Md.

Alamgir Kabir
Sr. Executive, Production

Pharmaceutics

Ten Commandments of cGMP –

1. Should have written procedure
2. Should follow procedure
3. Should documented (Record) the work
4. Should validate work
5. Should design proper facilities & equipment
6. Should maintain facilities & equipments
7. Should be clean
8. Should be competent enough as result of education training & experience
9. Should control for quality
10. Should audit for compliance

Tablet – Tablet is solid dosage forms containing medicinal substances with or without
suitable diluents.
Classification of tablets –
1. Oral tablets for ingestion
− Compressed tablets

− Multiple compressed tablets

Layered tablets
Compression coated tablets
− Repeat action tablets

− Delayed action tablets and enteric coated tablets

− Sugar and chocolate coated tablets

− Film coated tablets

− Chewable tablets
2. Tablets used in the oral cavity
− Buccal tablets

− Sublingual tablets

− Troches and lozenges

− Dental cones
3. Tablets administered by other routes
− Implantation tablets

− Vaginal tablets
4. Tablets used to prepare solution

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 Md. Alamgir Kabir
Sr. Executive, Production

− Effervescent tablets

− Dispensing tablets (DT)

− Hypodermic tablets (HT)

− Tablets triturates (TT)

Multiple compressed tablets – Multiple compressed tablets are prepared by subjecting

the fill materials to more than a single compression. The result may be multiple layered
tablets or a tablet within a tablet.
Route – Oral cavity, sublingual, Buccal, dental cones
Effervescent tablets – Oral solid dosage form that is added to water before ingesting.
The tablets contain sodium bicarbonate and an organic acids (citric acid / tartaric acid),
evolved Carbon-dioxide gas.
Dispersible tablet – Uncoated tablet that produce a uniform dispersion, which not
evolved any gas
About Tablet Manufacturing –
- Tablets Hardness should be generally 4 kg
- Weight may be variation – ±5%
- Disintegration – The specified time generally falls between 15 to 20 minutes.
- Compressed tablet – In addition to the medicinal agent(s) compressed tablet
contain a number of pharmaceutical excipients including filler or diluents.
Binders, disintegration, ant adherents, lubricants, glidants, coloring and
flavoring agents
- Double impression – This involves only punches that have a monogram or
other engraving on them. Imprinting is mainly dome by lower punch. In some
machines the lower punch is froe to drop and travel uncontrolled in a short
distance
@ During this froe movement, the punch rotates. At this point the punch may make a
new, although lighter impression on the bottom of the tablet, resulting in double imprint.

Tablet Machine Selection

o D Type: Tablets of 25mm die
o B Type: Tablets of 16-21mm die
o BB Type: Tablets of 6-11mm die
o B Type: Tablets of below 40 Kpa Compressions
o BB Type: Tablets of 25 Kpa Compressions

Common parameter of tablets before marketing:

o Physical appearance
o Hardness
o Friability
o Dissolution
o Thickness or Dia (Round shaped tablets)
o Weight
o Disintegration Time (DT)

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 Md. Alamgir Kabir
Sr. Executive, Production

Stability Study:

Temperature Relative Humidity Time

25º ± 5º 45 ± 5% 12 Month
45º ± 5º 60 ± 5% 6 Month
45º ± 5º 75 ± 5% 3 Month

Compressed medicinal tablets may consists of two substance

● Medicaments (Active ingredient)
● Excipients.
Active Pharmaceutical Ingredient (API)
Ideal properties of API:
a) High purity
b) High stability
c) Good compatibility with excipients
d) Optimum bulk powder properties
e) Spherical shape
f) Good flow ability
g) Optimum moisture content
h) Good compressibility
i) Good organoleptic properties
j) Miscellaneous points
k) Absence of static change on surface
l) Optimum and uniform particle size particle distribution.

Excipients

Excipients are inert substance used to give a preparation a suitable form or consistency.
Or
More of less inert any substance added to a drug to give suitable form to the drug.

SI Excipients Definition Examples

No.
1 Diluents/ Diluents are added to tablet formulations to Lactose,
Filler increase the bulk of individual tablet to a Mannitol,
practical, convenient and workable size. Sorbitlol,
Starch
CaCO3
2 Binder Binders are adhesive materials used to hold Solution binders-e.g:
powders together as granules Gelatin solution
(10-20%)
Methyl cellulose 4% in
alcohol.
Ethyl cellulose 5% in
alcohol.
Polyethylene glycol.
Dry binder–e.g

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 Md. Alamgir Kabir
Sr. Executive, Production

Cellulose
Methyl cellulose
Polyethylene Glycol.
3 Disintegrators Disintegrators are substance which is added Dried corn
to tablet formulations, when needed to induce Starch
the tablet to disintegrate or dispersed or Sodium CMC
dissolved after administration. Potato starch
4 Lubricants Lubricants are added to tablet formulation to Magnesium stearate
reduce friction during tablets compression. Stearic acid
Calcium stearate
Talc.
5 Glidants Excipient that added to tablet formulations to MagnesiumStearate
promote the flow of granulation by reducing Calcium stearate
friction between particles. Talc

6 Coloring It is an agent that use for increasing physical

agents appearance & compatibility & the
pharmaceutical dosage form.

7 Flavoring Pharmaceutical necessity added to oral Banana flavor,

agents dosage form to musk the test unpleasant Strawberry flavor,
flavor of the drug. Mango flavor.

8 Preservative Preservative is used in liquids or semisolids Benzyl alcohol Phenol

which prevent microbial growth Methyl paraben, Propyl
paraben
Boric acid.

9 Emulsifying To reduce internal phase into small globules / Acacia

agent Stabilizer of the droplet form of the internal Cetyl Alcohol
phase of an emulsion Egg Yolks
Gelatin
Na alginate
10 Anti-oxidant It helps to prevent oxidation Reducing agents-e.g:
Sodium bi sulphate
blocking agents-e.g:
Tocopherol.
Synergist-e.g:
Ascorbic acid
Tartaric acid
Citric acid.

11 Preservative The viscosity increasing agent used to reduce Agar

the rate of sedimentation of particles Tragacanth
dispersed throughout a vehicle in which they Methyl Cellulose
are not soluble. Polyethylene glycol
12

1. Diluents / Filler– Diluents are added to tablet formulations to increase the bulk of
individual tablet to a practical, convenient and workable size

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 Md. Alamgir Kabir
Sr. Executive, Production

For example – Lactose, sucrose, glucose, mannitol, sorbitlol, starch, kaolin,

Di-calcium phosphate, calcium carbonate, calcium sulphate.
@Equal part of Lactose and Di-calcium phosphate granulated with starch paste are
frequently used as granular diluents.

2. Binder – Binders are adhesive materials used to hold powders together as granules &
to assist in ultimately holding the compressed tablet together.
Binder is of two types-
- Solution binder
- Dry binder.
Solution binders –
- Starch paste (10-17%)
- Gelatin solution (10-20%)
- Sucrose syrup (50-85%)
- Glucose solution (50% alcohol, 25% glucose and 25% water)
- Methyl cellulose 4% in alcohol.
- Ethyl cellulose 5% in alcohol.
- Starch- acacia paste( starch 5%, acacia 2% in water)
- Sodium CMC.
- PVP in aqueous, alcoholic and hydro alcoholic soln
- Polyethylene glycol.
Dry binder –
- Cellulose
- Methyl cellulose
- PVP
- Polyethylene Glycol.

3. Disintegrators – Disintegrators are substance which is added to tablet formulations,

when needed to induce the tablet to disintegrate after administration.
For example- Dried corn / Potato starch / Starch / Cellulose / Sodium starch
glycolate / Cross linked polyvinyl pyrrolidone / Sodium CMC
@ Dried corn or potato starch and cellulose derivatives are the most popular
disintegrating agent.

4. Lubricants (0.5-3% of tablet weight)– Lubricants are added to tablet granulation

when needed, to-
Lubricants may function as –
- Improves the flow properties of granules as well as to reduce the internal friction
- Eliminate adhesion to the surface of punch and die
- To reduce the wall friction and this facilitate the ejection of finished tablet
- Reduce excessive punch and die wear
For example – Magnesium stearate / Stearic acid / Polyethylene glycol / Sodium
lauryl sulphate / Sodium stearyl fumarate / Liquid paraffin

5. Glidants – Excipient that added to tablet formulations to promote the flow of

granulation by reducing friction between particles (use to improve flow property)
For example – Silica / Magnesium / Stearate / Calcium stearate / Starch / Talc

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 Md. Alamgir Kabir
Sr. Executive, Production

6. Coloring agents – It is an agent that use for increasing physical appearance &
compatibility & the pharmaceutical dosage form.
Color from plant – Chlorophyll (Green) / -carotene (Yellow / Orange)
Color is normally added by –
- Dissolving the dye in the binding solution
- Spraying the granules with a special solution of the dye
- Distributing the dye with the dry mix and then employing wet granulation.

7. Flavoring agents – Pharmaceutical necessity added to oral dosage form to musk the
test unpleasant flavor of the drug.
For example –Banana flavor, Strawberry flavor, mango flavor etc.

For liquid Dosage form –

8. Preservative – which prevent microbial growth?
For example – Benzyl alcohol / Phenol / Benzyl conium chloride / Methyl paraben,
Propyl paraben / Butyl paraben / Boric acid / Sodium salicylate / Thimersal

9. Emulsifying agent / Surface active agents (reduce surface tension) – To reduce

internal phase into small globules / Stabilizer of the droplet form of the internal phase
of an emulsion. Emulsifiers are also used as a wetting agents & Surfactant.
@Surface tension – Interfacial tension at an air liquid interface. Surface tension causes
fluids to assume spherical shape.
For example – Egg yolk, Agar, honey, gelatin, Na Alginate
Polysorbate (80, 60, 20) / Potassium oleate / Sodium dodecyl (lauryl) suphate /
Povidone / Propylene glycol / Theophylene / Propylene glycol / Ethyl alcohol /
Glycerin

10. Anti-oxidant – It helps to prevent oxidation

For example –
Anti-oxidant (reducing agents) – Sodium bi sulphate / Butylated anisole / Thiourea /
Anti-oxidant (blocking agents) – Tocopherol / Ascorbic acid esters
Synergist –Ascorbic acid (vitamin – C) / Phosphoric acid / Tartaric acid / Citric acid

11. Suspending agents – Agents used in pharmaceutical suspensions to impart viscosity

For example – Gelatin / Methyl cellulose / Sobitol solution / Polyethylene glycol 4000

Manufacturing problems of tablet-

Poor Adhesion – Insufficient binder can make this type problem
Soft Tablets – Insufficient binder & insufficient compression pressure can make this
type problem
Capping – Capping is a term used to describe the partial or complete separation of the
top or bottom crowns of a tablet from the main body of the tablet. It is due to increase
inter particle space contain air.
To decrease the rotation time of tablet machine or to adjusting the primary compression
pressure
Chipping – Divided into two same part or divided from the middle point of the tablets.
Lamination – Lamination is the separation of a tablet into two or more distinct layers.

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 Md. Alamgir Kabir
Sr. Executive, Production

@ These problems occur due to insufficient binder, improper granulation, layering of

granules. Pressure maladjustment, Entrapment of are into the whole of the tablet, war
punch, lack of enough fine powders.
Picking – Picking is a term used to describe the surface material from a tablet that is
sticking to and being removed form the tablets surface by a punch.
@Picking happens when a punch tip has engraving or embossing. Also happened due to
insufficient lubricant, scratched upper punch & improper drying of granules
Sticking – Sticking refers to tablet material adhering to the die wall. When Sticking
occurs additional force is required to overcome the friction between the tablets and die
wall during ejection.
Mottling – Mottling is an unequal distribution of color of a tablets.

Granulation – It is a process if making particulate mass from fine powdered of drug or

excipients.
Purpose of granulation –
− It helps to prevent powder segregation.

− To improve the flow properties of the mixtures

− To improve the compaction properties of the mixtures

Granules - Primary powder particles are made to adhere to from larger, multi particle
entities is so called granules. Size range for tablet or capsule is 0.2mm-0.4mm.

There is two types of granulation process are available

1. Dry manufacturing method
a. Dry method of direct compression
Process – Raw material weighing Screening Mixing (some time)

Packaging Coating Compression

b. Dry granulation
Process – Raw material weighing Screening Mixing Compressing
(Slugging)

Milling

Sieving

Packaging Coating Compression Final Mixing

2. Wet granulation – Use Planetary mixer for wet massing. High speed mixture /
Granulator.
Process – Raw material weighing Screening Mixing Wet mass

Milling

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 Md. Alamgir Kabir
Sr. Executive, Production

Drying

Milling

Packaging Coating Compression Final Mixing

Name of the machine of different steps of solid / liquid dosage forms

Mesh size – mesh size 20 is called the screen contain 20 pore per square inches (PSI)
Capsule – Capsule is a solid dosage form in which the drug is enclosed in either a hard
or soft soluble gelatin shell.
Capsule size – 8 type of size are available
000(Largest), 00, 0, 1, 2, 3, 4, 5(Smallest)
For 500mg – 00 sizes is needed
For 250 – 1 or 0 size is needed
Shape of soft gelatin capsule – Oval shape / Oblong / Round / tube / suppository –
special shape
Syrup – It is a solution of sucrose in water more than 66.7% intended for oral
administration, often containing flavoring agents with active ingredients

Suspension – Two phase system 1. Solid 2. Liquid Solid phase will not dissolved but
uniformly distribute.
Suspending agent – To decrease sedimentation rate and dispersion
Example – Acacia, Methyl cellulose, free gum, CMC, Gelatin
Suspension type –
● Flocculated – when the sedimentation rate is faster.
● Deflocculated – when the sedimentation rate is slower.
Emulsion – Two phase system in which one liquid is dispersed in the form of small
droplets through another liquid.

Solution – one phase system use in aqueous base Or

A homogeneous mixture of one or more substance dispersed in a sufficient quantity of
dissolving medium

Elixir – One Phase system use hydro alcoholic base

Liniments –
Tinctures –
Enema

Documentation –
− Define information system of the organization

− Future reference

− Business process flow

− Confirms performance

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 Md. Alamgir Kabir
Sr. Executive, Production

− Monitor and control all the activities

SOP – Standard operating procedure
SOP contents are – Name of the company / Title / Identity number / Revision number /
Objective / Prepared by / Approved by / Effective date / Definition / Activity / Action /
Responsibility / Reference / Distribution list
@ SOP’s will be precise and specific and will start with action verb. Ex –Clean the
room with 70% savlon solution
Another 4 component come with the SOP’s –
1. Forms – Rejection note / Conformation notes
2. Check list
3. Log sheet – Mainly use in industry (use in machine repair time )
4. Process control chart – Use in industry IPC
BPR / BMR – Batch Manufacturing Record
Additional component – Safety and precautions should be clearly mentioned / Total yield
(loss NMT 2-3%)
IPC Checks list for solid dosage form –
a. Dispensing –
− Calibration of balance

− Cleaning of balance

− Proper checking of weight

− Accuracy of weight

− Perform the recoding of weight

b. Granulation –
− Mixing time and speed, Temperature (Thermometer)

− Properly milling, Particle size reduction, time

− Drying temperature (inlet & outlet), Time & speed, Pressure & vacuum,
Moisture content of in-process material / products
c. Blending – Homogeneity of the content
d. Compression –
− Machine speed

− Compression pressure

− Hardness of tablets (Hardness tester)

− Appearance of tablets

− Thickness of tablets

− Friability of tablets (Friabilator)

− Weight variation (Balance)

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 Md. Alamgir Kabir
Sr. Executive, Production

− Dissolution time

− Disintegration time

− Moisture content of tablet (Hygrometer)

e. Coating –
− Temperature (inlet & outlet)

− Speed (Revolution) and time

− Uniformity of color (Mottling test)

− Appearance

− Viscosity of coating solution

In a pharmaceutical company there is two parts
1. Hard part – Building / Room / Machine Or Equipment
2. Soft Part – cGMP / Compliance / Attitude / cGMP environment / Training etc.
Calibration – When measuring equipment comply with standard
Traceability – Which Standard is use to comply the measuring equipment. Traceable to
certain organization
DIOP – Design qualification / Installation qualification / Operational qualification /
Performance qualification

Normal solution – Equivalent weight in 1000 ml (In total)

Gram equivalent weight + water = 1000ml. for example: H SO = 98 (molecular
weight)
49 ml of H SO + water = 1000 ml
Molar solution – Gram molecular weight in 1000 ml (In total)
Gram molecular weight + water = 1000ml. for example: H SO = 98 (molecular
weight)
98 ml of H SO + water = 1000 ml
Molal solution – Gram molecular weight dissolve in 1000 ml
Gram molecular weight + 1000mlwater = Molal solution. for example: H SO = 98
(molecular weight)
98 ml of H SO + 1000 ml water = 1098 ml

Temperature chart –
Room temperature – 15-25°C
Cool / Cold temperature – 8-15°C
Freeze temperature – 2-8°C
Deep freeze temperature – Not less then (-15°C)
Ambient temperature or pertinent temperature – In present temperature / Human body
temperature such as 37°C

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 Md. Alamgir Kabir
Sr. Executive, Production

Sterile preparation –

Process 1– Raw material weighing Solvent / Water collection Dissolve

Sealing Filling Sterilization Filter

Process 2– Raw material weighing Solvent / Water collection Filter &

Sterilization

Sealing Filling
Clean Room:
Category
American European / British International Standard Organization
(ISO)
Class A Class 100 Class 3.5
Class B Class 1,000 Class 4.5
Class C Class 10,000 Class 5.5
Class D Class 100,00 Class 6.5

Class A / Class 100 – Means 100 particles of 0.5 micron (µ) are present per cubic feet.
Class 3.5 – Means 3500 particles of 0.5 micron (µ) are present per cubic meter.
Particle Control:
Zone Clean Room Area
Zone A Class 100 Sterile Area
Zone B Class 10,000 Open Handling (Powder
Mixing Room)
Zone C Class 100,00 Close Handling (Ware
house & Packaging room)

Job Responsibilities of a Production Executive:

Preparation of daily routine job for shop Floor Worker
Follow SOP to ensure production activities according to GMP.
Monitor activities of operators and workers.
Departmental manpower distribution.
Ensure cleanliness of equipment and working spaces as well as workers uniform.
Follow Batch Manufacturing Record (BMR) to ensure right job at right time with right condition
with correct machine and man.
Ensure completion of current documentation.
Ensure physical healthy workers and their hygiene.
Monitoring of production in terms of quality first and then quantities.
Follow Batch Manufacturing Record (BMR) to ensure correct Packaging Material for correct
product
Follow up workers discipline.
Training of operators and workers.
Assessment of workers performance.
Documentation of departmental total job

Contents of SOP

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 Md. Alamgir Kabir
Sr. Executive, Production

o Name of the company or honor

o Title of the SOP
o Scope
o Purpose
o Who develop the SOP
o SOP No.
o Distribution List
o Relevant SOP
o Procedure
o Reference

Pharmaceutical Common using terms –

AHU- Air Handling Unit
API- Active Pharmaceutical Ingredient
ASHRAE- American Society of Heating, Refrigeration and Air Conditioning Engineers
BAS- Building Automation System
BMR- Batch Manufacturing Records
BPR- Batch Packaging Records
BMS- Building Management System
BET – Bacterial Endotoxins test
BOD – Biological O Demand
COD – Chemically Oxygen Demand
DQ- Design Qualification
DOE- Design Of Excipient
GEP- Good Engineering Practice
GMP- Good Manufacturing Practice
HVAC – Heating, Ventilating & Air-conditioning
HEPA – Hyper Efficiency Particulate Air
IQ- Installation Qualification
IR – Instant release / Infra Red
ISPE- International Society for Pharmaceutical Engineering
LAL – Limulus amebocyte lysate – the test used to detect minute quantities of bacterial
endotoxins or other pyrogens (Circulating amebocyte from the Horse shoe crab)
MAL- Material Airlock
MHRA- Medicine and Health care product Regulatory Agency. (UK- MHRA Guideline)
MCC- Medicine Control Committee (South Africa)
MSDA- Material Safety Data Sheet
OQ- Operational Qualification
OSD- Oral Solid Dosage
PAL- Personal Airlock
SCADA- System Control and Data Acquisition
TOD – Total Dissolved Solid
TGA- Therapeutic Good Administration (Australia)
UDAF- Unidirectional Airflow
URS- Users Requirement Specification
ULPA- Ultra-Low Penetration Air
WFI – Water for injection

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 Md. Alamgir Kabir
Sr. Executive, Production

Lake – Calcium or aluminum salt of a certified dye extended on a substance of alumina.

Lakes are insoluble in water & organic solvent.
Hygrometer – Relative humidity
Hydrometer – Density of liquid
Monometer –
Glass – Container material composed principally of silicon dioxide. The two general
types of glass are soda-lime glass and Borosilicate glass
Glass specification –
Water attack test – USP test for Type II glass
Titration –
Coating materials –

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