Name : Divy Prajapati

STD : M.Sc Sem IV

Roll No. : 22

College Name : Shree P H G Muni. Arts &

Science College

Topic : Industrial Pharmaceutical

Technology
Nucleus Formulation Pvt. Ltd.

Department
• Raw Material Store
• Production Department
• QC Department
• Packing Department
 Raw
Material Dispensing

Production
Department

Compression
Grannulation
Coating

QC Department
fication of manufacturing methods
wet granulation: suitable for drugs that are stable to moisture and
granulation heat
dry granulation: suitable for drugs that are sensitive to moisture and
heat
powder compression : suitable for drugs that are sensitive to moisture
and heat, fill material possessing, good flowability and compressibility
direct
compression
crystal compression：suitable for drugs with proper crystal form
and good flowability
 • Grannulation
• All Raw Material After Dispensing first step is
Grannulation
• Instruments…1) Mass Mixture
• 2) RMG (Rapid Mix Grannulator)
• 3) FBD (Flued Bed Dryer)
• 4) Miller
• 5) Shifter
• Tablets
• Capsules
• Sugar-coated tablets (dragee)
• Powders
• Granules
 Тablets
• A tablet is a solid dosage form that is
prepared by compressing or molding
of the drug into various sizes and
shapes.
• Dissolution is the rate-limiting step in
the delivery of drug from a tablet to
the systemic circulation.
• Production aspect
• Large scale production at
lowest cost
• Easiest and cheapest to
package and ship
• High stability
• User aspect (doctor, pharmacist,
patient)
• Easy to handling
• Lightest and most compact
• Greatest dose precision &
least content variability
 Tablets for oral administration
• Film coated tablets
• Enteric coated tablets
• Uncoated Tablet
• Medicinal agent
• Diluents or filler
• Binders or adhesives
• Disintergrants
• Lubricants
• Miscellaneous adjuncts
• Colorants and flavorants
Diluents increase the volume to a formulation to
prepare tablets of the desired size. Widely used
fillers are lactose, dextrin, microcrystalline cellu-lose
starch, pregelatinized starch, powdered sucrose, and
calcium phosphate.
• Binders promote the adhesion of particles of the
formulation. Such adhesion enables preparation of
granules and maintains the integrity of the final tablet.
Commonly used binding agents include: water, ethanol,
starch,P V pk, IPA,MDC…
• The breakup of the tablets to smaller particles is important for
dissolution of the drug and subsequent bioavailability. Disintegrators
promote such breakup. To rupture or breakup of tablets,
disintegrating agents must swell or expand on exposure to aqueous
solution. Thus, the most effective disintegrating agents in most tablet
systems are those with the highest water uptake property. In general,
the more hydrophilic, the better disintegrating agents are therefore
highly hydrophilic.
• Lubricant is a substance capable of reducing or preventing friction,
heat, and wear when introduced as a film between solid surfaces.
It works by coating on the surface of particles, and thus preventing
adhesion of the tablet material to the dies and punches.
• Lubricants play more than one role in the preparation of tablets.
• Commonly used lubricants include: talc, magnesium stearat,
calcium stearate ,stearic acid, hydrogenated vegetable oils and
PEG.
Tablet presses:
• single-punch presses
• multi-station rotary presses
Core components:
1. Die
2. lower punch
3. upper punch
The reasons for tablet coating
1.to protect the medicinal agent against
destructive exposure to air and/or humidity;
2.to mask the taste of the drug;
3.to provide special characteristics of drug release;
4.to provide aesthetics or distinction to the
product;
5.to prevent inadvertent contact by nonpatients
with the drug substance
The general methods involved in coating tablets
are as follows
1. Film-coating tablets
2. Entrict Coating
3. Aques Coating
The apparent physical features of compressed tablets:
1. shape: round, oblong, unique
2. thickness: thick or thin
3. diameter: large or small
4. flat or convex
5. coated or uncoated
6. colored or uncolored
7. number of layers.
• Other physical specifications and quality standards:
tablet weight weight variation
content uniformity tablet thickness
tablet hardness tablet disintegration
drug dissolution
• in-process controls
• verification after the production
Tablet hardness
• 1)The greater the pressure applied, the harder the
tablets.
• 2) The hardness required by different tablets
• a) lozenges and buccal tablets: hard (dissolve
slowly)
• b) the tablets for immediate drug release: soft
• 3) Measurement
• a) special dedicated hardness testers
• b) multifunctional equipment
Friability
1) It is used to determine a tablet’s durability
2) Method: allowing the tablets to roll and fall
within the rotating apparatus (friabilator);
determine the loss in weight;
3) requirement: weight loss ≤1%
1) The importance of in vitro dissolution test
a) to guide the formulation and product development
process toward product optimization
b) to monitor the performance of manufacturing
process
c) to assure bioequivalence from batch to batch
d) as a requirement for regulatory approval for product
marketing for products registered with the FDA and
regulatory agencies of other countries.
2) The goal of in vitro dissolution is to provide a
reasonable prediction of the product’s in vivo
bioavailability.
Basis: The combinations of a drug’s solubility and its
intestinal permeability are supposed as a basis for
predicting the likelihood of achieving a successful in
vivo – in vitro correlation (IVIVC).
3) The formulation and manufacturing factors affecting
the dissolution of a tablet
a) the particle size of the drug substance
b) the solubility and hygroscopicity of the formulation
c) the type and concentration of the disintegrant,
binder, and lubricant used
d) the manufacturing method, particularly, the
compactness of the granulation and the compression
force
e) the in-process variables
QUALITY CONTROL(QC) DEPMENTART

Quality control is a procedur or set of procedures interested to

ensure that a manufatured or performed service adheres to a
define set of quality area or meets the requirements of the client or
customer.

Defination:
QUALTY CONTROL (QC) can be defined as a
system of the keeping the desired quality in the
good products by testing the sample agains the set
of criteria
General Principles

1. each holder of manufacturing authorization should have a

QUALITY CONTROL department

2. independence from production and other department is

considered to be fundamental

3. under the authority of an appropriatly qualified and

experienced person with one or several control laboratories his
or her disposal

4. if do not have facility, it can be managed by appointed

respective external laboratories institution
BASIC REQUIREMENTS

Quality control department should have:

 resources:
 adequate facilities
 qualified personnel
 approved written procedures
 tasks
 sampling,inspecting,testing
 releasing or rejecting
 monitority
 objects
 starting materials,intermediate,bulk and finished
products
 returned products
QC Laboratory

 There should be QC laboratory to each manufacturing unit

 The laboratory shall be capable of performing all the test in
accordance to approved specification, or to perform part of
test while sub-contracting part of test approved contact
laboratory
 QC laboratories shall be separated from the production area
especially for microbiology LAB
 THE laboratory should be designed to suit the operation to be
carried out in them. Sufficient space should be given to avoid
mix-ups and cross-contamination. There should be adequate
suitable space for sample and records
 Separate rooms may be necessary to protect sensitive from
vibration, electrical interference, humidity, etc
Responsibilities
 Examine, approves or rejection incoming materials,
intermediates, bulk, the finished product and returned
product
 Does the inspection during the production (in process control)
 Establishes, standardizes, and implements all QC procedures,
and also establish the specification of each incoming
materials.
 Establishes specification of intermediate, bulk and finished
goods together with head of production.
 APPROVES reprocessing instruction and rework instruction
 Review production records to determine error and ensure that
investigations have been conducted and corrective action
taken
 Involved in decision concern with the product quality.
Other rResponsibilities

 Establishing, verification and implementing all QC products

 Evaluating, maintaining, storing and monitoring all reference
and standard retained samples
 Reviewing batch documentation
 Maintain correct specification of materials and finishing
product
 Stability testing of each finished product
 Participating in:
 Complaint investigations
 Environment monitoring
 GMP training
Official and Non official test in QC

 Non-official tests
 Hardness
 Thickness
 Friability
 Official tests
 Weight variation
 Disintegration
 Dissolution
 Drug content
NON-OFFICIAL TEST

I. Hardness
hardness is unofficial test. hardness test means crushing
strength test, it measure crushing strength property defined as
compressional force applied diametrically to a tablet which just
fracture it.

Why do we measure hardness?

 To determine the need for pressure adjustment on the
tableting machine
 Hardness can affect the disintegration. So if the tablet is too
hard, it may not disintegrate in the required period of time.
And if the tablet is so soft it will not withstand the handling
during subsequent processing such a coating or packaging
 In general, if the tablet hardness is too high, we first check its
disintegration test before rejecting the patch, and if it the
disintegration within limit, we accept the patch.
Procedure
 Monsanto tester
the apparatus consist of two jaws facing each holder, one of
which more towards the other. Measurement is carried out on
10 tablets, taking care to remove all the fragments of the
broken tablets before each determine & then take a average
hardness

 Limits
Normal tablet hardness ranges from 4-6kg (Kg= 10 newton),
however, certain tablets as lozenges and buccal tablets that
are intended to dissolve slowly show deliberate higher
hardness values,
Factors affecting the hardness
 Compression of the tablet
 Compressive force
 Amount of binder (more binder means more hardness)
 Method of granulation in preparing the tablet (wet method gives more hardness
then direct method, slugging method gives the best hardness)
 Monsanto tester, pifzer tester, stong cobb hardness tester are manually used &
eweka, casburt hardness tester are motor driven tester
Thickness test
 Thickness s unofficial test.
 Thickness of tablet is inversely proportional to hardness
i.e. Increase in hardness decrease the thickness & vice versa
 Thickness of tablet is measured by Vernier caliper or screw guage
 It is determined for 20 tablets
 For Size and shape of tablet dosage form, the thickness of a tablet is only
variables.
 Thickness of tablet should be controlled within a 5 % of standard value
FRIABILITY

 The tablet may be subjected to a tumbling motion.

for e.g; Coating, packaging, transport, which are mot severe enough to break the
tablet, but may abrade the small particle from tablet surface
 to examine this, tablets are subjected to a uniform tumbling motion for
specified time and weight loss is measured
 Friability is property that is related to the hardness of the tablet & and its also
add weight variation, content uniformity problems.
 It is the tendency of tablets to powder, chip, or fragment and this can affect the
elegance appearance, consumer acceptance of the tablet.
 Friability of a tablet can be determine in laboratory by roche friabilator.
 An instrument called roche friabilator is used to evaluate the ability of the tablet to
withstand abrasion I packaging, handling and shipping

 .
 The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0% of the
tablet weigh are consider acceptable.
 This consist of a plastic chamber that revolves at 25 rpm(roatation per minutes),
dropping the tablets through a distance of six inches in the friabilator , which is
then operate for 100 revolutions.
 20 tablets which are used in weight variation test are also use for friability test.
 Friability must be less than or equal to 1% but if more we do not reject the
tablets as this is non official test
 Perform this test using 20 tablets that were used first in the weight variation
test.
Procedure

 1. weigh 20 tablet together = W1

 2. Put these tablets in the friabilator and adjust the instrument
at 100rpm (i,.e. = 25 rpm for 4 minutes)
 3. weigh the 20 tablets (only the intact ones) = W2

 It must be less than or equal to 1% but if more we do reject

the tablets as this test is non-official
Friability calculation

 table
 So here weight of 20 tablets is W1 = 10093 mg = 10.093 gm
 Now you have to put this 20 tablets in friabilator
 Adjust the instrument at at 100 rpm ( i.e. = 25 rpm for 4 minutes)
 Final weight of the 20 tablets = W2 = 9985 mg = 9.985 gm
 Friability( % loss)
  WEIGHT VARIATION TEST
 Weight variation test is official test.
 Weight 20 tablet selected at random, each one individually. X1, X2, X3,………. Xz
 Determine the average weight. X=(X1+X2+X3+……+Xz)/20
 Limits:
• Upper limit = average weight + ( average weight *% error)
• Lower limit = average weight – ( average weight *%error)
• The individual weights are compared with the upper and lower limits.
• Not more than two of the tablets differ from the average weight by more
than the % error listed, and no tablet differs by more than double that
percentage
WEIGHT VARIATION TOLERANCES

 USP STANDARDS FOR TABLET DOSAGE FORMS

 IP STANDARD FOR TABLET DOSAGE FORM
WEIGHT VARIATION CALCULATION

 TABLE
 Now average weight of tablet is 504.65mg
 So its weight is more than 250 mg so weight variation test allow is
5%
 Now take 5% of 504.65 = 25.23 mg
 Weight variation range is +_ 25.23 mg
 Upper and lower limit of weight variation +_25.23 mg
 Weight range allows is 479.12 to 529.88 mg

Conclusion
 The tablet pass the weight variation test
 If no more than 2 tablets are out side of the percentage limit
 If no tablet differs by more than 2 times the percentage limit.
 Here all are tablets are in limit so test is pass