S02.Techno2.Hard Gelatin Capsule
S02.Techno2.Hard Gelatin Capsule
S02.Techno2.Hard Gelatin Capsule
Definition
| A capsule is an edible package made from gelatin or other suitable
material
t i l and
d fill
filled
d with
ith a d
drug(s)
( ) tto produce
d a unit
it d
dosage, mainly
i l
for oral use.
| Hard gelatin capsules: or two-piece capsules which are composed
of two pieces in the form of cylinders closed at one end. The shorter
piece, called the “cap”, fits over the open end of the longer piece,
called the “body”.
| Hard g
gelatin capsule
p shell contains the following
g
ingredients:
z Gelatin.
z Colourants.
z Wetting agents.
z P
Preservatives.
ti
١
Gelatin
Gelatin
| Gelatin has been used for more than a hundred years in the
manufacture of capsules. Its widespread popularity is probably due
to:
z Safety: it is non toxic, widely used in foodstuffs and
acceptable for use worldwide.
z Solubility: it is readily soluble in biological fluids at body
temperature.
z Film forming properties: it is capable of producing
strong flexible films (Thickness of the wall of a hard
gelatin capsule is about 100μm).
٢
Gelatin
z Ease of processing:
Gelatin
٣
Gelatin
Gelatin
Standard probes for gelatin testing as shown above, are available for
the assessment of Bloom strength/Gel strength.
٤
Colourants
Wetting agent
| According to USNF sodium lauryl sulphate is used at a
level of not more than 0.15% w/w as a wetting agent in
hard gelatin capsule to ensure that the lubricated metal
moulds are uniformly covered when dipped in the gelatin
solution.
o Preservatives !!!
• Preservatives were formerly added to hard capsules as an in-
process aid to prevent microbial contamination
contamination.
• Hard gelatin capsules contain between 13 and 16% w/v of
moisture.
• Because the moisture is strongly bound to the gelatin
molecules, gelatin usually doesn’t support microbial growth.
• Manufacturers operating their plants in compliance with GMP do
not have to include preservatives.
٥
Manufacturing
٦
After mixing in stainless steel
receiving tanks
tanks, the gelatin
solution is transferred to stainless
steel feed tanks.
٧
From the feed tank, the gelatin is
gravity fed to specially
engineered Dipper section.
Here, the capsules are moulded
onto stainless steel Pin Bars
which are dipped
pp into the ggelatin
solution.
٨
In the Automatic section,
capsule halves are
individuallyy stripped
pp from
the Pins.
٩
Capsule quality is monitored
throughout the production process
including size, moisture content,
single
g wall thickness,, and colour.
Properties
1. Capsule Sizes
Eight
g sizes of capsules
p are available. The capacity
p y of each size
varies according to the combination of drugs and their apparent densities.
Capsules are available as clear gelatin capsules or in a variety of colors.
Empty Hard Gelatin Capsule Physical Specifications
Height
Outer or Actual Typical Fill
Size Diamete Locked Volume Weights (mg) 0.70
r (mm) Length (mL) Powder Density
(mm)
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
١٠
Capsule Sizes
2. Shape
١١
Capsule Shape
Traditional, Locked
Prefit
non-inetrlocking
Capsule Shape
١٢
3. Moisture Content
4. Solubility
١٣
Capsule Filling
Capsule Filling
Type of Material for Filling
z Dry solids: Powders, Pellets, Granules, Tablets
z Semisolids:
• Thermosoftening mixtures (during filling are in the molten state and
fluid enough to be pumped and filled. On standing solidification
happens. E.g. PEG 4000, solid fat.
• Thixotropic mixtures: thin with low viscosity upon shearing by mixing
and form hard mass with high viscosity upon standing when
shearing ceases. During filling they are fluid and semisolid during
shelf life.
• Pastes.
• Liquids: Non-aqueous liquids: requires sealing by applying gelatin
solution
l ti att the
th cap-body
b d jjoint
i t tto fform sealing
li gelatin
l ti b
band
d upon
drying. If not sealed leakage at the joint will happen during handling.
Sealing also reduces oxygen permeation into the content, protecting
them from oxidation.
١٤
Filling of Powder Formulations
Bench – Scale filling
| Bench-scale filling:
١٥
Filling of Powder Formulations
Bench – Scale filling
١٦
Filling of Powder Formulations
١٧
Filling of Powder Formulations
Dependent dosing (Auger) Systems:
C
Consists
i t off three
th stations
t ti
Station 1 : For capsule feeding and opening.
Two rings with holes or bores (upper for caps and lower for
bodies) are combined and placed under capsule holding hopper.
the capsules are sucked by vacuum into the bores and vacuum is
also used for separating capsule cap and body in a way capsule
cap can stay in upper holding ring and capsule body can stay in
lower holding ring. During feeding, the ring holders are rotated to
allow for row-by-row capsule filling.
The holding rings are separated, and then the lower (body) holding
ring is positioned on the rotary table. The powder hopper is pulled
over the lower ((body)y) holding
g ring,
g, then auger
g inside p powder
hopper (compulsory feeder, such as rotating screw) is started to
run and fill powder into the capsule body. Upon the lower holding
ring turns one circle, the powder hopper is pushed to its original
position away from the ring. Upon filling, the bodies should be
completely filled for minimal weight variation and thus uniformity of
fill weight is achieved only if the capsules are filled completely.
Accordingly, the semiautomatic machines is classified as dosing
d
dependent
d t system
t meaningi ththe system
t use the
th capsule l b
body
d tto
measure the filled powder. Maximum total fill weight (with minimal
weight variation) can be achieved at the lowest rotational speed of
the turntable and vice versa. More than one rotational cycle can be
applied to ensure complete filling of the capsules.
١٨
Filling of Powder Formulations
Hopper
An Auger capsule filling
machine using the ring
system
Auger
Capsule
body plate
١٩
Filling of Powder Formulations
z The weight
g of ppowder filled into the body y is
dependent on the time the body is underneath the
hopper during the revolution of the plate holder.
Visit http://www.youtube.com/watch?v=r2FYbmwV_iU
٢٠
Filling of Powder Formulations
Independent Dosing system
z Dosators.
z Tamping finger and dosing disc system.
٢١
Independent Dosing system
Dosator systems
٢٢
z The dosator system
i th
is the mostt commonlyl
used capsule filling
system.
٢٣
Filling of Powder Formulations
٢٤
Formulation of Capsule Fillings
Powder Formulations:
٢٥
Powder Formulations:
A. Drug
| Low-dose
Low dose potent drugs are the easiest to formulate for capsule
filling. In this case the drug occupies only a small percentage of
the total formulation (<20%) and so the properties of the mixture
will be governed by the excipients chosen.
٢٦
B. Diluent
¾ For drugs that are readily soluble are best mixed with
insoluble diluents such as starch, microcrystalline cellulose,
or calcium sulfate, because they help the powder mass to
break up without interfering with their solubility in the
medium.
C. Glidants
٢٧
D. Lubricant
E. Disintegrants
٢٨
F. Wetting agents
| Are used when the drug is poorly soluble and hydrophobic. They
reduce interfacial tension between drug particles and the
aqueous dissolution medium, promoting solvent penetration and
wettability.
٢٩