Capsules Flashcards
Capsule
a solid dosage form in which medicinal agents and/or inert substances are enclosed in a small shell of gelatin
Gelatin
protein obtained by partial hydrolysis of collagen derived form bovine or porcine skin and bone
- Derived from skin, has plasticity
- Derived from bone, has firmness
Bloom strength should be approximately 150-280g
- Stable in air when dry, but is subject to microbial decomposition when it becomes moist
Non-animal derived alternatives of gelatin
Hydroxypropyl methylcellulose, starch and carrgeenan capsules
Advantages of capsules
- Can be used to deliver powders, granules, beads and prefabricated tablets, semisolids and liquids that do not dissolve gelatin
- Can mask taste and odor of drug
- Are easy to swallow
- Generating, rate of drug absorption after oral administration : Capsule > tablet
- Can be administered orally, rectally and vaginally
Disadvantages of capsules
- Sensitive to relative humidity
- Not suitable for liquids that dissolve gelatin
- Some can be tampered with
Plasticizers
Reduce rigidity of gelatin, making it more pliable
Ex: Water, Sorbital and propylene glycol
Preservatives
Reduce bacterial and fungal growth
Ex: Methylparaben and propylparaben
Colorants
Change color
Ex: Azo and xanthene dyes and iron oxide pigments
Opacifiers
Makes clear gelatin opaque, which can protect contents from light
Ex: Titanium dioxide
Hard gelatin capsules
Made of gelatin, sugar and water, and may contain colorants, opaquants
and preservatives
Shells normally have moisture content of 13-16%
– If too dry it becomes brittle
– If too moist it becomes soft and sticky
Hard gelatin capsules are made how
Manufactured in two parts:
- Capsule body
- Shorter cap
Produced by mechanical dipping and then spinning of pins or pegs into a
temperature-controlled (50 C) reservoir of melted gelatin mixture
The two parts overlap when joined, with the cap fitting snugly over the open end of
the capsule body
Hard gelatin capsule sizes
Various sizes: 000 (largest) to 5 (smallest) for human use
- Largest size capsules carry more weight of drug
Capsule sizes
- Capsules can be used to encapsulate between 65 and 1000 mg of powdered material
- Some patients have difficulty swallowing larger capsules
-Some patients find smaller capsules hard to handle - If the active drug powder is large, the total amount can be divided into two smaller
capsules that are easier to swallow - If the active drug powder is small, more diluent can be added to increase the size of a
capsule for handling convenience
Rule of sizes
When the bulk density of powders is between 0.4 and 0.8 g/mL w an average of 0.6 g/mL, the size of the capsule can be approximated by the rule of sixes
- Each grain is equivalent to 0.065 g or 65 mg
Number 6 - Capsule size = weight of powder in grains
For example 6 - Capsule size 1 is 5. So 5 grains = 325 mg of powdered drug can be filled in capsule size #1
Rule of sevens
- Convert weight of powder per capsule to grains (1 grain = 0.065 g);
- subtract the number of grains from 7; and
- match the result to the following list
Resulting number Capsule Size
-3 000
-2 00
-1 or 0 0
1 1
2 2
Method does not work if the resulting number is higher than 5 or lower than -3
Preparation of hard gelatin capsules
- developing and preparing the formulation and selecting capsule size
- filling the capsule shells
- capsule sealing (optional)
- cleaning and polishing the filled capsules
Formulation for hard capsules
prepare a capsule with accurate dosage, good bioavailability, ease of filling
and production, stability and elegance
Suitable for dry formulations; active and inactive components must be blended
thoroughly to ensure a uniform powder mix for the fill
Inactive components (or excipients) important in the manufacture of hard capsules
- Diluent (or filler)- for adding bulk and cohesion to the powders
Ex: Lactose, microcrystalline
cellulose and starch - Disintegrants- to assist breakup and distribution of capsule contents in the stomach
Ex: Pregelatinized starch, croscarmellose and sodium starch glycolate - Lubricant, to enhance flow properties of powder or granule for ease of filling
Ex: Fumed silicon
dioxide, magnesium stearate and talc - Surfactant- to improve water penetration into the powder
Ex: Sodium lauryl sulfate and
polysorbate 80
Formulation for hard capsule pt 2
Some liquids, such as oils, that do not interfere with the stability of the
capsule, may be placed in locking or sealed hard capsules
Liquid may be mixed with an inert powder to make a wet paste, and then
inserted
Eutectic mixtures may be mixed with diluent or absorbent such as magnesium
carbonate, kaolin or light magnesium oxide which will separate the interacting
agents in order to absorb the liquefied material that forms
NOT suitable for aqueous liquids
- soft gelatins and distorts, resulting in leakage of contents
Extemporaneous filling of capsules
Filled capsules should be neither underfilled nor overfilled, but should hold the ingredients snugly
Capsule size should be selected that accommodates the fill and will be easily swallowed
The steps used in calculating the proper capsule fill
- Select appropriate capsule size
- Fill the capsule shell separately with each drug and diluent, and record weights of each
- Calculate diluent displacement weight for each drug
- Calculate the amount of diluent required per capsule
- Calculate the total quantities of each drug and the diluent needed to fill all of the capsules
prescribed
Punch method
when calculating the amount of drug substance and
diluent required, usually an extra dose (an additional 5-10% of the formulation) is
added to account for ingredient loss during filling
In Pharmaceutics and Skills Lab, we will account for 2 extra capsules or 10% excess,
whichever is greater
Geometric dilution
ensures that drugs are distributed uniformly throughout the mix
Filling hard gelatin capsules via “punch method”
- Nitrile gloves should be worn to avoid fingerprints on the capsules
- The powder mixture is placed on the sheet of clean paper, glass or porcelain pill tile
- With a spatula, the powder is shaped into a cake having a depth of approximately 1/4
to 1/3 the length of the capsule; - Remove the capsule cap from the capsule body
- The empty capsule body is held between the thumb and forefinger and is punched
vertically into the powder cake with a slight twist motion; repeat until the capsule is
filled to ensure equal and accurate filling - Replace the capsule cap and tap the capsule on the cap end to distribute the
contents evenly - You should try to note signs such as “crunching” of the powder as the capsule fills
and the pressure needed to fill each capsule; these will be useful indicators, which
can help you in filling the capsule consistently - The capsules should be weighed to assure consistency of weight
- The final step of filling a capsule is to polish the capsules with a paper towel to
remove any powder from the outside of the capsule
Capsule filling machine
Large quantities of various capsules can be compounded in a very short amount of
time
the compounder should NOT calculate and use
excess powder; loss of powder is minimal, and since all powder must be packed into
the capsules, the risk of overdosing is great
Soft gelatin capsules
Soft capsules contain appreciable
quantities of a plasticizer other than water which makes the gelatin is more flexible
- Must be compatible with gelatin
- Can be oblong, oval or round
-Typically formed, filled and sealed in one continuous operation
Liquids that may be encapsulated
into soft capsules
- Water-immiscible volatile and nonvolatile liquids
- Water-miscible nonvolatile liquids
- Water-miscible and relatively nonvolatile compounds
Liquids that can easily migrate through the capsule shell are NOT suitable; these
materials include water above 5% and low-molecular-weight water-soluble and
volatile organic compounds
Preparation of soft gelatin capsules
Plate process and rotary die process
Plate process
- Warm sheet of gelatin placed on bottom plate of mold.
- Medication-containing liquid evenly poured on it
- A second sheet of gelatin placed on top of the medication
- Top plate of the mold
put on top - Pressure is applied to the mold to form, fill and seal the capsules simultaneously,
the capsule removed and washed with a solvent harmless to the capsules
Rotary die process
- Most commonly prepared using this method
- Liquid gelatin flowing from an overhead tank is formed into two continuous ribbons by the rotary die machine and brought together between twin rotating dies, metered fill material is injected between the ribbons precisely at the moment that the dies form pockets of the gelatin ribbon, these pockets of fill-containing gelatin are sealed by pressure and heat and then severed from the ribbon
- The reciprocating die process is similar in that ribbons of gelatin are formed to encapsulate the fill, but it differs in the encapsulating process
Substances added to enhance stability, usefulness, elegance, or to facilitate
their manufacture, may be used ONLY if they:
- Are harmless in the quantities used
- Do not exceed the minimum amounts required to provide their intended effect
- Do not impair the product’s bioavailability, therapeutic efficacy or safety
- Do not interfere with requisite compendial assays and tests
Disintegration test for hard and soft capsules
they are placed in
basket assembly, which is immersed 30 times per minute into fluid at 37 °C,
and observed over time until capsules disintegrate completely into a soft
mass with no firm core and only some fragments of the gelatin shell
Dissolution test for capsules
Using special apparatus and dissolution medium to predict how the solid will
enter solution in vivo; in cases where shell interferes, contents of a specified
number of capsules can be removed and the empty shell dissolved before
proceeding with the sampling and chemical analysis
Weight variation for hard capsules
To determine content of the active ingredient
– Hard capsules – 10 capsules are individually weighed and their contents removed, the emptied shells are individually weighed and the net weight of the contents are calculated by subtraction
Weight variation for soft capsules
– Soft capsules – The gross weight of 10 intact capsules is determined individually
- Then each capsule is cut open and the contents are removed by washing with a
suitable solvent, the solvent allowed to evaporate, individual shells are weighed
and net contents calculated
Content uniformity
The quantity of each active ingredient must be within the range of 85-115% of the
label claim for 9 of 10 dosage units assayed, with no unit outside the range of 70-
125% of the label claim
Content labeling
All capsules must be labeled to express quantity of each active ingredient
Stability testing
Intrinsic stability of the active drug molecule and the influence of environmental
factors like temperature, humidity, and light are determined
The battery of stress testing, long-term stability and accelerated stability tests help determine appropriate conditions for storage and the product’s anticipated shelf-life
Moisture permeation test
Degree and rate of moisture penetration are determined by packaging the dosage unit together with a color-revealing desiccant pellet
Exposing the packaged unit to known relative humidity over a specified time
Then we observe the
desiccant pellet for color change (indicating the absorption of moisture) and
comparing the pretest and posttest weight of the packaged unit
This assures
suitability of packaging
Inspecting, counting, packaging and storing capsules
Should be uniform in appearance; visual or electronic inspection should be undertaken to detect any flaws
May be counted manually using a specially designed tray, such as the Abbott
Sanitary Counting Tray, or by automated equipment
Packaged in glass or in plastic containers, some containing packets of a desiccant to
prevent absorption of excessive moisture, and should be stored in tightly capped
containers in a cool, dry place
