Techniques for Compounding
Oral Nonsterile Dosage Forms:
Capsules, Tablets, Solutions,
and Suspensions
▪ Capsules are available in many different sizes and shapes
and patients can use them to administer powders,
semisolids, and liquids.
▪ The tasteless capsule can mask unpleasant ingredients to
promote palatability for oral administration and can also
CAPSULES sometimes be administered rectally or vaginally.
▪ Compounders can prepare capsules in many colors to
provide an appealing presentation, and their portability,
light weight, and rapid drug release provide additional
advantages.
▪ This solid dosage form encloses active ingredients and
excipients (inactive ingredients) in a gelatin shell or
ingetarian capsule using hydroxy propyl methyl
cellulose (HPMC capsules).
CAPSULES ▪ The shell protects the ingredients from direct exposure to
the atmosphere prior to administration and acts as a taste
barrier.
▪ The shell can be hard or soft and composed of 1 or 2 pieces.
Two-piece capsules are commonly referred to as hard-shell
capsules, while one-piece capsules are often referred to as
soft-shell capsules. Two-piece capsules consist of a base or
body, which is longer and has a smaller diameter, and a cap,
which is shorter and has a slightly larger diameter so it can
slide over the base to form a tight seal.
CAPSULES ▪ Capsules release their contents at different rates based on the
formulation and encapsulation technique. Hard gelatin
capsules can release the drug rapidly or over a predetermined
period of time, while soft gelatin capsules generally provide a
standard release rate.
▪ There are 8 sizes of gelatin capsules for human use, ranging
from the smallest, No. 5, to the largest, No. 000.
▪ Capsules of the size No. 5 through No. 0 are generally not
difficult to swallow, but patients may have difficulty swallowing
CAPSULES No. 00 and No. 000 capsules.
▪ The number assigned to a capsule is arbitrary and only offers a
relative indication of the volume. A capsule’s capacity is
dependent on the density and characteristics of the powders
used in the formulation.
▪ Sources of active ingredients include powders, tablets,
capsules, and liquids.
▪ Powders usually require no further treatment prior to their use
and are generally the easiest to work with.
▪ Tablets must be comminuted (i.e., ground into a fine powder)
to allow for incorporation into the capsule.
Compounding ▪ Compounders should only use standard release tablets for this
Steps purpose, not extended- or controlled-release tablets.
▪ Ingredients in capsules can be used by opening the capsule
shell and emptying the contents.
▪ Liquids can be evaporated to dryness or may be taken up with
an adsorbent (i.e., the adsorbent absorbs the liquid) prior to
incorporation into the capsule.
▪ Compounders should weigh and measure all ingredients. It is
recommended to measure out enough for an extra capsule or
an extra 5% to 10% to accommodate for powder loss while
compounding (except for controlled substances).
▪ If comminution is necessary, passing the ingredients through a
sieve (a fine mesh strainer or sift) may help to obtain uniform
Compounding particle sizes.
Steps ▪ Mixing the ingredients using geometric dilution (i.e., mix a
small amount of drug with an appropriate amount of a diluent)
ensures equal distribution of the drug throughout the resulting
compound. One to 2 drops of alcohol, water, or mineral oil can
help compounders to more easily manipulate difficult to
manage powders.3
▪ The capsule size selected should be slightly larger than that
needed to hold the powder and additional diluent powder
included to provide a full capsule.
Compounding ▪ Compounders should keep in mind that the larger the capsule
size the more difficult it will be for the patient to swallow.
Steps Additionally, the base of the selected capsule should hold the
entire required quantity of powder and the cap should only
serve to retain the powder.
To determine the proper capsule size, compounders can use the
following procedure:
1. Weigh the active ingredients and excipients for a single capsule
2. Mix the ingredients together, exclusive of the diluent
3. Place this quantity in a capsule base that is just slightly larger than
what is required to hold the material and replace the cap
Compounding 4. Weigh the capsule
5. Add diluent (e.g., lactose) to the capsule until it is full
Steps 6. Weigh the capsule
7. Subtract the weight obtained in step 4 from the weight obtained in
step 6; this is the required quantity of diluent for each capsule
8. Multiply by the number of capsules to be prepared to obtain the
required quantity of diluent for the total prescription
1. Preparation:
▪ Arrange the powder on a clean surface using a spatula, creating a
pile that is about one-third the length of the capsule body.
▪ It is recommended to wear gloves or fingercots to minimize
direct contact with the powder and prevent fingerprints on the
capsules.
Hand Filling 2. Filling Process:
Capsules with ▪ Press the capsule into the powder while slightly rotating it to
pack the powder tightly until slight resistance is felt.
Powder ▪ Weigh the filled capsule to ensure it meets the desired weight.
Adjust by adding or removing powder as necessary.
▪ Ensure the weight of the empty capsule is accounted for in the
measurement. Many balances can tare themselves, but if not,
use an empty capsule of the same size for accurate weighing.
Using Capsule Filling Devices
▪ If hand filling is not preferred, various manually operated capsule
Hand Filling filling devices are available.
▪ The compounder blends the ingredients as previously discussed
Capsules with and uses the device to efficiently fill the capsules, which are then
Powder ready for packaging.
1. Pipe Method:
▪ Roll the semisolid material into a pipe shape, slightly smaller in
diameter than the capsule.
▪ Cut the desired length based on the weight of the material. If
Filling Capsules needed, cornstarch or a similar substance can be added to firm
up the material.
with Semisolids 2. Melt Method:
▪ If the material is too firm to roll, it can be melted and poured into
the capsule bases. After cooling, the caps are replaced.
• Liquids can be encapsulated in hard gelatin capsules if the
gelatin is not soluble in the liquid.
• Measure the liquid accurately using a pipette or calibrated
dropper, and dispense it into the capsule base.
Filling Capsules • Before capping, soften the cap’s end by moistening it with a
with Liquids towel or warm water. Then, place the cap on the base and
twist slightly to seal.
• Optionally, a warm gelatin solution can be painted around the
inside of the cap to enhance sealing.
▪ After filling, place the finished capsules on a clean, dry surface
and inspect them for any leakage before packaging.
Final Steps
Cleaning Finished Capsules
Surface Powder Removal:
▪ Capsules should be cleaned by rolling them between folds of a
Finished Products cloth or placing them in a container with sodium bicarbonate,
sugar, or salt, and gently rolling the container.
and Quality ▪ After cleaning, pour the capsules into a 10 mesh sieve to allow
Control in Capsule the cleaning agent to pass through, ensuring that the capsules
remain clean and dry.
Compounding ▪ Note that once capsules become soiled and dull, they cannot be
effectively cleaned.
Storage, Labeling, and Packaging
• Storage Conditions:
▪ Semisolid-filled hard gelatin capsules should be stored away from
excessive heat to prevent softening or melting.
• Labeling and Packaging:
▪ The storage, labeling, and packaging of finished capsules depend
on the characteristics of the drugs they contain, ensuring proper
handling and compliance with regulations.
• Weighing Capsules:
▪ The most reliable method for ensuring accurate capsule filling is
to weigh each capsule individually. However, this is often
impractical.
▪ A more feasible approach is to weigh representative samples,
Quality Control such as weighing some capsules individually and others in groups
Measures of 10.
▪ This combined method provides data to document the accuracy
of the capsule fill, ensuring quality control throughout the
compounding process.
TABLETS
▪ Tablets are classified according to their method of
manufacturing as either molded or compressed. Molded
tablets are generally prepared by mixing the active drug with
lactose, dextrose, sucrose, mannitol, or some other
appropriate diluent that can serve as the base.
▪ One advantage of molded tablets is that they quickly
disintegrate in the presence of moisture, so the base must be
TABLETS readily absorbable in water.
▪ Once the base is added, compounders use mixtures of alcohol
and water to moisten the powder mixture so it will adhere
while being pressed into the mold cavities.
▪ The alcohol speeds up the liquid’s drying and the water causes
the sugars to dissolve and bind the tablet. Compounders can
then use a tablet titrate mold to make the tablets.
▪ The mold must be calibrated for all bases since each base is
assigned a different density depending on the nature of the
material.
TABLETS ▪ When utilizing this method, it is recommended to prepare a
slight excess of powder mixture (5% to 10%) to allow for any
variance in the mold capacity and allow for powder loss during
the compounding procedure.7
The following steps indicate how to calibrate the mold7:
1. Make and weigh tablets containing only the base and calculate
the average weight per tablet for the base
2. Make and weigh tablets containing only the active drug and
calculate the average weight per tablet for the drug
3. Divide the quantity of drug required in the prescription per
tablet by the average weight per tablet of the active drug
(quantity in step 2) to get a percentage of the cavity volume
occupied by active drug
4. Subtract the percentage in step 3 from 100% to get the
percentage of the cavity volume occupied by the base
5. Use the percentage of active drug in the cavity volume and the
percentage of base in the cavity volume to calculate the
appropriate amounts of base and drug to weigh
To create molded tablets, compounders follow these steps:
1. Preparation of Powder Mixture:
▪ The powder mixture is sifted through an 80 to 100 mesh sieve to
ensure uniformity.
2. Moistening:
▪ The powder is moistened until it reaches a consistency that allows for
easy manipulation.
3. Filling the Cavity Plate:
▪ Using a hard rubber spatula, the compounder presses the moistened
Molded Tablets mixture into the cavities of a cavity plate, ensuring all cavities are
filled evenly.
4. Pressing onto the Peg Plate:
▪ The cavity plate is then aligned and pressed onto a peg plate, which
has pegs that correspond to the holes in the cavity plate.
5. As the cavity plate falls, the tablets are pushed out onto the tops
of the pegs.
6. Drying:The tablets remain on the pegs until they dry completely.
▪ Compounded oral liquid medications play an important role in
addressing the unmet needs of special patient populations,
including pediatric, geriatric, and tube-fed patients.
▪ Solutions contain 1 or more chemical substances dissolved in
Solutions an appropriate medium.9 They can be either formulated for
direct oral administration to the patient or dispensed in a
concentrated form that requires dilution before
administration.
▪ Most solutions are prepared by simple mixing of the solute(s)
with the solvent.
▪ A solvent is defined as the liquid in which a solute is dissolved
to form a solution, and the solute is the dissolved substance.
▪ An agent’s solubility in a particular solvent indicates the
maximum concentration to which a solution may be prepared
Solutions with that combination.
▪ When a solvent has dissolved all the solute possible, it is said
to be saturated.
▪ Examples of common solvents used to prepare solutions
include ethanol, ethyl alcohol, glycerin, propylene glycol, and
purified water.9
▪ A drug’s concentration and solubility in various solvents
dictates the type of dosage form to prepare.
▪ For example, if the drug is water soluble, compounders can
prepare it as a syrup, whereas if it is soluble in water/alcohol
systems, an elixir is appropriate.
Solutions ▪ Most oral solutions contain flavoring and coloring agents,
stabilizers (if needed) to maintain physical and chemical
stability, and preservatives to prevent microbial growth.
▪ In some cases, a buffering agent may be necessary if the pH of
the vehicle influences the drug’s solubility.9
▪ Compounders must be aware of all ingredients’ physical and
chemical properties to ensure there are no incompatibilities.
When solubilizing drugs, compounders should consider the
following:
• Small particles dissolve faster than large particles
• Stirring increases the dissolution rate
• The more soluble the drug, the faster the dissolution rate
• A viscous (i.e., thick) liquid will decrease the dissolution rate
• A temperature increase generally leads to increased solubility
and dissolution rates
• The solubility of poorly soluble acidic substances increases as
the medium’s pH increases
• The solubility of poorly soluble basic substances increases as
the medium’s pH decreases
▪ Compounders usually prepare syrups using one of 4 general methods
depending on the ingredient’s physical and chemical characteristics9:
1. Heat: The compounder adds sugar to purified water and applies heat until
the sugar dissolves. They add other components to the hot syrup, allow the
mixture to cool, and adjust the final volume to the proper level by adding
purified water.
2. Agitation: The compounder dissolves sugar and other agents in purified
water by placing the ingredients in a vessel and stirring to dissolve the
substances. This process is more time consuming than using heat.
Compounding 3. Percolation: The compounder percolates the sugar (i.e., passes it through a
Syrups filter) to prepare the syrup or percolates the active ingredient and then
adds the sucrose or syrup.
4. Adding sucrose to a medicated/flavored liquid: Occasionally an active
ingredient will already be supplied in liquid form. If the active ingredient is
water soluble, compounders can add it to the sucrose. If the active
ingredient is only soluble in alcohol and not water, compounders must use
some means of rendering it water before adding sucrose to prepare the
syrup.
▪ Compounders usually prepare elixirs by agitation and/or by
mixing 2 or more liquid ingredients.
▪ Generally, they dissolve alcohol- and water-soluble
components separately in alcohol and purified water,
respectively.
Compounding ▪ They then add the water solution to the alcoholic solution so
Elixirs that minimal separation of the alcohol-soluble components
occurs.
▪ When the 2 solutions are completely mixed, the compounder
uses the specified solvent or vehicle to adjust to the desired
volume.
▪ Individuals use spirits as flavoring agents or for the therapeutic
value of their aroma.
▪ The alcoholic concentration of spirits is rather high, usually
over 60%, and so people generally mix them with water to
reduce their pungency.
▪ Compounders can prepare spirits by making a simple solution
Compounding with a compatible solvent, solution by maceration (i.e.,
Spirits extracting the drug by allowing it to stand in a solvent), or by
distillation (i.e., separating the components of a liquid based
on different boiling points).
▪ Some examples of spirits listed in the USP are aromatic
ammonia spirit, camphor spirit, compound orange spirit, and
peppermint spirit.9
▪ People should store most finished oral liquid products at room
temperature or refrigerated, depending on product
characteristics.
Finished ▪ Syrups are often refrigerated to enhance their stability and
palatability. In some cases, precipitation (i.e., when a solid
Products and settles out of a solution) can occur with a refrigerated product,
Quality Control and in most cases, the precipitate (i.e., the solid portion) will
redissolve when the solution is returned to room temperature.
If not, individuals can gently warm the preparation to
redissolve the precipitate.
▪ Quality control procedures include checking the final volume,
appearance, odor, clarity, osmolality, refractive index, specific
gravity, and pH of the final solution.
▪ Pharmacies can purchase inexpensive pH meters to verify the
Finished final pH of a preparation, but they may outsource more
Products and complicated quality assurance tests.
Quality Control ▪ Solutions are particularly susceptible to chemical degradation,
especially when aqueous vehicles are used. Compounders
should visually examine them to check for evidence of
precipitation, mold or bacterial growth, odor, and volume loss.
▪ Suspensions are appropriate when the drug to be incorporated
is not sufficiently soluble in a solvent.
▪ A properly compounded suspension ensures that the drug is
uniformly dispersed throughout the vehicle to ensure that
each time the patient measures the appropriate dose they
receive the same amount of active ingredient.
Suspensions ▪ A suitable vehicle for suspensions has the necessary viscosity
to keep drug particles suspended separately from each other
but is sufficiently fluid to allow the preparation to be poured
from the container.
▪ Suspensions have many advantages, including increased
palatability and stability when drugs are insoluble, and they
offer the administration of insoluble powders.
▪ In addition to being efficacious, chemically stable, and
aesthetically appealing, a compounded suspension should also
include the following features12:
• The suspension should settle slowly, otherwise accurate
measurement of a dosage is difficult and an unsightly
supernatant layer becomes visible (i.e., a liquid layer above the
solid layer)
• The particle size of the suspended ingredient should remain
fairly constant throughout long periods of undisturbed
standing
• The suspension should pour readily and evenly
▪ When compounding a suspension, an individual empties the
contents of a capsule into a mortar or crushes tablets in a
mortar with a pestle.
▪ Then, they should thoroughly wet the active, insoluble
material before mixing it with the vehicle. Some examples of
Compounding wetting agents include glycerin, benzalkonium chloride, and
polysorbate 20, 40, 60 or 80.
Steps ▪ Wetting agents reduce the surface tension of the water and
increase the spreadability of the liquid.
▪ The compounder then slowly adds the selected vehicle, mixes
to create a paste, then dilutes that paste to the desired
volume.
▪ Sometimes, compounders add suspending agents (also known
as thickening agents) to lend structure to the dispersion
medium, and they often use preservatives to prevent microbial
Finished growth.
▪ Some examples of suspending agents include
Products and carboxymethylcellulose, methylcellulose, microcrystalline
Quality Control cellulose, and xanthan gum.
▪ Individuals can also flavor and sweeten suspensions to meet
the patient’s preferences.
▪ Finished products should be packaged in light-resistant
containers leaving adequate air space to permit thorough
mixing by shaking.
▪ Compounders should label suspensions with a “shake well”
auxiliary label and instruct patients or caregivers to refrigerate
the product and to watch for any color or consistency change
indicating a stability problem.12
▪ Quality control for finished suspensions involves checking the
volume, extent of settling, ease of dispersibility, appearance,
odor, and pourability.13 The amount of settling can be
measured by allowing the product to sit for a day and then
measuring the height of the settled particles.13 Individuals
should periodically check the product for these characteristics
if it has remained on the pharmacy shelf for an extended
period of time.