CAPSULES

CAPSULES
 Capsules are solid dosage forms in which medicinal agents and/or inert
substances are enclosed in a small shell of gelatin.
 Gelatin capsule shells may be hard or soft, depending on their composition.
 Most filled capsules are intended to be swallowed whole.
 However, it is fairly common in hospitals and extended care facilities for a
caregiver to open capsules or crush tablets to mix with food or drink,
especially for children or other patients unable to swallow solid dosage
forms. This should be done only with the concurrence of the pharmacist,
since the drug release characteristics of certain dosage forms can be altered
and can adversely affect the patient’s welfare.
 Advantages of Capsules
 They mask the taste and odour of unpleasant drugs and are easily administered.
 They are attractive in appearance.
 They are slippery when moist and hence, easy to swallow with water.
 They require less excipients for manufacture than tablets.
 Their shells are inert and are quickly digested by GIT.
 They are easy to handle and carry.
 They are economical and easily available.
 They have better shelf life and bioavailability than tablets.
 They can be made opaque by treating with titanium dioxide and can be used for
photosensitive drugs.
 No Measuring device is needed for their administration.
 Disadvantages:
 Hygroscopicdrugs are not suitable to be filled in capsules as
they absorb moisture from shell and make them brittle.
 Concentrated solutions which require previous dilution
cannot be filled in capsules as they lead to irritation of
stomach.
 Hard gelatin capsules

 Hard gelatin capsules consist of two parts, cap and body.

 The empty capsule shells are made of gelatin, sugar, and water.
 As such, they can be clear, colorless, and essentially tasteless.
 They may be colored with various FD&C and D&C dyes and made opaque by adding
agents such as titanium dioxide.
 Most commercially available medicated capsules contain combinations of colorants
and opaquants to make them distinctive, many with caps and bodies of different
colors.
 Hard gelatin capsules

 Hard gelatin capsule shells are used in most commercial medicated

capsules
 They are also commonly employed in clinical drug trials to compare
the effects of an investigational drug with those of another drug
product or placebo.
 The community pharmacist also uses hard gelatin capsules in the
extemporaneous compounding of prescriptions. The empty capsule
shells are made of gelatin, sugar, and water.
 Inserting tablets or small capsules into capsules is sometimes useful to
separate chemically incompatible agents or to add premeasured
amounts of potent drug substances. Rather than weighing a potent
drug, a pharmacist may choose to insert a prefabricated tablet of the
desired strength in each capsule.
 Hard Gelatin Capsules
 Normally, hard gelatin capsules contain 13% to 16% of moisture.
 However, if stored in high humidity, additional moisture is absorbed and capsules lose
their rigid shape.
 In extreme dryness, some of the moisture normally present in the gelatin capsules is
lost, and the capsules may become brittle.
 Therefore, it is desirable to maintain hard gelatin capsules in an environment free
from excessive humidity or dryness. Many capsules are packaged along with a small
packet of a desiccant like dried silica gel, clay, and activated charcoal.
 Gelatin

 Gelatin is obtained by the partial hydrolysis of collagen obtained from the skin,
white connective tissue, and bones of animals.
 In commerce, it is available in the form of a fine powder, a coarse powder, shreds,
flakes, or sheets.
 Gelatin is stable in air when dry but is subject to microbial decomposition when it
becomes moist.
 Gelatin softens in cold water absorbing up to 10 times its weight of water. Some
patients prefer to swallow a capsule wetted with water or saliva.
 Gelatin is soluble in hot water and in warm gastric fluid; a gelatin capsule rapidly
dissolves and exposes its contents. Gelatin, being a protein, is digested by
proteolytic enzymes and absorbed.
Disadvantage of Hard Gelatin Capsules
 Gelatin capsules are unsuitable for aqueous liquids because water
softens gelatin and distorts the capsules, resulting in leakage of the
contents. soft gelatin capsules are used for this purpose.
 THE MANUFACTURE OF HARD
GELATIN CAPSULE SHELLS
 Hard gelatin capsule shells are manufactured in two sections, the
capsule body and a shorter cap. The two parts overlap when joined,
with the cap fitting snugly over the open end of the capsule body.
 The shells are produced industrially by the mechanical dipping of pins
or pegs of the desired shape and diameter into a temperature controlled
reservoir of melted gelatin mixture.
 About 500 pegs (made of manganese bronze) of the desired shape and
diameter are affixed to plates.
 Each plate is mechanically lowered into the gelatin bath, the pegs
submerged to the desired depth and maintained for the desired period.
 Then the plate and the pegs are slowly lifted from the bath and the gelatin is
dried by a gentle flow of temperature- and humidity-controlled air.
 When dried, each capsule part is trimmed mechanically to the proper length
and removed from the pegs.
 Then capsule bodies and caps are joined together.
 The pegs on which the caps are formed are slightly larger in diameter than
the pegs on which the bodies are formed
 manufacturer also may prepare distinctivelooking capsules by altering the
usual rounded shape of the capsule-making pegs. By tapering the end of the
body-producing peg while leaving the cap-making peg rounded, one
manufacturer prepares capsules differentiated from those of other
manufacturers
Capsules being dipped for coloring on automated capsule-
making equipment. (Courtesy of Shinogi Qualicaps.)
1.Tapered rim to avoid telescoping (CONI-SNAP™)

2. Grooves which lock the two halves together once the

capsule has been filled (SNAP-FIT™ principle)

3. Indentations to prevent premature opening

 CAPSULE SIZES:
 Empty gelatin capsules are manufactured in various lengths, diameters, and
capacities.
 The size selected for use is determined by the amount of fill material to be
encapsulated.
 The density and compressibility of the fill will largely determine to what extent it may
be packed into a capsule shell.
 For human use, empty capsules ranging in size from 000 (the largest) to 5 (the
smallest) are commercially available.
 Larger capsules are available for veterinary use.
 PREPARATION OF FILLED HARD
GELATIN CAPSULES:
 The large-scale or small-scale preparation of filled hard gelatin
capsules is divided into the following general steps.
1. Developing and preparing the formulation and selecting the capsule
size
2. Filling the capsule shells
3. Capsule sealing (optional)
4. Cleaning and polishing the filled capsules
 1-DEVELOPING THE FORMULATION
AND SELECTING THE CAPSULE SIZE
 In developing a capsule formulation, the goal is to prepare a capsule with accurate dosage, good bioavailability,
ease of filling and production, stability, and elegance.
 In dry formulations, the active and inactive components must be blended thoroughly to ensure a uniform
powder mix for the fill. To achieve uniform drug distribution, density and particle size of the drug and nondrug
components are similar. When necessary, particle size may be reduced by milling to produce particles ranging
from about 50 to 1,000 μm.
 A diluent or filler may be added to the formulation to produce the proper capsule fill volume. Lactose,
microcrystalline cellulose, and starch are commonly used for this purpose.
 Disintegrants are frequently included in a capsule formulation to assist the breakup and distribution of the
capsule’s contents in the stomach e.g., pregelatinized starch, croscarmellose, and sodium starch glycolate.
 The addition of a lubricant or glidant such as fumed silicon dioxide, magnesium stearate, calcium stearate,
stearic acid, or talc (about 0.25% to 1%) to the powder mix enhances flow properties.
 A surface-active agent, such as sodium lauryl sulfate, is used to facilitate wetting by the gastrointestinal fluids to
overcome the problem.
 The selection of the capsule size for a commercial product is done during product
development. Hard gelatin capsules are used to encapsulate about 65 mg to 1 g of powdered
material.
 A properly filled capsule should have its body filled with the drug mixture, not the cap. The
cap is intended to fit snugly over the body to retain the contents.
 An easy method to select the proper capsule is
1. to weigh the ingredients for the required number of capsules to be prepared.
2. Place the powders in a graduated cylinder and obtain the volume occupied by the powders.
3. Divide the volume by the number of capsules to be prepared and this provides the volume
that will be occupied by the powder for each capsule.
4. Compare this volume (in mls) with the appropriate line of Table and select the size that will
accommodate the powder.
 If the capsule is too large, simply multiply the capsule size in volume by the number of
capsules to be prepared to obtain the final volume of the powder that is required. Then add
additional diluent to the graduated cylinder containing the other powders to the mark
indicated for the total volume of powder required.
 For documentation, weigh the total powder blend and subtract the initial quantities that
were weighed, and the quantity of additional diluent that was added will be obtained.
 2-FILLING HARD CAPSULE SHELLS:
 When filling a small number of capsules in the pharmacy, the pharmacist
may use the punch method.
 The pharmacist takes the precise number of empty capsules to be filled from
the stock container.
 The powder to be encapsulated is placed on a sheet of clean paper or on a
glass or porcelain plate.
 Using the spatula, the powder mix is formed into a cake having a depth of
approximately one-fourth to one-third the length of the capsule body.
 Then an empty capsule body is held between the thumb and forefinger and
punched vertically into the powder cake repeatedly until filled.
 Some pharmacists wear surgical gloves or latex finger cots to avoid handling
the capsules with bare fingers.
 Because the amount of powder packed into a capsule depends on the degree
of compression, the pharmacist should punch each capsule in the same
 For non-potent drugs, first capsule is weighed and then periodical checking is done but for potent
drugs, each capsule is to be weighed after filling to ensure dose accuracy.
 Granular material may be poured into each capsule from the powder paper on which it is
weighed.
 The various hand-operated filling machine have capacities ranging from 24 to 300 capsules and,
when efficiently operated, are capable of producing about 200 to 2,000 capsules per hour.
 Machines developed for industrial use automatically separate the caps from empty capsules, fill
the bodies, scrape off the excess powder, replace the caps, seal the capsules as desired, and clean
the outside of the filled capsules at up to 165,000 capsules per hour.
 The Feton capsule-fi lling machine. A. With
empty capsules in the loader tray, the tray
placed on top of the fi ller unit. B. The loader
inserts the capsules into the fi lling unit and is
removed, and the top plate is lifted to
separate the caps from the bodies. C. The
powder is placed on the unit and the capsule
bodies are fi lled. D. The top plate is returned
to the unit and the caps are placed on fi lled
capsule bodies. (Courtesy of Chemical and
Pharmaceutical Industry Company.)
 The Feton capsule-fi lling machine. A. With empty capsules in the loader tray, the tray
placed on top of the filler unit. B. The loader inserts the capsules into the fi lling unit
and is removed, and the top plate is lifted to separate the caps from the bodies. C. The
powder is placed on the unit and the capsule bodies are fi lled. D. The top plate is
returned to the unit and the caps are placed on fi lled capsule bodies. (Courtesy of
Chemical and Pharmaceutical Industry Company.)
 3-CAPSULE SEALING
 Manufacturer makes distinctive-looking capsules by sealing them with a colored band of gelatin.
Capsules may also be sealed through a heat-welding process that fuses the capsule cap to the
body. The process results in a distinctive ring around the capsule where heat welded.
 Still another process uses a liquid wetting agent that lowers the melting point in the contact areas
of the capsule’s cap and body and then thermally bonds the two parts using low temperatures
(40°C–45°C).
 Extemporaneously prepared capsules may be sealed by lightly coating the inner surface of the
cap with a warm gelatin solution immediately prior to placement on the filled capsule body.
 4-CLEANING AND POLISHING CAPSULES:

 On a small scale, capsules may be cleaned individually or in small

numbers by rubbing them with a clean gauze or cloth.
 On a large scale, many capsule filling machines are affixed with a
cleaning vacuum that removes any extraneous material from the
capsules as they exit the equipment.
 For polishing, pan polishing like Accela Cota pan coating machines may
be used.
 Soft gelatin Capsules

 Soft gelatin capsules are made of gelatin to which plasticizer like glycerin or a polyhydric alcohol
such as sorbitol has been added.
 Soft gelatin capsules, which contain more moisture than hard capsules, may have a preservative,
such as methylparaben and/or propylparaben, to retard microbial growth.
 Soft gelatin capsules may be oblong, oval, or round. They may be single colored or two-toned and
may be imprinted with identifying markings.
 As with hard gelatin capsules, they may be prepared with opaquants to reduce transparency and
render characteristic features to the capsule shell.
 Applications of Soft gelatin Capsules

 Soft gelatin capsules are used to encapsulate and hermetically seal

liquids, suspensions, pasty materials, dry powders, and even preformed
tablets.
 Soft gelatin capsules are available as suppositories.
 They have various applications for cosmetic purpose as they enclose
bath oils, perfumes, vitamins etc.
 Preparation of Soft gelatin Capsules

 Soft gelatin capsules may be prepared by the plate process, using a set of
molds to form the capsules, or by the more efficient and productive
rotary or reciprocating die processes by which they are produced, filled,
and sealed in a continuous operation.
 1- Plate process:

 By the plate process, a warm sheet of plain or colored gelatin is

placed on the bottom plate of the mold and the medication-
containing liquid is evenly poured on it.
 Then a second sheet of gelatin is carefully placed on top of the
medication and the top plate of the mold is put into place.
 Pressure is then applied to the mold to form, fill, and seal the
capsules simultaneously.
 The capsules are removed and washed with a solvent harmless
to the capsules.
 2- Rotary die process:
 Most soft gelatin capsules are prepared by the rotary die process, a
method developed in 1933 by Robert P. Scherer.
 By 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.
 At the same time, metered fill material is injected between the ribbons
precisely at the moment that the dies form pockets of the gelatin
ribbons.
 These pockets of fill-containing gelatin are sealed by pressure and heat
and then severed from the ribbon.
 Use of ribbons of two different colors results in bicolored capsules.
Storage and dispensing of capsules:

 Depending on the item, the container may be required to be

tight, well-closed, light resistant, and/or all of these.
 Capsules should be stored in tightly capped containers in a cool,
dry place.
 Various strip packings or amber coloured glass bottles are used
for storing capsules.