1

(Pharmacuetical Preparation and Packaging of Pharmaceuticals)

3
(Solid Preparation) (Semi-Solids)
(Liquids)
(Solid Preparations)
4

1. (Mixed powders)
2. (effervescent granules)
3.
(lozenges)
4.

(Powders)
(single dose)
(Sachets) (Strip-packaging Machine)

(Screw capped bottles)

freeze-dried powers (lyophilised)
ampoules
(Bulk-pack)
fiber plywood

 2

plastic liners polyethylene, polypropylene polyvinyl
chloride

inert atmosphere adrenaline

(Effervescent Granules)


sachets

(Tablets and Capsules)

(friability)

300 .
10.5 . 50,000
12.5 .
5,000-10,000

2 hard gelatine capsules

(paste)
soft gelatine
capsules

hydrolyse acetic acid salicylic
acid

soft gelatine capsules

non-absorbent 8 %

(Bulk quantities)




1.

2.
3.
4.
5.
6.
7.

(screw caps) (snap-on closures)

 4

Polystylene, Polyethylene Polypropylene

370 C 1-4

(strip)

(Unit Packaging)

Strip Blister (Sachet)

strip Blister


firm Cellulose film
Polyethylene firm Aluminium foil

Aluminium foil
25 um
(pinholes)
 5

0.010 film
sheet film adhesive
laminate film extruude composite film

1. Cellophane regenerated cellulose Plastic film

Thermoplastic coat thermoplastic
seal heat seal Cellophane
Cellophane
Polyethylene film
Cellophane Oxygen greases
flavors Cellophane
Nitrocellulose Polyvinylidene chloride 0.0005
seal
2. Polyester
polyester film
seal Vinylidene Polyethylene
seal
3. Foil foil
99.5% Iron 0.4% Silicon 0.1% Aluminium foil


seal (Laminate)
1
Laminate
 6

1 (laminate)
Peper/PE Analgesic tablets
Cellophane/PE Antacid tablets, Vitamin tablets
Foil/PE Effervescent analgesics
Foil/PVC Ointments, analgesics
Acetate/Pliofilm Ointments, cough syrup
Acetate/Foil/Lacquer Antacid tablets, cold capsules
Acetate/Aclar/PVC Antibiotic tablets, Vitamin tablets
Acetate/Foil/Saran Cough syrup
Acetate/Metallized Mylar/PE Antibiotic capsules, Vitamin tablets
Cellophane/PE/Saran Antacid tablets
Cellophane/PE/Foil/Lacquer Antacid tablets
Cellophane/PE/Foil/PE Analgesic tablet, Ointments
Paper/PE/Foil/PE Vitamin tablets

Leak test
Leak test
Leak
test
Desiccator
10 inches vacuum
Desiccator, Vacuum, Vacuum
gauge Desiccator 20-40
10 inches vacuum 30
1 Desiccator

Leak test 15
8
8 Leak test
vacuum desiccator 15 inches vacuum 1
2
15
2 15


1.

2.
3.
4.

5.


1.

2.

3.
1000
Blister Packaging
Strip packaging
Blister
Transparent Thermoformable Plastic Material
Heat-sealable Lacquered Backing Material
Thermoformable Plastic Material Polyvinyl Chloride
(PVC), PVC/Polyethylene , Polystyrene , Polypropylene PVC
laminate PVC
 8

Polyvinylidene chloride (saran) Polymonochlorotrifluoroethylene (Aclar)

PVC/Aclar Saran-coated PVC
2 3 Thermoformable Blister
Materials
2 Laminations
Material Oxygen Transnission* Water-vapor
transmission*
0.002 PE/0.0075 PVC 0.6 0.092
0.0015 Aclar/0.002 PE/0.0075 PVC 1.0 0.034
0.0015 Aclar/0.0075 PVC 1.1 0.035
0.002 PE/0.0075 PVC 1.3 0.170
0.0075 PVC 1.9 0.330
0.002 PE/0.005 PVC 2.6 0.200
0.005 PVC 2.7 0.520
0.001 Nylon 25.0 19.000
0
* CC/24 hr/100 sq.in at 77 F, 50% RH
** g/24hr/100 sq.in at 950 F, 90% RH

3
Material Water-vapor transmission*
Aclar (fluorohalocarbon)
22A, 1 mil 0.055
22A, 1 mil 0.046
22C, 1 mil 0.045
22C, 2 mil 0.028
33C, mil 0.040
33C, 1 mil 0.025
33C, 2 mil 0.015
Cellophane acetate, 1 mil 80.000
Cellophane
140 K 0.400
195 K 0.450
 9

Material Water-vapor transmission*

195 M 0.650
Polyester, 1 mil 2.000
Polyethylene:
Low-density, 1 mil 1.300
High-density, 1 mil 0.300
Polypropylene 1 mil 0.700
Polyvinyl chloride, 1 mil 4.000
Rubber hydrochloride, 1.2 mil 1.000
Saran (PVDC), 1 mil 0.200
Two-ply waxed glassine paper 0.500
Waxed glassine paper 3.000
Waxed sulfite paper 4.000
* g loss/24hr/100 sq.in/mil at 950 F, 90% RH

Blister

Push-Through Packs Aluminium foil Saran

Blister
paper/foil combination
Blister packaging strip packaging
1.
2.
3.
21 21
Blister packaging Blister
strip
Blister packaging strip packaging
(Semi-solid)


 10

Ointments, Creams, Pasters, Soft extracts, Liquid glucose, Balsams resins

Ointments bases
bases
bases Mineral oils, vegetable oils, soft paraffin, hard paraffin,
wool fat, Beeswax Emulsifying agent Cetomacragol

Creams Emulsions
Semi-solids 2 Oil-in-water Hydrocortisone Creams
Water-in-oil Proflavine Cream powder
aqueous solution
Pastes
Creams powdered solids Oily Greasy bases
Glycerin Pastes Coal Tar Paste, Magnesium Sulfate
Paste Unnas Paste
Semi-solids
semi-solids
(Glass)
compatibility


(amber glass)

contamination
(metal)

50 . Stainless steel Mild
steel stainlees steel
 11

Mild steel
Plastic liners

5 10 15 30
contamination oxidation
British
Pharmacuetical Codex (B.P.C.) Aluminium tubes
phosphate buffer
0.1% anhydrous disodium hydrogen phosphate 0.2% sodium dihydrogen phosphate



Membrane Membrane
cork wads

(Plastics)
Ointments, Creams Pastes
High density polyethylene

Methyl salicylate P.V.C. Polystylene Dimethyl
phthalate phthalate esters polystyrene fixed oils
polystyrene
British Standard (BS.)
Ointments, Creams Pastes

contamination


 12

Oxidation

(LIQUID)

(syrups) glycerin, oils, organic solvent

15 30 60 120

1

Polyethylene

1. (Aqueous oral preparations)
2. (Aqueous non-oral preparations)
3. Emulsions
4. (Injections)
5. (Non-Aqueous Liquids)
 13

(AQUEOUS ORAL PREPARATIONS)

Infusions (Macerating)

Extracts Infusions
Crudedrugs (Percolation)
Alkaloids
Extracts Extract of Quillaia Extract of Senega Extract of
Squill
Stainless steel
Syrups
Syrups

stainless steel Syrups
Stability test
Syrups 60%
Syrups
Syrups Syrups
Syrup Syrups

Elixirs Elixirs Syrups Elixirs

Elixirs Syrups

(AQUEOUS NON-ORAL PREPARATIONS)

Lotions Aqueous solution Zinc Sulphate Lotion

Suspension Calamine Lotion Lotions
Lotions
Lotion
Phenolic substances
Disinfectants Bactericides
Eye Lotions Lotions

 14

Lotion Sodium bicarbonate

alkali Soda glass High density polyethylene

Eye Drops
Eye Lotion


autoclaving Heating

(Neutral glass) Soda glass treated alkali

Nozzle
contamination

Bactericides Eye
Drops
Eye Drops
(Disposable container)

EMULSIONS
Emulsions
Emulsions
(Oil in Water) Emulsions

(INJECTIONS)

(ampoules)
(vials)
 15

Electrolyte solutions polyethylene
polyprpylene polyvinyl chloride
alkali pH solutions
Air-inlet contamination
P.V.C.

Non-Aqueous Liquids
Alcohol Ethyl alcohol organic solvent

45% 80%
percolation maceration

Tincture
of Iodine Iodine
Iodine
Essential oils
polythene Tincture of Chloroform and Morphine
polythene peppermint oil, chloroform ether
polythene

Oils fixed vegetable oils Olive oil, Arachis
(peanut) oil, Caster oil Almond oil
P.V.C.
High density polyethylene polypropylene
Oils Low density
polyethylene
 16

2
(Spoilage Mechanism)

Chemical incompatibility, acidity, alkalinity,
hydrolysis, trace elements, metals, atmospheric conditions, light, heat



(Oxidation)
(Heat)

Volatile liquids


biological nature Vitamins,
Hormones, vaccines, antibiotics antitoxins

Plastic forms
Vaccines 100C
fiberboard

(Moisture)



 17

ammonium sulfate, sodium chloride,

potassium citrate
anhydrous chemicals dried
sodium sulfate, dried sodium carbonate, dried magnesium sulfate

Magnesium Sulfate Paste Mixture of dried magnesium sulfate and
glycerine
magnesium sulfate
Organic chemicals
aspirin hydrolyse salicylic acid acetic acid
digitalis

Penicillin 1000C

High density plyetylene polypropylene

foil/film/paper laminations



silica gel

 18

(Light and Oxidation)

Oxidation Parakdehyde
oxidise acetaldehyde peroxide
B.P.

Oxidise
ferrous salts, mercuric salts organic compound chlorpromazine oxidise
inactive sulphoxy compound
Antibiotics chloramphenical Tetracycline
Hormone Adrenalin Insulin Glocosides digitalis Vitamins
Vitamin A, thiamine, riboflavine, pyridoxine, cyanocobalamine, folic acid, ascorbic acid
calciferol steriods cortisone, prednisone, prednisolone Vaccines
Bacterial Viral
Oxidation inert gas
Nitrogen adrenalin, ascorbic acid ergometrine

oxidation

(Other factors)



 19

contamination
ascorbic acid Thiamine hydrochloride
lacquers
plastics liners
Carbon dioxide insoluble
carbonates lead Calcium Magnesium oxide
magnesium carbonate

3
(Sterilisation)

Sterilisation
Bacteria, Virus Fungus

sterile
Eye drops, Eye ointments, Eye lotions
sterile
sterile

sterile sterile
sterile
sterile sterile seal

sterile
1.

sterile
 20

coagulation protein sterile

sterile 2 Dry Heat Moist Heat

Dry Heat 1400 C
(2840F) steile 1800 C (3560F) 2
2600C (5000F) 45 spores
vegetative forms sterile
1500 C 1 1900 C 90
sterile Dry Heat collapsible tubes
Moist Heat sterile Dry Heat coagulation
Cell protein Dry Heat 20
15 (1210 C) 3 27 (1320C)
sterile

B.P.C. sterile 1
3.1 Exposure time to effect sterilization
Pressure (in excess of Atmospheric)
Temperature 0C Time (min)
Kgf/cm2 Lbf/in2
115-116 0.7 10 30
121-123 1.05 15 15
126-129 1.40 20 10
134-138 2.55 32 3

autoclave
sterile
autoclave Thermal shock


sterile
Polystyrene
 21

autoclave sterile

sterile


autoclave
Polyethylene, polypropylene Plasticised P.V.C.
sterile autoclave
autoclave
autoclave
Indicators Indicator Thermocouple
recorders
Thermoocouple Indicator wax chemical
pellets 1210 C Paper strips

2. sterile
1. Ultra-violet Light Ultra-violet
sterile
aseptic processes Ultra-violet mercury vapor lamps
wave length 2537 Angstrom units

Ultra-violet
2
20
microwatts per cm2 1100
B. subtilis spores S. hemolyticus 275
Ultra-violet lamp 30 watts
85 mw. / cm2 1 S. hemolyticus
65 1 Ultra-violet
2537 A. wave length
 22

3.2 Intersity of Radiation at 2537 A. Necessary to completely Destroy Certain

Microorganisms
Organisms Energy (nw.-sec/cm2)
Bacillus subtilis 11000
B.Subtilis spores 22000
Eberthella typhosa 4100
Escherichia coli 6600
Pseumonas aeruginosa 10500
Sarcin lutea 26400
Stapphylococcus hemolyticus 6600
Streptococcus cerevisial 5500
Saccharomyces cerevisial 13200
Penicillium roqueforti 26400
Aspergillus niger 330000
Rhizopus nigricans 220000

2. Infra-red
Infra-red
sterile
3. Ionizing radiation contents
living cells Ionizing radiation 2
1) High energy radiation Electron acclerators
sterile
2) Gamma radiation Cobolt 60 sterile
Thermoplastics sterile
3) sterile (Chemical Processes of Sterilization)

1) Gas sterilization packaging
materials
autoclave Dry Heat
sterile Ethylene oxide, Propylene oxide, formaldehyde
B-propiolactone Ethylene oxide
 23

Ethylene oxide Boiling point 10.70 C

sterile Ethylene oxide
1. (Concentration)
carbon dioxide, nitrogen chlorofluoromethanes
Ethylene oxide 10-15%
2. (Temperature) Ethylene oxide
Ethylene oxide 600 C
3. (Humidity)
sterile sterile
sterile 30%
4. (Expossure time) 2 24
sterile
sterile sterile
Ethylene oxide
Ethylene oxide
Ethylene oxide
sterile sterile

2) surface Disinfectants Chemical disinfectants
Disinfectants spores

disinfectants
Disinfectants
contaminate
Disinfectants spores vegetative form

Disinfectants

Phenolic compounds
Disinfectants 2% solution
Phenolic germicide 1:1000 concentration quaternary ammonium solutions 1-
2% solution Phenolic germicides
 24

0.2% sodium bicarbonate Phenolic germicides

3.3 sterile
Dry heat Autoclaving Gamma radiation
Material 0 Ethylene oxide
(160 ) (1150 C) (2-5 Mrad)
Glass Satisfactory Satisfactory Discolours Satisfactory
Metal Satisfactory Satisfactory Satisfactory Satisfactory
Paper Embrittled Satisfactory Satisfactory Satisfactory
(Permeability to (permaebility is
steam sufficient sufficient to
to permit the use permit
of paper sterilisation of
wrapping of articles in sealed
articles to be packages)
sterilised)

Carbroard Embrittled Unsuitable Satisfactory Satisfactory

Rubber:
Natural Unsuitable Satisfactory Satisfactory Satisfactory
Nitrile Satisfactory Satisfactory Satisfactory Satisfactory
Butyl Some grades are Satisfactory Unsuitable Satisfactory
softened (liquefied)
Silicone Satisfactory Satisfactory Unsuitable Satisfactory
(liquefied)
Neoprene Satisfactory Satisfactory Satisfactory Satisfactory
(but HCl may be
Thermoplastics: evolved)
Polythene Unsuitable Unsuitable Satisfactory Satisfactory
(low density) (film 150 um
thick
sufficientlyperme
able for articles
to be sterilised in
 25

Material Dry heat Autoclaving Gamma radiation Ethylene oxide

(1600 ) (1150 C) (2-5 Mrad)
Sealed
containers)
Polythene Unsuitable Moulding may Satisfactory Satisfactory
(high density) be distorted due
to stress
release.Film
requires support
of other
autoclavable film
(e.g. nylon)
P.V.C. Unsuitable Unsuitable Satisfactory(HCl Satisfactory
(unplasticised) (distorted) may be released)
P.V.C. Unsuitable Some grades of Satisfactory(HCl Satisfactory
(plasticised) film Satisfactory may be released)
P.V.C./P.V.D.C Unsuitable Some grades of Satisfactory Satisfactory
copolymer film Satisfactory
(Nylon 66
sufficiently
permeable for
articles to be
dterilised in
sealed packages,
but process must
be modified to
avoid bursting
during cooling
phase)
Polystyrene Unsuitable Unsuitable Satisfactory Satisfactory
Polycarbonate Unsuitable Satisfactory Satisfactory Satisfactory
Polypropylene Unsuitable Satisfactory Satisfactory Satisfactory
 26

Material Dry heat Autoclaving Gamma radiation Ethylene oxide

(1600 ) (1150 C) (2-5 Mrad)
(but some
degradation may
occur unless
stabilised)
p.t.f.e. Satisfactory Satisfactory Unsuitable Satisfactory
(fluorine
evolved)
Polymethyl- Satisfactory Satisfactory Satisfactory Satisfactory
pentent
Thermosetting
plastics:
Phenol Some grades Satisfactory Satisfactory Satisfactory
formaldehyde Satisfactory
Urea Unsuitable Satisfactory (but Satisfactory Satisfactory
formaldehyde (degradation and not on sealed
discolouration) containers)

4
(Packaging Materials)

(Glass)

inorganic substances
Silica (SiO2)
Lime (CaO) Calcium carbonate
Soda (Na2O3) Symthetic sodium carbonate
 27

Aluminium oxide (Al2O3) Aluminium hydroxide (Al(OH)3)

alumina Boric acid
Metaic oxides



Dry Heat Autoclaving

(sealing)

Ampoules
Semi-automatic
fully autonatic

(Types of Glass)
"Soda Glass" "White flint
glass" Silica 72% Lme 11% Soda 14%

Amber Glass USP
"Lght Transmission"

 28

4.1Limits for Glass Types I, II and III and PlasticClass I-VI

Maximum Percentage of Light Transmission at any

Nominal size (in ml.) Wavelength Betwween 290 mm and 450 mm
Flame-sealed containers Closure-sealed containers
1 50 25
2 45 20
5 40 15
10 35 13
20 30 12
50 15 10

50 ml 50 ml
Light Transmission USP

Neutral Glass
Alkali


weathering Sodium carbonate
alkali carbon dioxide

(Spicules)
Sodium bicarbonate lotion Soda glass

 29

alkali
alkali
alkali Pyrex Soda 3.5%
Silica 80% Boric acid 13%

Ampoules Vials 100 cc
Jena tubing Silica 66% Soda 8.5%
Alkalinity
Sulphated Glass Soda glass
Sulphating acidic fumes
5000 C alkali
(neutralised) Sulphated bottle autoclave
pH alkali sterile autoclave
Transmission fluids
Sulphated Glass USP NF Type II Treated
Soda-Lime Glass USP NF 4
Type I - Highly resistant, borosilicate glass
Type II - Treated Soda-lime glass
Type III - Soda-Lime glass
NP - General purpose soda-lime glass
2
Powdered Glass Type I, III, NP Water Attack
Type II USP
USP B.P. 3
Type I,II III Type III Non-aqueous
injections Powders
(Plastics)

 30

Polymers
Polyethylene, Polypropylene, Polyvinyl chloride, Polystyrene
Polymethyl methacrylate, Polyethylene terephthalate, Polytrifluoroethylene Polyamides
2
1. Thermoplastics

2. Thermosets


Polyethylene Polythene Thermoplastics
Polymerisation Ethylene 2 Low density polyethylene High density
polyethylene 3
1. Extrusion
2. Injection moulding
3. Blow moulding
Polyethylene Low High density

High density
Polyehtylene Density 0.91-0.96
Density
Density

Polymers Oxidative degradation

Antioxidants Butylated hydroxy toluene Dilauryl
thiodipropionate Antistatics
Antistatics
Polyethylene glycols Fatty amides 0.1-0.2%
Polyethylene

Acids strong oxidising acids Sulphuric acid, Nitric acid
Phosphoric acid Glacial acetic acid
 31

Halogens free halogens Tinctures

Iodine Chlorine solutions

Oils Fixed Mineral Oils Castrol Oil

Oils Essential Oils
aldehydes Ketones
Compound Tincture of Cardamon Peppermint Oil

Solvents Organic solvents

Organic solvent Chloroform Ether
Chloroform preservative Sweetening
agent

Gases Polyethylene
Oxidation Adrenalin solution

Odour Polyethylene
Methyl salicylate Polyethylene

Sorption and Permeation Polyethylene

Bactericides Phenylmercuric nitrate, Methylparaben, Propylparaben,
Benzalkonium chloride, Phenylethyl alcohol Benzyl alcohols
Polyethylene Aromatic alcohols Phenol
preservatives Chlorocresol Phenylmercuric nitrate Benzoic acid
Medium density Benzalkoniumm chloride Chlorhexidine diacetate
preservative
polyethylene
Steroids alkaloids Pilocarpine, Hyoscine, Strophanthin
Ouabain Tincture of Belladonna, Hysocamus
Opium
Leaching
Antioxidants Antistatics monomer catalyst
 32

Light High density polyethylene colourants

Stress crackinf
High density Low density

stress cracking Soft soap B.P., Detergents, Organic

esters, Terpentine and turpentine liniments, Lysol, Acetone, Castor Oil, Chloroform, Ether,
Lineed Oil, Potassium hydroxide conc, Sodium hydroxide conc, Vegetable oil

Polyethylene Molecular weight

Molecular weight Melt flow
index Melt flow index Molecular weight Melt
flow index 0.4
Polypropylene Polymerisation Propylene
CH:CH-CH3 High density polyethylene
3 Extrusion, Blow moulding Injection moulding

Polypropylene High density
polyethylene (0.90)
Thermoplastics Polypropylene
Polyethylene High Density Polyethylene 120-
1300 C Polypropylene 1500 C sterile
autoclave
Electrolyte solutions Intravenous infusion
Polypropylene Polyethylene
Polypropylene Polyethylene
Oils Ointments, Cream Liniments Emulsions
Oxygen, Carbondioxide Low density polyethylene
Polypropylene Strong
nitric acid Sulphuric acid
 33

Sorption Bactericides
Polyethylene Chlorhxidine acetate, Methylparaben, Phenyl
mercuric nitrate Benzalkonium chloride Benzyl
alcohol, Phenoxetol, Phenol Benzoic acid
Leaching Polypropylene Anti-
oxidants stabilisers Oxidation
Polyvinyl Chloride (P.V.C.) Polymerisation Vinyl chloride
CH2-CHCl
1. Unplasticised P.V.C. (U.P.V.C.) Extrusoin
Blow moulding
Thermoforming Blister packs
2. Plasticised P.V.C.
Liners
P.V.C.
Vegetative Oils,
Mineral Oils, Essential Oils Polyehylene
P.V.C. Ketone
Esters Low density
polyethylene
P.V.C.
Polyethylene U.P.V.C. 400 C
80-850 C Plasticised P.V.C. 500 C
750 C P.V.C. degrate sterile
degration sterile
autoclaving P.V.C. stabiliser Plasticiser
P.V.C. Additives
Stabilisera, Anti-oxidants, Lubricants, Fillers Pigments Flexible grades
Plasticisers P.V.C.
additives
Stabilisers degradation
unplasticised P.V.C. organic compounds Plasticised
grades barium cadmium flexible grades plasticisers
 34

phthalate, phosphate sebacate esters high alcohol ( dioctyl

phthalate) fatty acids
unplasticised P.V.C.

25-250 P.V.C.
Methyl salicylate
Collapsible tubes plasticised P.V.C.


pigment
Polyethylene
Polypropylene P.V.C. P.V.C.
Additives

Polystyrene Aromatic compound Polymerisation
Synthetic styrene C6H5CH:CH2 Polystyrene

coloured pigments
Polystyrene Extrusion
Injection moulded Blow moulded
Polystyrene

Solvents
organic solvents Methyl salicylate
Polypropylene

Polyvinylidine Chloride (P.V.D.C.:Saran) Polymerisation

Vinylidine chloride CH2CCl2 Copolymerised vinyl chloride
Saran cap wads
Cellulose Polypropylene strip packaging
P.V.C. Blister packaging
 35

Saran Chemical solvents

Polycarbonate
1600 C sterile
autoclave sterile 1350 C
Biological preparations
vials syringes
Polycarbonate oxidizing reducing
agents, alkalis, amines, ketones, esters, aromatic
hydrocarbons alcohols
NYLON (Polyamide) Synthetic polyamides dibasic
acids diamines dibasic acids diamines
Nylons autoclave
organic Inorganic chemicals

Nylon
Nylon Nylon
THERMOSETS
Urea formaldehyde (u.f. resin) Urea,NH2CONH2
Formaldehyde, HCHO alkaline catalyst monomers
acidic catalyst, lubricant, filler pigments
polymerisation cross
linkage
degradation

solvents decompose
sterile
dry heat
Phenol formaldehyde Thermosetting plastic
Bakelite Phenol, C6H5OH formaldehyde, HCHO alkaline
catalyst
 36

resin

Phenol formaldehyde
Urea formaldehyde Phenolic
solvent strong oxidising acids
strong alkalis Urea formaldehyde
sterile autoclaving asbestos silica fillers sterile
dry heat 150C

5
Permeation, Leaching, Sorption, Chemical reaction
(Modification)
Permeation
Hydrolysis Oxidation



Nyoln hydrophillic
Polyethylene hydrophobic
density
high density polyethylene Low density
polyethylene additives plasticisers colorants

 37

4.1

4.2 Oxygen

Blow moulding
Oxygen
Leaching Additives
Additives
stabiliser Additives

Sorption


Preservativces
 38

Chemical structure, pH , Solvent , system

Chemical Reactinity

Modification
Permeation, Sorption Leaching
polyethylene
solvents oils
polyethylene fluorinates hydrocarbons polyethylene
polyvinyl chloride

4.2
Resistance to
Weight Acids
Clarity Alkalines
Toughness Oils
Water absorption Solvents
Water vapor permeation High humidity
CO2 permeability Sunlight
O2 permeability Heat
Effect on taste Cold
Effect on odor Stress cracing
Effect on color Product effect
 Water Vapor Rate Oxygen Perm.
gm/100 Sq in/24 Cc/100 sq. in. @ Bottle Cost Relative FDA acceptability
Material (density) Inertness
hrs @ 1000 F 950 730F /mil to HDPE for Foods
R.H.

High Density PE Outstanding 0.5 120 1 Yes

(0.955)
Low Density PE Excellent 1.1 450 1.5 Yes
(0.920)
Polystyrene Very poor 10.0 380 1.1 Yes
(1.05)
Rigid PVC Poor 2.7 15 2 Yes (Some
39

(1.35) formulations)
Polypropylene Good to Excellent 0.4 230 1.3 Yes
(0.90)
Nylon 6, 10 Good 2.9 3 3.0 Yes
(1.10)
Polycarbonate Poor 14.0 230 3.5 Yes
(1.20)
Acrylic Fair 11.5 30 2.1 Yes
Multipolymers
(1.10)
Polymonotrifuoroeth Outstanding 0.1 3 40 Yes
ylene (2.10)
 Material Color Toughness/ Outstanding Outstanding
(density) Clarity Impact Adventages Disadvantages
High Density PE Colorless, Translucent Excellent Interness, low cost low Transfer of taste , high
(0.955) WVT, toughness dilute solution
absorption
Low Density PE Colorless, hazy Excellent Squeeze property, Flexibility, relatively
(0.920) inertness, low cost poor barrier to
nonpolars, high WVT
Polystyrene Colorless, clear Poor Clarity, stiffness, cost High WVT,
(1.05) susceptibility to
cracking poor impact
Rigid PVC Colorless, clear Fair Clarity, stiffness, 10-20 ingredients
(1.35) O2barrier, retention of maybe, difficult
nonpolar materials processability, solvent
susceptibility
40

Polypropylene Colorless, clear Good (Poor at 400 F Inertness, low cost, Low temperature
(0.90) and below) ESCR resistance brittleness, tendency to
unzip, high stabilized
content
Nylon 6, 10 Colorless, hazy Excellent Good barrier for Cost, water absorption,
(1.10) nonpolars, tough, good borderline for water-
o2 barrier based materials
Polycarbonate Colorless, clear Outstanding Very tough, clear, good Cost, susceptibility to
(1.20) oxygen barrier solvent cracking, poor
WVT, poor barrier
Acrylic Multipolymers Colorless, clear-hazy Good Clarity, fair oxygen Poor WVT, blusgers,
(1.10) barrier, good for oils poor barrier
Polymonotrifuoro Colorless, clear Excellent Outstanding barrier for Excessive cost, difficult
ethylene (2.10) polars and gases to fabricate
 41

(Metals)
2
Aluminium Tin
Aluminium


sterile

(Rigid container)
Extrusion



aerosols

aerosols

Collapsible tube
99.70%
10 60 . 35-
260 . 1.6 . 558 . Nozzle
3.18 8.38 .

Collapsible tubes Ointments

Creams


Epoxy resin

Conductivity test Power

supply Sodium chloride Electrolyte solution
 42

Foil
Aluminium foils
(Pinholes)
Foil polyethylene seal
foil
99.5% Iron 0.4% silicon 0.1% Iron
foil

Hydrochloride acid Phosphoric

acid Nitric acid
Sulphuric acid 50% 50%
Citric Acetic acids

Hydroxides Potassium, Sodium Magnesium
Calcium hydroxide
Halogens
Bromine, Chlorine, Fluorine Iodine Alcoholic
solutions Iodine (Tincture of Iodine)
chlorides 0.05%

pH 5.5-8.5 Chlorides

99.0-99.7% (99.99%)

Tin and Tinplate

Halogens
Alcoholic solution Iodine

 43

Collapsible tube 99.25%

Ointments creams

Tinplate
15 um




Tinplate
Phenol Phenolic derivatives Salicylic acid Benzoic acid
Tinplate
Tinplate Lacquer

5
(Closures)

seal


Collapsible tubes
(Glass Bottles)

1. (Screw caps)
2. (Stoppers and Plugs)
3. (Snap-on closures)
(Screw caps) 2
(Metal) (Plastics)

Torque tester
 44

Aluminium Aluminium alloy Tinplate

Tinplaste
Tinplaste

Rolled-on
(Capping machine)



Rolled-on
Pilfer-proof (r.o.p.p.)

Thermosets Urea formaldehyde phenol formaldehyde
Phenol formaldehyde
Urea formaldehyde Phenol formaldehyde
Phenol
Thermoplastics
Polystyrene, Polyethylene Polypropylene Polystyrene
Polystyrene

medium density polyethylene

solvent
(Permeability)

Polypropylene
Polyethylene Polypropylene
Urea formaldehyde Phenol
formaldehyde Polyethylene Polypropylene
Urea formaldehyde Phenol formaldehyde

 45

seal
Wad Wads
thermoplastics, pulpboard composition cork (Cork agglomerate) sterile
autoclave wad
Pulpboard
composition cork
28 . Composition cork 2 Gum-bonded
Resin bonded Resin bonded synthetic resin
Gem-bonded composition cork
Wax cap wads pulpboard
composition cork treat
wads
- Blackal oleo-resin
- Cerresin oleo-resin varnish
- Melinex polyethylene teraphthalate
- Polyethylene
- P.V.D.C.-Saran , Steran
- Aluminium foil
- Tinfoil
- Tinfoil-Mexlinex
- Alumimium foil / wax

Blackal Ceresine
P.V.D.C.
Melinex B.P.C. sterilizable facing rubber
wads benzalkonium chloride silicone
rubber
Aluminium foil Tinfoil alcohol volatile solvents
Aluminium foil Tinfoil
aluminium seal Tinfoil Aluminium foil
 46

Tinfoil/Melinex
Tinfoil Melinex

Aluminium foil/wax
foil wax

Wads Urea formaldehyde formadehyde Wads
Polyethylene

(Stoppers and Plugs)

Corks stoppers
stoppers solvents
Reagents
stoppers Polyethylene
stoppers

Polyethylene Plug
Plug-type Dessicant Dessicant

rubber stoppers

Butyl rubber stopper Vials
(Snap-on closures) Polyethylene
Snap-on closure


Snap-on closures Volatile liquids alcohol rubber plugs
Polyethylene plugs
Snap-on closures Pilfer-proof seal
Pilfer-proof
(Plastics containers)

High density
 47

polyethylene

seal


Polystyrene , Polypropylene Unplasticised
P.V.C. Polyethylene Wads

(Injection Closures)
Aqueous solution, Oily solutions, Freeze-dried solids
Powders
1.
2.
3.

4.
5.

6. sterile
7.
British Standard BS 3263

Penetrability
Fragmentation
Self-sealability
Water extractives
Acidity or Alkalinity
Product compatability
Water vapour permeability
2
 48

1. Flanged hollow plugs

seal

2. Flat rubber dises Wads
seal


(Synthetic rubbers)
Butyl rubbers fixed oils
freeze dried penicillins vaccines
Silicone rubbers (Silastomers)

Sorption
Leaching
Bacteriostatics benzyl alcohol, cresol chlorocresol, Chloroxylenol, Phenol, Phenol
mercuric nitrate thiomersal

B.P. autoclave Bactericidal solution

Bactericide Sodium
metabisulphate Bactericidal solution Sodium metabisulphate
0.1% solution 48
Bactericides
1.
2. solution
3.
4.
5. solution
6.
Sulphur
fillers
Leaching
solvents soluble additives
accelerators antioxidants
 49

Sorption Leaching
paraffin wax treat p.t.f.e. epoxy resins

Sorption Leaching
Particulate matter particles
Additives fillers

(Collapsible Tubes)

Urea formaldehyde Phenol
formaldehyde sterile Phenolic
Wad Cork facing foil
Wad Cork
Polyehtylene Wads sterile

British Standard
volatile ingredients seal seal
Menbrane nozzle

Lot No.

(Oily consistency)
sealing band
sealing material 6 .
seal

seal seal
Nozzle
 50

stopper plug

1.
1.1


1.2

1.3
2.

2.1 (nominal size)
(fill point)
(Drawing)
3.
3.1 1 1
3.2 (finish)
3.2.1 2
H
(helix angle)
pitch
tan =
(Tav + E av )
2
 51

1 ( 3.1)
 52

1
ml
3
cm A C
15 21+1.0 30 55.0+0.8 30.0+0.8 28
20 26+1.0 35 57.0+0.8 33.0+0.8 28
30 38+1.5 53 65.0+0.8 38.0+0.8 31.5
60 69+2.0 70 79.4+0.8 44.4+0.8 31.5
100 123+3.0 99 84.0+1.0 52.0+1.0 46
120 143+3.0 121 90.0+0.9 57.0+1.0 46
150 173+3.5 142 100.0+1.0 59.0+1.0 46
200 223+4.0 170 115.0+1.0 62.0+1.2 46
300 332+5.0 255 134.0+1.0 70.0+1.5 53
500 530+6.0 340 149.0+1.1 83.0+1.4 53
750 782+7.5 454 90.0+1.5 90.0+1.5 53
1000 1032+8.4 567 95.3+1.6 95.3+1.6 53

53
 54

3.2.2
0.10

0.2 20
3.2.3 1

3.2.4 T L
(go, no go gauges) 3
4.
4.1


4.2
(flint) (amber)
4.3
- .362
0.01
15
 55

3 ( 3.2.4)

1. 1
T min 1
L min
20 20
2. ()

3. ()
H T F L
4. (under size)
1/12
5.
 56

4.4

. 362
4.5 (light transmission)
10
290 450
.362
4.6
4.6.1 2 .
4.6.2 2 . 200
100
.362
5.
5.1

(1)
(2)

5.2


6.
6.1 .362

 57

15 1000

1.
1.1


1.2 15
1000
1.3
2.

2.1 (nominal size)

3.
3.1 2
3.1.1 1 1
3.1.2 2 2
3.2 (finish) 2
3.2.1 3
H
(helix angle)
pitch
tan =
(Tav + E av )
2
3.2.2
0.10
0.2
20
3.2.3 1

 58

3.2.4 T L
(go, no go guages) 4

1 ( 3.1.1)
 1
( 3.1.1)

.. .



A B C
15 16.0+1.0 19.0+1.0 30 65.0+0.8 20.0 27.0+0.8 22
30 31.5+1.5 36.5+1.5 53 82.5+0.8 30.0 34.0+0.8 22
60 62.0+2.0 72.0+2.0 70 100.0+1.0 36.0 40.0+1.0 24
100 103.0+3.0 115.0+2.5 100 115.0+1.0 33.0 47.0+1.0 28
120 123.0+3.0 135.0+3.0 121 124.0+1.0 33.0 49.0+1.0 28
150 153.0+3.0 168.0+3.5 142 133.0+1.0 38.0 52.5+1.1 28
180 184.0+4.0 202.0+3.5 150 140.0+1.0 43.0 56.0+1.1 31.5
59

240 244.0+4.0 264.0+4.0 190 154.0+1.1 45.0 60.5+1.1 31.5

300 304.5+4.5 324.0+4.5 213 165.0+1.1 45.0 65.0+1.2 31.5
450 456.0+6.0 486.0+5.5 312 180.0+1.1 50.0 77.0+1.2 31.5
500 506.0+6.0 536.0+6.0 340 187.0+1.1 52.0 79.5+1.4 31.5
750 757.5+7.5 789.5+7.3 454 217.0+1.2 56.0 88.5+1.5 31.5
1000 1008.5+8.5 1058.0+8.4 553 235.0+1.3 59.0 97.0+1.5 31.5

1.
2. B B

 60

2 ( 3.2.1)
 2
( 3.1.2)

..


B C D
A

15 18+1.5 30 73.5+0.8 23.0 31.1+0.8 19.8+0.8 18
30 35+1.5 50 92.2+0.8 30.0 37.7+0.8 22.2+0.8 18 5
60 70+3.0 80 114.9+0.9 30.0 48.0+1.0 27.3+1.0 22 ..
(1 )
120 132+3.0 140 134.8+1.0 35.0 58.0+1.0 33.0+1.0 22
150 165+3.0 160 146.0+1.0 35.0 60.0+1.1 36.0+1.1 22 15
180 198+5.0 180 157.0+1.0 41.0 61.5+1.1 37.0+1.1 28 ..
61

240 258+5.0 240 174.5+1.1 41.0 66.0+1.1 40.6+1.1 28 (1 )

300 318+5.0 290 183.0+1.1 41.0 73.0+1.2 42.8+1.2 28

1.
2. B B
62
63
 64

4.
4.1


4.2
 65

(flint) (amber)
4.3
- .
0.01
15
4.4

7.2
4.5 (light transmission)
10
290 450 7.3
4.6
4.6.1 2
4.6.2 2 200
100
7.4
5.
5.1

(1)
(2)


( 2)

5.2


6.

6.1
 66

6.1.1

6.1.2 (defect)

6.1.3 (defective)

6.2
3
6.3
4
6.4
3
4

3 ( 6.2)


280 32 3
281 500 50 5
501 1200 80 7
1201 3200 120 10
3201 10000 200 14
10001 315 21

4 ( 6.3)


1200 3 0
1201 13 1

7.
 67

7.1
0.01


7.2
7.2.1
7.2.2
72+2
1 ( 27
() 5.6
(27 ) ()
0.5 )

15
7.3
7.3.1


7.3.2




(sample holder)

(slit)

(tacky wax)

7.3.3


 68

290 450

(1)
(2) 20

7.4
7.4.1
(1)
100
(monochlorobenzene)
2.5
(2)
(3)
7.4.2
7.4.2.1
40
4
2
7.4.2.2
40 x 40
1

7.4.2.3

30 2
7.4.3
7.4.3.1 1
7.4.3.2 2
 69

2

7.4.3.3 2

1





7.4.4
100
= x 100

.
( 4.3)

.1
(1) (autoclave) 170 *
.4
1210.5
250 .. 6

(vent cock)
* 1.7 (24
)
(2) 5
 70

(3) 50 ..
121
30
(4) 1
(5) 150
(6) (conical flask) 250 ..

121 30
(7) 1
(8) .1

(9) 50 ..
(10) 200 .

(1) 1 . ( .)
(2) 420 ( )
(3) 300 ( )

(11)
(12) 0.5
(13)
1 .
(14) 20 ..
(15)
.2

(1)
(2) (beffer solution) - 5.2
0.1 92.8 .
. 0.2
107.2
(3) 0.1
 71

(C6H8O7.H2O) 21.008
1
(4) 0.2
(Na2HPO4.2H2O) 35.60
1
(5) 0.01
(6)
25 100

(7) -
()
0.1 20

.3
.3.1 1.5 100
2 3
10 30
3 4

2
5

.3.2 35

.3.3


.4
.4.1 11 250
3 30
6

 72

140 20


.4.2 10.00
250 50
50

.4.3 50

4 1 ..

10
1 121
1210.5 30
0.5 100

.4.4
5
0.01
(End point) 50
5


250
25
25
.5
.5
0.1

1.5
 73

.1 ( .1(8))

2000 4000

1.
1.1


1.2 2000
4000
2.

2.1 (nomonal size)


3.
3.1 (stippling)
1
 74

3.2 (finish)
3.2.1 2
(helix angle)
pitch
tan =
T + E av
( av )
2
3.2.2
0.10

0.2 20
3.2.3

3.2.4 T
3
4.
4.1

4.2
(flint) (amber)
4.3
- .362
. 0.1
15
4.4

. 362 7.2
4.5
10
290 450 .362
7.2
4.6
4.6.1 2
 75

4.6.2 2 200
100
. 362 7.4
5.
5.1

(1)
(2)

5.2


6.
6.1 . 362
76
77
78
79