Capsule:

1.A small container

2.A soluble gelatin case containing a dose of medicine
3.A solid oral dosage form consisting of a shell and a filling.

The shell is composed of a single sealed enclosure, or two halves that fit
together and which are sometimes sealed with a band. Capsule shells may
be made from gelatin, starch, or cellulose, or other suitable materials.

There are two forms of capsules,

1.Hard capsules
2.Soft capsules.
Hard capsules are for powders or semi-solid preparations and soft capsules
for liquids.

Hard capsules were invented in 1833 in France. They were (and are today)
made of gelatin and consist of two parts, a body and a cap. While soft
gelatin capsule is single sealed enclosure.
CAPSULE
Gelatin:
Gelatin is a protein produced by partial hydrolysis of collagen extracted
from the bones, connective tissues, organs, skin and some intestines of
animals such as the domesticated cattle, and horses . It is insoluble in
water and is solubilized by hydrolysis. The raw materials used for its
manufacture are obtained mainly from bovine bones or porcine skins. It is
insoluble in water and is solubilized by hydrolysis. The raw materials used
for its manufacture are obtained mainly from bovine bones or porcine
skins. In addition to gelatin, the shells may contain colorants, opacifiers,
and preservatives (often parabens esters)

The manufacturing processes of gelatin consists of three main stages:

1.Pretreatments to make the raw materials ready for the main extraction
step and to remove impurities which may have negative effects on
physicochemical properties of the final gelatin product.
2.The main extraction step, which is usually done with hot water or dilute
acid solutions as a multistage extraction to hydrolyze collagen into gelatin.
3.The refining and recovering treatments including filtration, clarification,
evaporation, sterilization, drying, grinding, and sifting to remove the water
from the gelatin solution, to blend the gelatin extracted, and to obtain dried,
blended and ground final gelatin.
Types of Gelatin
There are two types of gelatin
1. Type A Gelatin 2. Type B Gelatin

Type A gelatin is derived from acid treated precursor and have the
isoelectric pH of 9.
Type B gelatin is derived from acid treated precursor and have the
isoelectric pH of 4.7
Type A normally originates from porcine skin while B is usually derived from
animal bones. Gelatin can comprise a mixture of both types in order to
optimize desired characteristics, with bone gelatin imparting
firmness while porcine skin gelatin provides plasticity.
Gelatin is an ideal material because it is edible, soluble at body
temperature, forms strong thin films and undergoes a gelation process at
temperatures just above ambient.
The walls of gelatin capsules are homogenous and very robust, and can
readily withstand the mechanical stresses of the filling and packaging
operations. The
main draw back in the use of gelatin is that it contains water, which acts as
a plasticizer to the film. Their properties will change if they are not stored
properly,
and when water is lost, they become brittle and thus are not suitable for
hygroscopic formulations. Moisture labile substances cannot be filled into
them.
Gelatin capsules are manufactured by a dipping process. The process
starts by the preparation of a concentrated solution of gelatin or other
suitable polymer in hot demineralized water. This solution is subjected to a
low pressure to remove entrapped air bubbles. Small portion of this
solution are taken.To this are added colorants, either solutions of soluble
dyes or suspensions of pigments, preservatives, process aids, such as
disodium lauryl sulfate solution, and water to adjust the viscosity. The final
solution has a concentration of 25–30 wt% of gelatin.

This solution is then delivered to the capsule-manufacturing machine. The

manufacturing machines are housed in rooms supplied with filtered air,
conditioned to 40–45% relative humidity and 22–25C. The most commonly
used machines are approximately 12m long and 3m high and are divided
down the midline into two parts that are mirror images of each other. The
caps are made on the left side and the bodies on the right side of the
machine. The gelatin solutions are held in temperature-controlled, jacketed
hoppers. From there they are fed to the capsule forming container,
variously known as a dip pan or dip pot.
This is a stainless steel-jacketed vessel that is oblong with a box in the
center. The gelatin solution is pumped into the box and overflows the edge,
thus maintaining a constant height. The stainless steel mold pins are
mounted in a row of 30 on steel bars. Sets of bars are held in a device
operated by a cam, which raises and lowers them. The mold pins, which
are at 22C, are lowered into the gelatin solution, which is at 50–55C. The
gelatin immediately gels on the mold. The molds are slowly raised, and, as
they do, the excess gelatin runs off . The quantity picked up by the mold is
proportional to the viscosity. The higher the viscosity of the gelatin solution,
the more the gelatin that is picked up. Thus, the viscosity of the solution is
used to control the thickness of the gelatin film. As the mold breaks the
surface, a blob of gelatin forms on the end of the mold. The sets of bars are
transferred from the bottom to the top level of the machine and, as they do
so, the bars are rotated to spread the film evenly over the end of the mold
pin.
The gelatin film is completely set by the time. Sets of bars are grouped
together and mechanically transferred through a series of drying kilns. In
these, air at controlled temperature and humidity is blown over them.
The dried gelatin films are removed from the mold pins and cut to the
correct lengths, and the cap and body pieces are joined together.
Dip pan, capsule shell formation
Method of production
 Capsule Sizes with capacity

TABLE 5 Capsule Size and Corresponding Volume or Weight of Fill

Size Volume (mL) Fill weight a (g)
000 1.37 1.096
00 0.95 0.760
0 0.68 0.544
1 0.50 0.400
2 0.37 0.296
3 0.30 0.240
4 0.21 0.168
5 0.13 0.104

Assumes a powder density of 0.8 g/cm 3 .

Advantages of capsules
 Bioavailability Enhancement and Stability.
 Versatile - oral, rectal, vaginal and topical applications.
 To deliver powders.
 Superior means of delivery liquids.
 Masking of bad odors and tastes.
 Precise dosage control.
 Reduces potential of cross contamination of powders in production.
 Protects Contents from contamination, oxidation and light.
 Patient Preference Studies - Demonstrate appeal to consumers.
 Available in wide ranges of Colours, Shapes and Sizes.
 Outstanding Visual appeal.
 Easy to swallow.
 Patent protection and Line Extension.
 Tamper-evident / tamper resistant characteristics.
 High accuracy for Lower Dose of active ingredients.
 High degree of product elegance & differentiation for a Marketing
Edge
1.After capsules 2.Open capsules once 3.Eject the unopened
arranged and oriented, again to ensure the capsule and the faulty
put capsule into the capsule to be opened. into a collection box.
mold and open it by
vacuum.

4.&5.Both Stations are reserved for pellet or granule filling

6.Put dosing tube into 7.Reclaim the powder 8.Join capsules together
powder plate. The which not being filled into by upper and lower
powder will be the capsules from the closing pins.
compressed into slug. collector.
Then eject the powder
slug into the open
capsule.
9.Eject the filled capsule into the 10.Clean the residue powder
collection container. attached to cap and body mold by
suction for next cycle use.
Company Model Rated Out put/Hr Remarks
2000/15 40,000
Formatic 200/30 80,000 Dosator filling
2000/60 160,000
Zanasi LZ-64 4000
AZ-20 9000-20,000
BZ-40 30,000
BZ-72 60,000
BZ-40, 70, Z-5000-R1, Z-5000-
BZ-110 110,000 R2 and Z-5000-R3 can handle
BZ-115 115,000 powder, pellets and tablets
Z-5000-R1 70,000
Z-5000-R2 110,000
Z-5000-R3 150,000
Mecofar MT12, MT13/1,MT13/2 35,000, 5000 and 10,00
mG2 G36/4, G36/2, G-36, G37N, 9000, 18,000, 36,000,
can handle powder, pellets
G38 96,000 and 60,000
Osaka R-180 70,000-165,000
Perry Accofil 60,000 Powder feeding through suction
Soft Gelatin Capsules
The soft gelatin capsule is composed of
1.Gelatin
2.Plasticizer
3.Water
4.Other ingredients (Preservative, colorants, opacifiers, flavours, sugar,
acids and medicaments).
The most common plasticizer used are sorbitol, glycerin or combination of
these. The common ratio of plasticizer to gelatin (dry basis) is 0.4-0.8 :1.
The gelatin must be checked for specification other than pharmacopoeia,
these include bloom strength, viscosity and iron content
1.Bloom or gel strength: it is the measure of cohesive strength of the
cross linking that occurs between gelatin molecule and is proportional to
the molecular weigh of gelatin. It is determined by measuring the weight in
grams required to move plastic plunger of 0.5 inches in diameter 4 mm into
a 6.66% gelatin solution held at 10oC for 17 hours. The range for bloom
strength is 150-250 g.
2. Viscosity: it is determined using 6.66% aqueous gelatin solution at
60oC. The range for viscosity is 25-45 millipoise.
3.Iron content: gelatin used for soft gelatin capsule should not contain
iron more than 15 ppm.
The most common size for human is oblong 20 minims, oval 16 minims
and round 9 minims
Filling Equipment
• Plate
• Rotary die
• Reciprocating die
• Accogel