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GIPER
A Brief overview on Capsule
For Bachelor Student
Akash Mali
18/05/2015
A Brief overview on Capsule
1.Introduction :-
Capsule is the most versatile of all dosage forms. Capsules are solid dosage forms in
which one or more medicinal and inert ingredients are enclosed in a small shell or container
usually made of gelatin.
There are two types of capsules, “hard” and “soft”. The hard capsule is also called “two
piece” as it consists of two pieces in the form of small cylinders closed at one end, the shorter
piece is called the “cap” which fits over the open end of the longer piece, called the “body”.
The soft gelatin capsule is also called as “one piece”. Capsules are available in many sizes to
provide dosing flexibility. Unpleasant drug tastes and odors can be masked by the tasteless
gelatin shell. The administration of liquid and solid drugs enclosed in hard gelatin capsules is
one of the most frequently utilized dosage forms.
Advantages of Capsules :-
• Capsules mask the taste and odor of unpleasant drugs and can be easily administered.
• They are attractive in appearance
• They are slippery when moist and, hence, easy to swallow with a draught of water.
• As compared to tablets less adjuncts are required.
• The shells are physiologically inert and easily and quickly digested in the gastrointestinal
tract.
• They are economical
• They are easy to handle and carry.
• The shells can be opacified (with titanium dioxide) or colored, to give protection from light.
Disadvantages of Capsules:-
• The drugs which are hygroscopic absorb water from the capsule shell making it brittle and
hence are not suitable for filling into capsules.
• The concentrated solutions which require previous dilution are unsuitable for capsules
because if administered as such lead to irritation of stomach.
2.Raw Materials for Capsules :-
The raw materials used in the manufacture of both hard and soft gelatin capsules are
similar. Both contain gelatin, water, colorants and optional materials such as process aids and
preservatives.
A) Gelatin – gelatin is the major component of the capsules and has been the material
from which they have traditionally been made. Gelatin has been the raw material of
choice because of the ability of a solution to gel to form a solid at a temperature just
above ambient temperate conditions, which enables a homogeneous film to be formed
rapidly on a mould pin.
The reason for this is that gelatin possesses the following basic properties:
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• It is non-toxic, widely used in foodstuffs and acceptable for use worldwide.
• It is readily soluble in biological fluids at body temperature.
• It is good film-forming material, producing a strong flexible film
• The gelatin films are homogeneous in structure, which gives them strength.
Some of the disadvantages with using gelatin for hard capsules include: it has a high moisture
content, which is essential because this is the plasticizer for the film and, under International
Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals
for Human Use (ICH) conditions for accelerated storage testing, gelatin undergoes a cross
linking reaction that reduces its solubility.
Gelatin is a translucent brittle solid substance, colorless or slightly yellow, nearly tasteless and
odorless, which is created by prolonged boiling of animal skin connective tissue or bones.
Type A gelatin is derived from an acid-treated precursor and exhibits an isoelectric point in the
region of pH 9, whereas type B gelatin is from an alkali-treated precursor and has its
isoelectric zone in the region of pH 4.7. Capsules may be made from either type of gelatin,
but mostly a mixture of both types is used considering availability and cost. Difference in the
physical properties of finished capsules as a function of the type of gelatin used is slight.
Blends of bone and pork skin gelatins of relatively high strength are normally used for hard
capsule production. The bone gelatin produces a tough, firm film, but tends to be hazy and
brittle. The pork skin gelatin contributes plasticity and clarity to the blend, thereby reducing
haze or cloudiness in the finished capsule.
Physical properties of gelatin:
Gelatin is a protein product produced by partial hydrolysis of collagen extracted from skin,
bones, cartilage, ligaments, etc. The natural molecular bonds between individual collagen
strands are broken down into a form that rearranges more easily. Gelatin melts when heated
and solidifies when cooled again. Together with water it forms a semi-solid colloidal gel.
Production of gelatin:
On a commercial scale, gelatin is made from by-products of the meat and leather industry,
mainly pork skins, pork and cattle bones, or split cattle hides. Contrary to popular belief,
horns and hooves are not commonly used. The raw materials are prepared by different curing,
acid, and alkali processes which are employed to extract the dried collagen hydrolysate. The
entire process takes several weeks. The flow chart for gelatin production has been shown in
figure 1.
B) Colorants – The color of pharmaceutical product plays an important role in their use.
Color is used principally to identify a product in all stages of its manufacture and use. In the
manufacturing company it assists in complying with GMP norms by helping the operators
differentiate between products. The colorants that can be used in capsules are of two types:
water soluble dyes or insoluble pigments. To make a range of colors dyes and pigments are
mixed together as solutions or suspensions. Three most commonly used dyes are erythrosine,
indigo carmine and quinolone yellow. The two types of pigments used are iron oxides- black,
red and yellow and titanium dioxide which are white and used to make the capsule opaque.
Capsules are colored by the addition of colorants to the gelatin solution during the
A Brief overview on Capsule
manufacturing stage.
Gelatin Production Processes
Degreased dried crushed bone Pig skins
Acid Treatment Chopping
Lime treatment Water wash
Washing Acid treatment
Acid treatment Washing
Multiple hot water extraction
Filtration
Ion exchange deionization
Evaporation
Filtration
Final concentration
Sterilization
Polish filtration
Chilling to set point
Extrusion
Drying
Milling
Blending and Packing
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Figure 1: Flow chart for gelatin production process
B) Process aids – Preservatives and surfactants are added to the gelatin solution during
capsule manufacture to aid in processing. Gelatin solutions are an ideal medium for
bacterial growth at temperatures below 55 C. preservatives are added to the gelatin and
colorant solutions to reduce the growth of microorganisms until the moisture content
of the gelatin film is below 16% w/v. at moisture content below that value, the
bacterial population will decline in numbers with time. The materials used as
preservatives include: sulfur dioxide which is added as the sodium salts bisulfite or
metabisulfite, sorbic acid or the methyl propyl esters of para- hydroxy-benzoic acid,
and the organic acids, benzoic and propanoic acids.
Some hard gelatin capsules may contain 0.15 % w/w of sodium lauryl sulphate which
functions as wetting agent, to ensure that the lubricated metal moulds are uniformly covered
when dipped into the gelatin solution. Capsules are available in many different sizes and
shapes and can be used for the administration of powders, semisolids and liquids. Unpleasant
tastes and odors of drugs are effectively masked by the practically tasteless capsule shell
which dissolves or is digested in the stomach after about ten to twenty minutes. Capsules also
can be used as a means of providing accurately measured doses for administration rectally or
vaginally.
3. Manufacture of hard gelatin capsules :-
Steps involved in making hard gelatin capsules…
a) Dipping
b) Spinning
c) Drying
d) Stripping
e) Trimming and Joining
f) Polishing
a) Dipping -
Pairs of the stainless steel pins are dipped into the dipping solution to
simultaneously form the caps and bodies. The dipping solution is maintained at a
temperature of about 500C in a heated, jacketed dipping pan.
b) Spinning –
The pins are rotated to distribute the gelatin over the pins uniformly and to avoid
the formation of a bead at the capsule ends.
c) Drying –
The gelatin is dried by a blast of cool air to form a hard shells.
The pins are moved through a series of air drying kilns to remove water.
d) Stripping –
A series of bronze jaws strip the cap and body portions of the capsules from the
pins.
e) Trimming and joining –
The stripped cap and body portions are trimmed to the required length by
stationary knives.
A Brief overview on Capsule
After trimming to the right length, the cap and body portion are joined and
ejected from the machine.
f) Polishing –
Pan Polishing : Acela-cota pan is used to dust and polish.
Cloth Dusting :Capsule are rubbed with cloth.
Brushing : Capsule are feed under soft rotating brush.
Types of materials for filling into hard gelatin capsules:
Dry solids – powders, pellets, granules or tablets
Semisolids – suspensions or pastes
Liquids – non - aqueous liquids
A capsule size chart is shown in table 1.
4) Capsule shell filling :-
Hand operated hard gelatin capsule filling machines – hand operated and electrically
operated machines are in practice for filling the capsules but for small and quick dispensing
hand operated machines are quite economical.
A hand operated gelatin capsule filling machine consists of the following parts and is shown
in figure 2.
1. A bed with 200-300 holes.
2. A capsule loading tray
3. A powder tray
4. A pin plate having 200 or 300 pins corresponding to the number of holes in the bed
and capsule loading tray.
5. A lever
6. A handle
7. A plate fitted with rubber top.
Table 1: Size of hard gelatin capsules -Capsule size chart
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Empty Hard Gelatin Capsule Physical Specifications
Size
Outer
Diameter(mm)
Height or Locked
Length (mm)
Actual Volume
(mL)
Typical Fill
Weights(mg)
0.70 Powder
Density
000 9.91 26.14 1.37
960
00 8.53
23.30
0.95 665
0 7.65
21.70
0.68 475
1 6.91 19.40 0.50 350
2
6.35 18.00 0.37 260
3
5.82 15.90 0.30 210
4 5.31 14.30 0.21
145
5 4.91 11.10
0.13 90
(Source-Remington –The Science and Practice of Pharmacy,20 th Edition,Volume–1)
All parts of the machine are made up of stainless steel. The machines are generally supplied
with additional loading trays, beds, and pin plates with various diameters of holes so as to fill
the desired size of the capsules. These machines are very simple to operate, can be easily
dismantled and reassembled
A Brief overview on Capsule
Figure 2: Hand operated hard gelatin capsule filling machine
(Source: Remington – The Science and Practice of Pharmacy, 20 th Edition, Volume 1,
courtesy – Park Davis)
Working: The empty capsules are filled into the loading tray which is then placed over the
bed. By opening the handle, the bodies of the capsules are locked and caps separated in the
loading tray itself which is then removed by operating the liver. The weighed amount of the
drug to be filled in the capsules is placed in powder tray already kept in position over the bed.
Spread the powder with the help of a powder spreader so as to fill the bodies of the capsules
uniformly. Collect excess of the powder on the platform of the powder tray. Lower the pin
plate and move it downward so as to press the powder in the bodies. Remove the powder tray
and place the caps holding tray in position. Press the caps with the help of plate with rubber
top and operate the lever to unlock the cap and body of the capsules. Remove the loading tray
and collect the filled capsules in a tray. With 200 hole machine about 5000 capsules can be
filled per hour and with300 hole machine 7500 capsules can be filled per hour.
On large-scale manufacturing various types of semiautomatic and automatic machines are
used.
They operate on the same principle as manual filling, namely the caps are removed, powder
filled in the bodies, caps replaced and filled capsules are ejected out. With automatic capsule
filling machines powders or granulated products can be filled into hard gelatin capsules. With
accessory equipment, pellets or tablets along with powders can be filled into the capsules.
5) Capsule filling devices :-
A number of different manually operated capsule filling devices are commercially
available for filling up to 50 or 100 capsules at a time. The method of using these machines
requires a careful determination of the capsule formulation. The powder is blended as
previously discussed. Empty gelatin capsules are placed into the device and, oriented so that
the cap is on top. The machine is worked to separate the base from the cap and the portion of
the machine holding the caps is removed and set aside.
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The capsule bases are allowed to “drop” into place so that the tops are flush with the
working surface. The powder mix is spread over the working surface. A plastic spatula can be
used carefully to spread the powder uniformly and evenly into the capsule bases or the
machine can be“tapped” to spread the powder and drop it down into the capsule bases. A
small device consisting of several “pegs” on a handle can be used to tamp the powder into the
capsule bases gently and evenly. Any remaining powder then is spread evenly over and into
the capsule bases and tamped. These procedures are repeated until all of the powder is in the
capsules. The capsule caps are then fitted over the machine, fixed in place, and the filled
capsules removed, dusted using a clean cloth, and packaged.
A process flow diagram for automated capsule filling is shown in figure 3.
Figure 3: Process flow diagram for automated capsule filling
(Source – Textbook of Pharmaceutics by Bentley, 8 th Edition)
A Brief overview on Capsule
Filling capsules with a semisolid mass:
If the material to be placed into hard gelatin capsules is a semisolid, it can be
encapsulated by either forming a pipe or pouring a melt.
1.Pipe: If the material is sufficiently plastic, it can be rolled into a pipe with a diameter
slightly less than that of the inner diameter of the capsule in which it will be enclosed. The
desired quantity of material is cut using a spatula or knife, the length determining the weight
of the material enclosed. The pieces may be dusted with corn starch (check patient allergies)
prior to individual insertion into the capsules.
If a material is too fluid to be worked as described, it may be necessary to add
cornstarch or some similar material to yield a more firm consistency. The quantity to be added
can be determined empirically.
2. Semisolid pour: If the material is too firm to roll into a pipe but its melting point is
satisfactory, it can be melted and poured into the capsule bases, cooled, and the caps replaced.
A stand to hold the capsule bodies may be fashioned from a block of wood into which a series
of holes the diameter of the capsule caps is drilled. When capsule caps are glued into these
holes, capsule bases may be inserted for filling without scratching or marking by the wood.
This method also can be used to enhance the bioavailability of drugs, which are poorly
soluble and exhibit bioavailability problems. For this purpose, the drug is added to a melt of a
material such as polyethylene glycol (PEG). The mixture is heated and stirred until the
powder is either melted or thoroughly mixed in the PEG. The melt is cooled to just above the
melting point of the PEG and poured into the capsule shells as described. When this method is
used, the desired quantities can be measured using a pipet, syringe, or calibrated dropper to
deliver the volume to the individual capsules.
Liquids in Hard Gelatin Capsules –
Liquids can be prepared in hard gelatin capsules if the gelatin is not soluble in the liquid
to be encapsulated; alcoholic solutions and fixed and volatile oils work well. It may be
necessary to determine the solubility of gelatin in the liquid by experimentation. The liquid
can be measured accurately using a pipette (micropipet) or a calibrated dropper and dropped
into the gelatin base, taking care not to touch the opening. The gelatin caps can be touched,
open end down, on a moist towel to soften the gelatin at the opening of the caps or a cotton
swab dipped in warm water can rubbed around the edge of the capsule cap to soften. The cap
is placed over the base containing the liquid with a slight twist and the softened edge of the
cap should form a seal with the base to prevent leakage. Prior to packaging, these capsules
should be placed on a clean, dry sheet of paper and observed for leakage. Another method of
sealing makes use of a warm gelatin solution that is painted around the capsules and the inside
of the caps prior to placing on the base.
Industrial scale filling –
The machines for industrial -scale filling of hard gelatin capsules come in great variety
of shapes and sizes, varying from semi- to fully automatic and ranging in output from 5000 to
15000 per hour. Automatic machines can be either continuous in motion, like a rotary tablet
press, or intermittent, where the machine stops to perform a function and then indexes round
to the next position to repeat the operation on a further set of capsules. The capsule filling
process is illustrated in figure 4.
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Figure 4: The capsule filling process
The dosing systems can be divided into two groups:
Dependent – dosing systems that use the capsule body directly to measure the powder.
Uniformity of fill weight can only be achieved if the capsule is filled completely eg. Auger
filling.
Independent – dosing systems where the powder is measured independently of the body in a
special measuring device. Weight uniformity is not dependent on filling the body completely.
With this system the capsules can be part filled eg. Dosator. An illustration of dosator
principle is shown in figure 5.
Figure 5: Dosator principle of filling capsule
(Source - Modern Pharmaceutics by Gilbert S. Bankers, 4 th Edition, Dekker series)
A Brief overview on Capsule
Types of excipients used in powder-filled capsules
Diluents – diluents are the excipients that are usually present in the greatest concentration in a
formulation and they make up the necessary bulk when the quantity of the active ingredient is
insufficient to make up the required bulk eg. Lactose, maize starch, calcium sulfate etc.
Lubricants and Glidants – which reduce powder to metal adhesion and promote flow
properties eg. Magnesium stearate, talc.
Wetting agents – which improve water penetration for poorly soluble drugs eg. Sodium
lauryl sulfate
Disintegrants – which produce disruption of the powder mass crospovidone, sodium starch
glycolate.
6) Cleaning and Packaging :-
It is imperative that every precaution to minimize traces of moisture or body oils on
capsules be taken to reduce powders sticking to the surface, which would create disagreeable
appearance and taste. Cleaning capsules is difficult if they have become moist or sticky. The
capsules should be handled so that they retain their dryness and shiny appearance. Use of
gloves provides a more hygienic environment and helps preserve the dry, shiny capsule
appearance. An old method, where gloves are unavailable, is: (1) Wash and dry hands
thoroughly,
(2) Keep the fingers dry by the friction of a towel that is stripped through the tightly clenched
fingers until a clearly perceptible heat is generated,
(3) Four or five capsules may be prepared before there will be a need to repeat the process. If
the capsules have been kept dry, clinging surface powder can be removed by rolling between
folds of a cloth or by shaking in a cloth formed into a bag or hammock. Another method of
cleaning capsules is to place them in a container that is filled with sodium bicarbonate, sugar
or salt then gently to roll the container. The contents then can be poured into a 10 mesh sieve
and the“ cleaning salt” allowed to pass through the screen, which collects the capsules. It must
be emphasized that these cleaning methods are only effective if the capsules have been kept
clean and dry. Once capsules become soiled and dull, they cannot be cleaned effectively.
ROTOSORT is a new filled capsule-sorting machine sold by Eli Lilly and Company. It is a
mechanical sorting device that removes loose powder, unfilled joined capsules, filled or
unfilled bodies, and loose caps. It can handle up to 150,000 capsules per hour, and it can run
directly off a filling machine or be used separately.
Difficulties in filling capsules
1.Deliquescent or Hygroscopic powders – a gelatin capsule contain water which is
extracted or taken up by a hygroscopic drug and renders the capsule very brittle which leads to
cracking of the capsule. The addition of an adsorbent like magnesium carbonate, heavy
magnesium oxide or light magnesium oxide overcomes this difficulty provided the capsules
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are packed in tightly closed glass capsule vials.
2.Eutectic mixtures – certain substances when mixed together tend to liquefy and form
a pasty mass due to the formation of a mixture which has a lower melting point than room
temperature. For filling these types of substances each troublesome ingredient is mixed with
an absorbent separately then mixed together and filled in capsules. The absorbents used are
magnesium oxide and kaolin. Another method in dealing with such type of difficulty is that
the substances are mixed together so as to form a eutectic mixture, then an absorbent like
magnesium carbonate or kaolin is added.
3.Addition of inert powders – when the quantity of the drug to be filled in capsules is
very small and it is not possible to fill this much small amount in capsules then inert substance
or a diluent is added so as to increase the bulk of the powder, which can be filled easily in
capsules.
4. Use of two capsules – some of the manufacturers separate the incompatible ingredients
of the formulation by placing one of the ingredients in smaller capsule, and then placing this
smaller capsule in a larger capsule containing the other ingredients of the formulation.
5. Filling of granular powder – some powders which lack adhesiveness and most granular
powders are difficult to fill in the capsules by punch method because they are not
compressible and flow out of the capsule as soon as they are lifted from the pile of powder
into which they are punched. To overcome this difficulty the non-adhesive
powders should be moistened with alcohol and the granular powders should be reduced to
powder before filling into capsules.
Alternative material for Hard-shell capsules - Several materials have been examined as a
substitute for the gelatin in two-piece hard capsules. Hydroxypropylmethyl cellulose (HPMC)
has become a successful alternative material for two- piece capsules and is actually on the
market in the world. HPMC capsules have been developed for both pharmaceutical products
and dietary supplements. QUALI-V, developed by Shionogi Qualicaps, is the first HPMC
capsule developed for eventual use in Pharmaceutical products.
7) Quality control of capsules :-
Whether capsules are produced on a small scale or large scale all of them are required to
pass not only the disintegration test, weight variation test and percentage of medicament test
but a visual inspection must be made as they roll off the capsule machine onto a conveyor belt
regarding uniformity in shape, size, color and filling. As the capsules moves in front of the
inspectors the visibly defective or suspected of being less than the perfect are picked out.
The hard and soft gelatin capsules should be subjected to following tests for their
standardization.
1. Shape and size
2. Color
3. Thickness of capsule shell
4. Leaking test for semi-solid and liquid ingredients from soft capsules
5. Disintegration tests
A Brief overview on Capsule
6. Weight variation test
7. Percentage of medicament test
In official books the following quality control tests are recommended for capsules:
Disintegration test: For performing disintegration test on capsules the tablet disintegration
test apparatus is used but the guiding disc may not be used except that the capsules float on
top of the water. One capsule is placed in each tube which are then suspended in the beakers
to move up and down for 30 minutes, unless otherwise stated in the monograph. The capsules
pass the test if no residue of drug or other than fragments of shell remains on No. 10 mesh
screen of the tubes.
Weight variation test: 20 capsules are taken at random and weighed. Their average weight is
calculated, then each capsule is weighed individually and their weight noted. The capsule
passes the test if the weight of individual capsule falls with in 90-110% of the average weight.
If this requirement is not met, then the weight of the contents for each individual capsule is
determined and compared with the average weight of the contents. The contents from the
shells can be removed just by emptying or with the help of small brush. From soft gelatin
capsules the contents are removed by squeezing the shells which has been carefully cut. The
remainder contents are removed by washing with a suitable solvent. After drying the shells,
they are weighed and the content weights of the individual capsules are calculated. The
requirements are met if (1) not more than 2 of the differences are greater than 10 % of the
average net content and(2) in no case the difference is greater than 25 %.
Content uniformity test: This test is applicable to all capsules which are meant for oral
administration. For this test a sample of the contents is assayed as described in individual
monographs and the values calculated which must comply with the prescribed standards.
Capsule stability: Unprotected soft capsules (i.e., capsules that can breathe) rapidly reach
equilibrium with the atmospheric conditions under which they are stored. This inherent
characteristic warrants a brief discussion of the effects of temperature and humidity on these
products, and points to the necessity of proper storage and packaging conditions and to the
necessity of choosing an appropriate retail package. The variety of materials capsulated,
which may have an effect on the gelatin shell, together with the many gelatin formulations
that can be used, makes it imperative that physical standards are established for each product.
General statements relative to the effects of temperature and humidity on soft gelatin capsules
must be confined to a control capsule that contains mineral oil, with a gelatin shell having a
dry glycerin to dry gelatin ratio of about 0.5 to 1 and a water to dry gelatin ratio of 1 to 1, and
that is dried to equilibrium with 20 to 30 % RH at 21 to 24 C, the physical stability of soft
gelatin capsules is associated primarily with the pick-up or loss of water by the capsule shell.
If these are prevented by proper packaging, the above control capsule should have satisfactory
physical stability at temperature ranging from just above freezing to as high as 60 C, for the
unprotected control capsule, low humidities (less than 20 % RH), low temperature (less than 2
C) and high temperatures (greater than 38 C) or combinations of these conditions have only
transient effects. The capsule returns to normal when returned to optimum storage conditions.
As the humidity is increased, with in a reasonable temperature range, the shell of the
unprotected control capsule should pick up moisture in proportion to its glycerin and gelatin
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content.
The total moisture content of the capsule shell, at equilibrium with any given relative
humidity within a reasonable temperature range, should closely approximate the sum of the
moisture content of the glycerin and the gelatin when held separately at the stated conditions.
The effect of temperature and humidity on capsule shell has been illustrated in Table 2.
Table 2: Effect of Temperature and Humidity on Capsule shell
Temperature Humidity Effect on Capsule shell
21-24°C 60% Capsules become softer,tackier and bloated
Greater than 24°C Greater than 45% More rapid and pronounced effects –
unprotected
capsules melt and fuse together
Capsules containing water-soluble or miscible liquid bases may be affected to a greater extent
than oil-based capsules, owing to the residual moisture in the capsule content and to the
dynamic relationship existing between capsule shell and capsule fill during the drying process.
The capsule manufacturers routinely conduct accelerated physical stability tests on all new
capsule products as an integral part of the product development program. The following tests
have proved adequate for determining the effect of the capsule shell content on the gelatin
shell. The tests are strictly relevant to the integrity of the gelatin shell and should not be
confused as stability tests for the active ingredients in the capsule content. The results of such
tests are used as a guide for the reformulation of the capsule content or the capsule shell, or
for the selection of the proper retail package. The test conditions for such accelerated physical
stability tests are shown in table 3.
The capsules at these stations are observed periodically for 2 weeks. Both gross and subtle
effects of the storage conditions on the capsule shell are noted and recorded. The control
capsule should not be affected except at the 80 % RH station, where the capsule would react
as described under the effects of high humidity.
Table 3 Test conditions for accelerated physical stability tests for capsule dosage forms
A Brief overview on Capsule
Test conditions
Observation
80 % RH at room temperature in an open
container.
Capsules are observed periodically for 2 weeks,
both gross and subtle effects of the storage
conditions are noted and recorded. The control
capsule should not be affected
40 C in an open container.
40 C in a closed container (glass bo ttle with
tight screw-cap).
except at the 80% RH station.
8) Packaging and storage of capsules:-
Capsules should be packed in a well-closed glass or plastic containers and stored in a
cool place. These type of containers have advantage over cardboard boxes that they are more
convenient to handle and transport and protect the capsules from moisture and dust. To
prevent the capsules from rattling a tuft of cotton is placed over and under the capsules in the
vials. In vials containing very hygroscopic capsules a packet-containing desiccant like silica
gel or anhydrous calcium chloride may be placed to prevent the absorption of excessive
moisture by the capsules. Now a days capsules are strip packaged which provide sanitary
handling of medicines, ease in counting and identification.
Empty gelatin capsules should be stored at room temperature at constant humidity.
High humidity may cause softening of the capsules and low humidity may cause drying and
cracking of the capsules. Storage of capsules in glass containers will provide protection not
only from extreme humidity but also from dust.
Storage of filled capsules is dependent on the characteristics of the drugs they contain.
Semisolid filled hard gelatin capsules should be stored away from excessive heat, which may
cause a softening or melting of the contents.
9) Capsule Administration :-
Capsules of the size No. 5 to No. 0 generally are not too difficult to swallow. Many
patients may have difficulty swallowing the No. 00 and No. 000 capsules. If this occurs, the
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patient may be advised to place the capsule on the back of the tongue before drinking a liquid,
or to place the capsule in warm water for a few seconds prior to taking to make it slide over
mucous membranes easily. The pharmacist may suggest an alterative dosage form, e.g.
smaller capsules or a liquid or rectal preparation.
Special types of hard gelatin capsules
Altered Release: The rate of release of capsule contents can be varied according to the nature
ofthe drug and the capsule excipients. If the drug is water-soluble and a fast release is desired,
the excipients should be hydrophilic and neutral. If a slow release of water-soluble drug is
desired, hydrophobic excipients will reduce the rate of drug dissolution. If the drug is
insoluble in water, hydrophilic excipients will provide a faster release; hydrophobic and
neutral excipients will slow its release. A very rapid release of the capsule contents can be
obtained by piercing holes in the capsule to allow faster penetration by fluids in the
gastrointestinal tract, or by adding a small quantity of sodium bicarbonate and citric acid to
assist in opening the capsule by the evolution of carbon dioxide.
About 0.1 to 1% of sodium lauryl sulfate may be added to enhance the penetration of water
into the capsule and speed dissolution. If slower release of the active drug is desired, it can be
mixed with various excipients, such as cellulose polymers (methylcellulose) or sodium
alginate. In general, the rate of release is delayed as the proportion of polymer or alginate is
increased relative to water soluble ingredients, such as lactose. It should be mentioned that it
is difficult to predict the exact release profile for a drug and to obtain consistent results from
batch to batch. Further, reliable, consistent blood levels and duration of action can only be
proved with controlled bioequivalence studies. In addition, many medications exhibit narrow
therapeutic indices as the toxic and therapeutic doses are very close. Therefore,
extemporaneous attempts to alter release rates to this extent should be avoided.
Coating capsules: Coatings have been applied extemporaneously to enhance appearance and
conceal taste, as well as to prevent release of the medication in the stomach (enteric coated
products). Most coating of capsules requires considerable formulation skill and quality control
equipment found in manufacturing facilities. Capsules can be coated to delay the release of
the active drug until it reaches a selected portion of the gastrointestinal tract. Materials found
suitable include stearic acid, shellac, casein, cellulose acetate phthalate and natural and
synthetic waxes; the basis of their use is their acid insolubility but alkaline solubility. Many of
the newer coating materials are time:erosion-dependent rather than acid:base-dependent, i.e.
they erode over time on exposure to gastrointestinal contents rather than over a pH gradient.
There are, in addition, a number of newer materials with predictable pH solubility profiles.
a. Enteric-coated capsules – enteric-coated capsules resist disintegration in the stomach but
break up in the intestine. They have largely been superseded by enteric-coated tablets. Types
of coating used commercially include cellulose acetate phthalate and mixtures of waxes and
fatty acids and/or their esters. Enteric coating may be given to following categories of drugs –
• For substances that irritate the gastric mucosa or are destroyed by the gastric juice,
and for medicaments, such as amoebicides and anthelmintics that are intended to act in the
intestine.
A Brief overview on Capsule
• Which interfere with digestion e.g. tannins, silver nitrate and other salts of heavy
metals.
• Which are required to produce delayed action of the drug.
In general, the application of a coating requires skill and additional equipment. A general
coating can be applied but should probably only be used in medications that would not be of a
critical nature. In many cases, experience must be developed for specific formulations
depending upon the requests of the physicians and the needs of the individual patients.
Several coating methods may be used and are described as follows:
1.Beaker-flask coating - Place a very small quantity of the coating material in the flask
and gently heat until it has melted. Add a few capsules, remove from the heat and rotate the
flask to start application of the coating. Periodically add a few more drops of melted coating
material with continued rotation. The addition of very small quantities is all that is required to
keep the capsules from sticking together and clumping.
2.Dipping - Heat the coating material in a beaker at the lowest feasible temperature.
Individual capsules can be dipped using tweezers, allowing the coating to cool and repeating
the process until a sufficient layer has been developed.
3.Spraying - An alcoholic or ethereal solution of the coating material is prepared and
placed in a small sprayer (a model airplane paint sprayer works well). The capsules are placed
on a screen in a well-ventilated area. The solution of coating material is applied in very thin
coats with sufficient time allowed for drying between coats (A hair dryer may be used
cautiously for this step). The process is repeated until a sufficient layer has been developed.
Sustained release capsules– the traditional method of taking a dose three or four times a day
leads to periods of excess and deficiency in blood concentration of the medicament. One way
of correcting this and, at the same time, reducing the number of doses per day, is to administer
a capsule containing numerous coated pellets that release the drug successively over a long
period.
The finely powdered drug is first converted into pellets, usually by attaching it to sugar
granules with an adhesive. The pellets are then treated with protective coatings that delay
release of the drug, each batch receiving a different thickness. The batches are mixed
thoroughly and suitable doses are filled into capsules. For example, a mixture might contain
30 percent of uncoated pellets, for immediate release of drug, 30 percent each of coated
pellets that release at 4 hours and 8 hours, and 10 percent of neutral pellets, used solely to fill
the capsule. Each batch may be colored differently to simplify identification and facilitate
control of mixing.
Liquid filled hard gelatin capsules
It is generally accepted that many of today’s NCE’s (New Chemical Entities) are poorly
water soluble and the classical methods, such as reduction in particle size are no longer
adequate to achieve satisfactory drug adsorption from a solid oral dosage form. One of the
most promising strategies to deliver these insoluble compounds is using dissolved systems
like using lipids, liquids or semi-solids to formulate new products. Twp piece hard shell
capsules are one of the most logical approaches when choosing the best dosage form to
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deliver these new liquid formulations.
The new technology of packaging liquids in hard gelatin capsules is considered a major
breakthrough. It can make a significant contribution to the development of efficacious
pharmaceutical products by providing the flexibility to rapidly develop and test in-house
formulations when only small quantities of drug substance is available. The process can be
scaled-up and also kept in-house similar to the operations of tabletting or powder/pellet filling
of hard gelatin capsules.
Capsules for packing of Ophthalmic ointments
It is very important that the ophthalmic ointments should be sterile and free from irritant
effect. Therefore they must be packed in such a manner that the product remains sterile until
whole of it is used up. The best method to keep the preparation free from contamination
during use is to pack it in single dose containers. Now a days soft gelatin capsules are very
commonly used for filling ophthalmic ointments. These capsules are meant for single
application to the eye. Just before application, the capsule is punctured with a sterile needle,
the contents instilled into the eye and the shell discarded.
10) Recent updates in Capsule technology :-
A) New products by Capsugel:
1.Capsugel has introduced Oceancaps capsules, these capsules made from all
natural fish gelatin derived from farm-raised fish, they have the same characteristics as
traditional gelatin capsules, including appearance, machinability, mechanical properties,
hygroscopic and oxygen properties, chemical stability, and versatility. Plus, they are odorless
and tasteless
2.Licaps new 000 size capsules are ideal for maximizing liquid dosage with a fill
capacity of 1000mg to 1400mg depending on the density of the liquid fill material. This two-
piece capsules has been specially designed to be sealed for secure containment of liquids and
semi- solids without banding. Available in both gelatin and HPMC (Hydroxypropyl
Methylcellulose) capsules they are available in a variety of colors to meet your specific needs.
A Brief overview on Capsule
Conclusion
The popularity of capsule is due to its properties & benefits over tablet dosage forms. To
bitter coating of taste & unpleasant odour drug is costly. While filling such drugs in hard
gelatin capsules could mask unpleasant taste, odour & cost effective technique which gives
added advantage of fast onset of action.
References
1) Pharmaceutics – The Science of Dosage form Design by M.E.Aulton,2
nd
Edition.
2) The Theory and Practice of Industrial Pharmacy by Leon Lachman.
3) Website – ww w
.c a p
s ug
e l . com
4) Website – www.liquidcapsules.com
5) Textbook of Pharmaceutics by Bentley, 8
th
Edition.
6) Encycloprdia of Pharmaceutical Technology, Volume – 2.
7) Remington – The Science and Practice of Pharmacy, 20th Edition, Volume – 1.
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