Beruflich Dokumente
Kultur Dokumente
Packaging material
PIC/S GMP
Any material employed in the packaging of a
medicinal products, excluding any outer
packaging used for transportation or shipment.
Packaging materials are referred to as primary
or secondary according to whether or not they
are intended to be in direct contact with the
product.
. .
1
Packaging component
US FDA Container Closure Systems for Packaging Human Drugs and Biologics
. .
2
US FDA Container Closure Systems for Packaging Human Drugs and Biologics
. .
3
Containers
Containers
Well-closed containers
Tightly closed containers
Hermetically closed containers
Light-resistant container
. .
4
Containers (EP)
Single-dose container
Multidose container
Well-closed container
Airtight container
Sealed container
Tamper-proof container
Child-proof container
Containers ( USP31)
Tamper-Evident Packaging
Light-Resistant Container
Well-Closed Container
Tight Container
Hermetic Container
Single-Unit Container
Single-Dose Container
Unit-Dose Containers
Unit-of-Use Containers
Multiple-Unit Containers
Multiple-dose Containers
. .
5
Packaging concerns
Depend on
Dosage form
Route of administration
. .
6
Medium
Low
High
Low
General consideration of
container closure system
1. Suitability for Intended Use
a)
b)
c)
d)
Protection
Compatibility
Safety
Performance
Physical Characteristic
Chemical Composition
. .
7
General consideration of
container closure system
Attributes
Protection
Compatibility
Safety
Performance
Proposed Methods
No leached harmful or
undesirable amounts of
substances to expose patients
treated with drug
. .
8
Physical Characteristics
b)
Dimensional criteria
Physical parameters critical to the consistent
manufacture of the packaging component
Performance characteristics
Chemical Composition
PACKAGING MATERIALS
Glass
Plastics
Metal
. .
9
PACKAGING MATERIALS
. .
10
. .
11
GLASS
Composition
Silica (SiO2)
Calcium oxide (CaO)
Sodium oxide (Na2O)
Alumina (Al2O3)
Other oxide
59-75 %
5-12 %
12-17 %
0.5-3.0 %
. .
12
Test to be performed
Test A
(surface test)
Test A and B or
Test A and C
. .
13
Type III
Up to 1
2.0
20.0
Above 1 and up to 2
1.8
17.6
Above 2 and up to 5
1.3
13.2
Above 5 and up to 10
1.0
10.2
Above 10 and up to 20
0.80
8.1
Above 20 and up to 50
0.60
6.1
0.50
4.8
0.40
3.8
0.30
2.8
Above 500
0.20
2.2
. .
14
ml of 0.02 M HCl
Type I
. .
15
Glass
Coloured Glass
. .
16
Light Transmission
EP
3.2 Container
USP
. .
17
Limits
Filling volume
(ml)
Up to 1
Above 1 and up to 2
Above 2 and up to 5
Above 5 and up to 10
Above 10 and up to 20
Above 20
Container with
closure
50
45
40
35
30
25
25
20
15
13
12
10
. .
18
PLASTICS
. .
19
PLASTICS
1. Thermosets (Thermosetting plastics)
Consist of those plastics that, when subjected to
heat, normally will become infusible or insoluble,
and as such cannot be remelted.
2. Thermoplastics
Consist of those plastics that normally are rigid
at operating temperatures but can be remelted
and reprocessed
POLYMER
Homopolymer :
Copolymer :
. .
20
Plastics
Factors responsible for plastics properties
Chemical structure
Molecular weight
Crystallinity and orientation
Cross-linking
Addition of other agents
Plastics
Chemical Structure
. .
21
Plastics
Molecular weight
Ease of moulding
Impact strength (decreases)
Stress cracking resistance (decreaes)
Plastics
. .
22
Plastics
Orientation
Plastics
Cross-linking
Joints between chains which occur in three
dimensions.
Reflected in physical properties, increasing,
for example, polymer rigidity.
Thermoset are cross-link.
. .
23
Plastics
Antioxidants
Stablizers
Plasticizers
UV absorbers
Antistatics
Dyes or pigments
Lubricants
Etc.
Plastics
Important problems
1. Sorption
2. Desorption (Leaching)
3. Permeation
4. Photodegradation
5. Polymer Modification
. .
24
Thermosets
Phenol Formaldehyde
Urea Formaldehyde
Melamine Formaldehyde
Thermosets
. .
25
Thermosets
Melamine Formaldehyde
Phenol Formaldehyde
Thermosets
Urea Formaldehyde
. .
26
Thermoplastics
Polyethylene
Polypropylene
Polyethylene Terephthalate (PET)
Polyvinyl chloride
Polyvinylidene chloride
Polystyrene
Polycarbonate
Polyethylene (PE)
. .
27
. .
28
HDPE bottles
HDPE bottle which provide
protection from light by using
Titanium dioxide as an
opacifying agent
Polypropylene (PP)
. .
29
Vinyl Plastics
. .
30
Unplasticised PVC
Plasticised PVC
. .
31
UPVC Film
Suppositories package
. .
32
. .
33
Polystyrene (PS)
. .
34
Polycarbonates
Ionomer (Surlyn)
. .
35
Polymonochlorotrifluoroethylene (PCTFE)
Aclar film
Polyurethane Foams
. .
36
PETE
PP
HDPE
PS
PVC
Others
LDPE
Density
O2
CO2
Water
vapor
Clarity
Drop
impact
Chemica
l resist.
LDPE
0.92
300
2700
1.3
F/G
F/G
HDPE
0.98
185
580
0.3
F/G
F/G
PVC
1.32
17
27
3.0
F/G
PS
1.05
330
1160
8.5
F/G
PC
1.20
234
925
10
PP
0.91
135
390
0.3
F/G
OPP
0.91
68
195
0.3
G/E
F/G
OPET
1.36
4.4
31
1.85
PETE
1.33
12
77
F/G
PETG
1.27
24
105
4.5
E/G
. .
37
Density : G/CC
O2 : CC/100 SQ IN. 24 HR (lower = better)
CO2 : CC/100 SQ IN. 24 HR (lower = better)
RATING : P = Poor, F = Fair, G = Good, E = Excellent
Sterilization
Polypropylene
High density polyehthylene
Polycarbonate
PVC for certain application
All thermosets
. .
38
Sterilization
Sterilization
Irradiation
. .
39
Aluminium
Tin
Tinplate
Aluminium
Density of 2.7
Odourless, tasteles, non-toxic and sterilizable
Corrosion
Galvanic corrosion
Electrolytes
Halogen : chloride
. .
40
Tinplate
. .
41
BLISTER PACKAGE
2 basic packaging components
A. Forming film
Thermoformed
Cold formed
B. Lidding Material
Push-through
Peelable
. .
42
Machineability
production rate
Depth of the blister
Wall thickness and uniformity of the thickness
Sealing properties
Unplasticized PVC
PVdC-coated PVC
Aclar / PVC
. .
43
PP
30 PP / 190 COC / 30 PP
30 PP / 300 COC / 30 PP
. .
44
. .
45
Blister
% increase from
blister formation
PVC
3500
6500
86
PVC / PVdC
500
1000
100
PVC / Aclar
200
250
25
. .
46
Strip Packaging
Technical requirements
Cost of base materials
Cost of lamination processes
Amount of laminate required (quantity)
Yield from which the cost per area of laminate is
derived
. .
47
Basic polymer
Vulcanizing agent
Accelerators
Filler
Pigments
. .
48
Drug
selection
Degradation
pathway
Preformulation
Drug
excipient
interaction
Drug
stability
Heat
Packaging
Formulation
Dosage
form
design
Dosage
form
selection
Cool
Amber
Heat
Tight
Sealed N2
Long term
stability
Production
. .
49
Stability testing
Stability Studies
. .
50
Quantity received
Quality required
Nature of material (:- primary packaging
materials and/or printed packaging materials)
Production methods
Knowledge of Quality Assurance system of the
packaging materials manufacturer based on
audits.
PIC/GMP ANNEX 8
Machine performance
New suppliers
Sterile / clean components
Reel fed laminates
. .
51
. .
52