine sulfate, sodium bicarbonate is the MOST DENSE
therefore, _____ mass is needed for sodium bicarbonate to entirely fill the volume of a capsule than for the other 2 drugs
more mass is needed
TRUE OR FALSE
there are 3 size 5 capsules, each containing different drugs in different amounts.
Drug A - 65mg
Drug B - 130mg
Drug C - 97mg
true or false… the volume of each capsule will be different, with the capsule containing Drug B having the most volume
FALSE
ALL CAPSULES WILL HAVE 0.13mL volume bc all size 5
varying mass numbers are simply due to varying densities.
Drug B is the most dense
how many grams of water can go into a size 2 capsule? (assuming nothing else was added)
0.37mL/0.37 grams
bc density of water is 1, it will be exact amount that a size 2 capsule can hold
true or false
only the density of the API is a concern when determining how much drug is needed to fill a capsule
FALSE
density of diluents as well and other things are a concern
when possible, what size capsule should be used
the smallest size - size 5
not necessary but preferred
true or false
the weight is constant but the volume varies for each capsule
FALSE
VOLUME IS ALWAYS CONSTANT
mass varies
how is the proper volume of a capsule maintained?
normally, the amt of API is constant.
therefore, density is maintained by using DILUENT
for which is weight variation more significant – using 65mg of API or using 130mg API?
weight variation is more significant for 65mg API
true or false
if all of the powder formulation fits into a size 5 capsule, a size 5 capsule must be used
FALSE
it is preferred but not necessary
name the 4 steps of preparing filled hard gelatin capsules
-develop and prepare the formulation and select capsule size
-fill capsule shells
-capsule sealing (optional)
-cleaning and polishing the filled capsules
in the 1st step of preparing filled hard gelatin capsules, name 3 things to consider
1st step = develop and prepare formulation and select capsule size
consider:
-accurate dosage
-good bioavailability
-easy to fill the capsule during production
name 3 diluents commonly used in capsules to produce the proper capsule fill volume
lactose
microcrystalline cellulose
starch
name 2 reasons that companies might want to perform capsule sealing, even tho it is optional
when sealed, they will be tamper proof and leak proof
explain how cleaning and polishing process of the filled capsules is accomplished both in small scale and large scale
small scale - cleaned individually in small numbers by rubbing them with clean gauze or cloth, OR mix with salt or sugar or anything that can create friction
large scale - many capsule filling machines affixed with a cleaning vacuum. this removes any extraneous material from the capsules as they leave this equipment
name 3 components in capsule formulation
API
DILUENTS
GLIDANTS (in manufacturing)
others
name 6 diluents for the capsule dosage form
dicalcium phosphate
kaolin
lactose
modified starch
magnesium carbonate
magnesium oxide
name disadvantages of using dicalcium phosphate as a diluent
it retards (slows) the dissolution rate and is incompatible with tetracyclines (forms a complex)
which capsule diluent(s) are good for eutectic mixtures?
kaolin
magnesium carbonate
magnesium oxide
which capsule diluent is incompatible with acidic drugs and why?
magnesium oxide bc it is alkaline in nature
WHY are kaolin, magnesium carbonate, and magnesium oxide good diluents for eutectic mixtures?
bc they absorb the formed liquid
which capsule diluent is incompatible with amines?
give an example of a class of drug that are amines
lactose
sulfa drugs
name 3 glidants that can be used in the capsule dosage form
silicone dioxide
magnesium stearate
talc
true or false
glidants are really only needed in manufacturing and NOT in the small scale preparation of capsules
true – needed for good flow into the die in manufacturing
explain the issue with using magnesium stearate as a glidant in capsule formulation
it has water proofing characteristics which slows the penetration by GI fluids – this delays drug dissolution and absorption
to solve this issue, a surfactant like SLS is added as a wetting agent to facilitate wetting by the GI fluids to overcome the water proofing issue
which glidant used in capsule formulation has water proofing characteristics?
magnesium stearate
true or false
gelatin capsules are suitable for aqueous liquids
false – unsuitable bc water softens gelatin and distorts the capsules, resulting in leakage of the contents.
true or false
it is REQUIRED to reach the max volume of the capsule size chosen
true – add diluents until max volume is reached
name methods of small scale filling hard capsule shells
hand operated capsule filling machine
punching method
explain how the hand-operated capsule filling machines work
empty capsules in the loader tray and place on top of the filler unit
insert the capsules into the filling unit and remove. lift the top plate to separate the caps and bodies
place powder on the unit and fill the capsule bodies
return top plate to the unit and place the caps on the filled bodies
in small scale filling of hard capsule shells, what % error is allowed?
5%
what is the name of the equipment used to fill hard capsule shells in large scale?
how many capsules can be filled in x amount of time?
Osaka automatic capsule filler
165,000 capsules/hour
true or false
automated capsule filling machines have their own content uniformity test
true
true or false
soft gelatin capsules can be made both in manufacturing and in the pharmacy
FALSE – can only be made in manufacturing and not in lab/pharmacy setting
TRUE OR FALSE
soft gelatin capsules come in a VARIETY of shapes and sizes
true
soft gelatin capsules are most often used for what kind of drugs?
liquid or mixtures of liquid
what are the different routes of administration for soft gelatin capsules?
routes are dependent on…..
routes are dependent on the shape of the capsules
oral, rectal, vaginal, specialty for topical, ophthalmic, otic
besides being used for liquids/mixtures of liquids, what else can soft gelatin capsules be used for?
gels, pastes, powders, etc
further classify which liquids/mixtures of liquids that soft gelatin capsules can be used for
-water immiscible, volatile, and nonvolatile liquids (vegetable oils and aromatic oils)
-water miscible and nonvolatile liquids (polyethylene glycols)
-water miscible and relatively nonvolatile
the shells of soft gelatin capsules are made of….
gelatin + the addition of glycerin or polyhydric alcohol (sorbitol) – gelatin elastic
do soft/hard gelatin capsules contain a preservative?
why or why not?
soft gelatin capsules contain a preservative and hard gelatin capsules do not because soft gelatin capsules contain slightly higher moisture content than hard shell capsules
name the typical preservatives for soft gelatin capsules
methyl and propyl parabens
sorbic acid
what are the compendial requirements for the ADDED SUBSTANCES in capsules? (4)
-harmless in the quantities used
-do not exceed min. amounts required to produce their intended effect
-do not impair bioavailability of the product, the therapeutic efficacy, or safety
-do not interfere with required (requisite) compendial tests and assays
what are the compendial requirements for containers that are used to dispense capsules?
they must be:
-tight
-well closed
-light resistant
-and/or a combination of these
name 7 tests that are compendial requirements for capsules
disintegration test
dissolution test
weight variation
content uniformity
content labeling requirement
stability testing
moisture permeation test
explain what the disintegration test for capsules is.
what else undergoes this test?
uncoated tablets also undergo this test
capsules are placed in a basket rack and immersed 30 times/min into a 37 degree celsius thermostatically controlled fluid.
the capsules must disintegrate completely into soft mass with no firm core and only contain some fragments of the gelatin shell
explain the weight variation test.
is it form hard or soft capsules?
for both hard and soft capsules. they both have different procedures
in the content uniformity test for capsules, the capsules must be in _______ range of the labeled claim for 9/10 dosage units, with NO UNIT outside the range of ________ of the labeled claim
9/10 must be within 85%-115% of labeled claim
no unit can be outside of 75-125% of labeled claim
content uniformity is related to….
