Transcript Lecture 15. Capsules production

Capsules production
Plan
1.
2.
3.
4.
5.
Characteristic of capsules as dosage forms.
Manufacturing of Hard Gelatin Shells
(capsules).
Hard-Gelatin Capsule filling.
Soft-Gelatin Capsules.
Microcapsules.
► Capsules
are solid dosage forms with hard
or soft shells. They are of various shapes
and sizes, and contain a single dose of one
or more active ingredients. They are
intended for oral administration.
► In capsules the drug is enclosed within hard
or soft shell.
Capsule shells are made of gelatine or
other substances, the consistency of which
may be modified by the addition of
substances such as glycerol or sorbitol.
The shell should disintegrate in the
presence of digestive fluids so that the
contents are released.
The contents should not cause
deterioration of the shell.
Excipients for the Capsule shells
production:
diluents,
solvents,
surface-active substances,
opaque fillers,
antimicrobial agents,
sweeteners,
colouring matter,
flavouring substances,
disintegrating agents,
glidants,
lubricants,
substances capable of modifying the behaviour of the active
ingredient(s) in the gastrointestinal tract.
Categories of capsules
hard capsules;
soft capsules (softgels);
modified-release capsules:
delayed-release capsules
(gastroresistant / enteric capsules)
2. sustained-release capsules
(extended-/prolonged release capsules).
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1.
Type of capsules depend on
plasticizer content
and technological principle
1. Hard-Shell Gelatin Capsules;
2. Soft- Gelatin Capsules
(softgels);
Soft gelatin capsules (softgels) are hermetically
sealed one-piece capsules containing a liquid or
a semisolid fill.
Soft capsules are usually formed, filled, and
sealed at the one operation.
Advantages
of soft-gelatin capsules
1.
2.
3.
4.
5.
Improved bioavailability, as the drug is presented in a
solubilized form.
Enhanced drug stability.
Consumer preference regarding ease of swallowing,
convenience, and taste can improve compliance.
Offer opportunities for product differentiation via colour,
shape, and size and product line extension.
The softgels can be enteric coated for delayed release.
They are popular for pharmaceuticals, cosmetics, and
nutritional products.
 Hard capsules have shells consisting of two
prefabricated cylindrical sections that fit
together.
 One end of each section is rounded and closed,
and the other is open. The contents of hard
capsules are usually in solid form (powder or
granules).
In the manufacture of capsules,
measures are taken to:
 ensure that the active ingredient(s) when
present in solid state form have appropriate
solid-state properties such as particle-size
distribution and polymorphic form;
 ensure that mixing with excipients is carried
out in a manner that ensures homogeneity;
 minimize the degradation of the active
ingredient(s);
 minimize the risk of microbial contamination;
 minimize the risk of cross contamination.
Stages of capsules production:
1.
2.
3.
4.
Preparing of gelatin 1. Preparing of gelatin
solutions.
solutions.
Preparing of gelatin 2. Preparing and filling
shells.
of soft-gelatin
capsules.
Hard-gelatin
capsule filling.
Packing and
3. Packing and
labeling.
labeling.
Methods obtaining
of gelatin solutions
Obtaining
of gelatin solutions
with stage of
swelling
Obtaining
of gelatin solutions
without stage of
swelling
HJ Series Gelatin Melting
Tank
Obtaining of gelatin solutions
with stage of swelling
1.
2.
3.
4.
5.
Swelling of gelatin in the cold water (15 - 18 °C,
1.5 - 2 hours).
Dissolving of gelatin.
Adding of preservatives, plasticizers and others
excipients.
Removing of air bubbles from the gelatin solution
by the vacuum.
Stabilization of gelatin solution (45-60 °C).
Obtaining of gelatin solutions
without stage of swelling
1.
2.
3.
4.
5.
Heating of the purified water (70-75 °C).
Dissolution of preservatives, plasticizers and
others excipients in the water.
Dissolution of the gelatin.
Removing of air bubbles from the gelatin
solution by a vacuum.
Stabilization of the gelatin solution (45-60 °C).
Methods of
softgels production
Droplets method
Compressing
method
Droplets method
1. Hoper with
medicines substance
2. Container with
medicines substance
3. Container with
gelatin solution
4. Conical nozzle
5. Pulsater
6. Tube for the cooling
7. Container with
Vaseline oil
Characteristic of the
Droplets method
It is based on formation of spherical
gelatinous drops filled with a solution or
suspension of medicinal substance at the
simultaneous dosing of the medicinal
substance.
Then the cooling of heated gelatinous mass
in cool liquid petrolatum is carried out.
As the result joinless spherical gelatious
capsule with elastic shell are formed.
Droplets method
1. Hoper with
medicines substance
2. Container with
medicines substance
3. Container with
gelatin solution
4. Conical nozzle
5. Pulsater
6. Tube for the cooling
7. Container with
Vaseline oil
RG2-200 250 300 Series Soft
Gelatin Encapsulation Machine
• For volume-production,
increase the utilization
ration of gelatin skin;
• convey gelatin skin with
a plane surface more
steady running
condition;
• oil saving;
• suitable for volumeproduction, continually
for 24 hour.
(Huizhou Pingfang
pharmaceutical machinery
co. ltd.)
Compressing method
Preparing of an initial gelatinous
tape, placing it into metal plates
and rolls having deepening holes
resembling half of the capsules.
While heating gelatin fills this
mould. Drug is fed into a hollow
in a gelatinous tape, then this
half of a capsule is joined with
another one formed and filled in
the same way. Obtained capsules
have a horizontal weld.
Compressing (rotate die)
method
The glycerol – gelatin solution is heated
and pumped onto two chilled drums-1
to form two separate ribbons-2, which
form each half of the softgel.
The ribbons are lubricated and fed into
the filling machine, forcing the gelatin
to adopt the contours of the die.
The fill-4 is manufactured in a separate
process and pumped in, and the
softgels are sealed by the application
of heat and pressure.
Once cut from the ribbon (5), they are
tumble - dried and conditioned at
20 % relative humidity.
Hard capsules production
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To manufacture the shells, pairs of molds, for
the body and the cap, are dipped into an
aqueous gelatin solution (25 – 30 % w/w),
which is maintained at about 50 °C in a
jacketed heating pan.
As the pins are withdrawn, they are rotated to
distribute the gelatin evenly and blasted with
cool air to set the film.
Drying is carried out by passing dry air over
the shell as heating temperatures are limited
due to the low melting point of gelatin.
The two parts are removed from the pins,
trimmed, and joined using a prelock
mechanism.
SFR 901 FS6/7

In this model of capsule
making machine,
dipping action, transfer
along upper deck,
transfer from upper to
lower deck and transfer
from lower deck to
table are all performed
by high precision
programmable servo
motors combined with
precision ball screws
Hard - Gelatin Capsule Filling
Powders and granules are the most common
filling materials for hard - shell gelatin
capsules, although pellets, tablets, pastes,
oily liquids, and nonaqueous solutions and
suspensions have been used.
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Filling machines are differentiated by the way
they measure the dose of material and range
in capacity from bench - top to high - output,
industrial, fully automated machines.
Hard - Gelatin Capsule Filling
Most automated machinery is of the
independent type and compresses a
controlled amount of powder using a low
compression force (typically 50 – 200 N ) to
form a plug. Most are piston - tamp fillers
and are dosator or dosing disk machines.
The powder is passed over a dosing plate
containing cavities slightly smaller than the
capsule diameter, and powder that falls into
the holes is tamped by a pin to form a plug.
In the dosator method, the plug is formed
within a tube with a movable piston that
controls the dosing volume and applies the
force to form the plug.
 The dose is controlled by the dimensions of
the dosator, the position of the dosator in
the powder bed, and the height of the
powder bed.
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NJP-3000,3500 series automatic
capsule filling machine
It comply with volume-produce.
This machine adopts full sealed
filling and turret parts and easy
to clean,
upper and lower die assemblies
move in one-way, imported
double-lip sealing ring made of
polyurethane and have high
performance,
die assemble cleaning work station
combine blowing and breathing
to ensure no powder in die hole
during high speed running,
there is no absorb device in locking
work station, lubricant be added
timing in transmission work
station.
Modified-release capsules
They are hard or soft capsules in which
the contents or the shell or both contain
excipients or are prepared by special
procedures such as microencapsulation
which, separately or together, are
designed to modify the rate, place or time
of release of the active ingredient(s) in the
gastrointestinal tract.
Sustained-release capsules
(Extended- or Prolonged-release capsules) are
designed to slow the rate of release of the active
ingredient(s) in the gastrointestinal tract.
Delayed-release capsules
(gastro-resistant/enteric capsules) are hard or
soft capsules prepared in such a manner that
either the shell or the contents resist the action of
gastric fluid but release the active ingredient(s) in
the presence of intestinal fluid.
Microcapsule is a small sphere with
a uniform wall around it.

Micro-encapsulation is a process in which
tiny particles or droplets are surrounded by a
coating to give small capsules many useful
properties.
 The material inside the microcapsule is
referred to as the core, internal phase, or fill,
whereas the wall is sometimes called a shell,
coating, or membrane.
 Most microcapsules have diameters between
a few micrometers and a few millimeters.
The reasons for microencapsulation
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In some cases, the core must be isolated from its
surroundings, as in isolating vitamins from the
deteriorating effects of oxygen,
retarding evaporation of a volatile core,
improving the handling properties of a sticky material,
or isolating a reactive core from chemical attack.
In other cases, the objective is not to isolate the core
completely but to control the rate at which it leaves the
microcapsule, as in the controlled release of drugs or
pesticides.
The problem may be as simple as masking the taste or
odor of the core, or as complex as increasing the
selectivity of an adsorption or extraction process.