Biopharmaceutic Classification System(BCS) of drugs & Tablet formulation

1. Pharmaceutical Technology-II
Assignment on :
Biopharmaceutic Classification System(BCS) of
drugs
&
Tablet formulation
Submitted to :
Mr. Md. Saiful Islam Pathan
Associate Professor, Department of Pharmacy
State university of Bangladesh
1
Submitted by :
Md. Reyaz Ahamed(UG08-21-12-007)
Tasmia Tabassum(UG08-21-12-003)
State University of Bangladesh. (Department of Pharmacy ).Batch: 21 A

2. Biopharmaceutics Classification System
(BCS)
Biopharmaceutics is concerned with factors that
influence the rate of drug absorption. The factors that
affect the -
- release of a drug from its dosage form,
- its dissolution into physiological fluids,
- its stability within those fluids,
- its permeability across the biological membrane and
- its presystemic metabolism will influence its rate and
extent of absorption.
Once the drug is absorbed into the systemic circulation , its
distribution within the body tissue (including to its site
of action), its metabolism and elimination are described
by the pharmacokinetics of the compound.
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3. The key biopharmaceutical properties that can be
quantified and therefore give an insight into the
absorption of a drug are its:
Release of drug from its dosage form into solution at
the absorption site.
Stability in physiological fluids.
Permeability across the biological membrane.
Presystemic metabolism.
3

4. Introduction of Biopharmaceutics Classification System
(BCS)
The Biopharmaceutics Classification System (BCS) is
a scientific framework for classifying drug substances
based on their aqueous solubility and intestinal
permeability. The principle of the BCS is that if two
drug products yield the same concentration profile along
the gastrointestinal (GI) tract, they will result in the
same plasma profile after oral administration. This
concept can be summarized by the following equation:
J = PwCw
where, J is the flux across the gut wall, Pw is the
permeability of the gut wall to the drug and Cw is the
concentration profile at the gut wall.
4

5. According to BCS, drug substances or APIs are
divided into high/low solubility and permeability classes
as follow:
Class I : High Solubility - High Permeability
Class II : Low Solubility - High Permeability
Class III : High Solubility - Low Permeability
Class IV : Low Solubility - Low Permeability
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6. 6

7.  Class I drugs exhibit a high dissolution number & high
absorption number . That’s why this drugs rapidly transported
across the gut wall.
e.g. β – blockers(propranolol & metaprolol).
 Class II drugs have a low dissolution number but a high
absorption number . The absorption for Class II drugs is usually
slower than Class I and occurs over a longer period of time.
e.g. Non-steroidal anti-inflammatory drugs.
 Class III drugs, dissolve rapidly but which are slow to permeate
the gastrointestinal epithelium, are in contact with it.
e.g. H2-antagonist & β-blocker(atenolol) .
 Class IV drugs are those that are classed as poorly soluble &
poorly permeable. They have a poor oral bioavailability. That’s
why they can not given by the oral route.
e.g. Thiazide diuretics.
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8. Table : Examples of some drugs as per biopharmaceutical classification
system
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9. Class Boundaries:
The drugs are classified in BCS on the basis of
following parameters:
1. Solubility
2. Permeability
3. Dissolution
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10. The class boundaries for these parameters are:
1. Solubility class boundaries- It is based on the highest
dose strength of an immediate release (IR) product. A
drug is considered highly soluble when the highest
dose strength is soluble in 250 ml or less of aqueous
media over the pH range of 1 to 7.5.
2. Permeability class boundaries- A drug substance is
considered highly permeable when the extent of
absorption in humans is determined to be 90% or more
of the administered dose based on a mass-balance
determination or in comparison to an intravenous dose.
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11. 3. Dissolution class boundaries- A drug product is
considered to be RAPIDLY DISSOLVING when > 85%
of the labeled amount of drug substance dissolves within
30 minutes using USP dissolution apparatus I or II in a
volume of 900 ml or less in the following media:
 0.1 N HCl or simulated gastric fluid or
 Mix phosphate buffer pH 6.8 or simulated
intestinal fluid.
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12. Tablet Formulation
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13. Introduction of Tablets
Definition: Tablets are defined as unit dose, solid
preparations containing one or more active ingredients.
Tablets are obtained by compressing uniform volumes of
particles.
Most of time powders must be converted to granules.
13

14.  They are mainly intended for oral administration.
 Some are Swallowed whole (Conventional)
 Some are being chewed (Chewable)
 Some are dissolved or dispersed in water before being
administered (Dispersible/Effervescent)
 Some are retained in the mouth, where the active
ingredient is 'liberated'. (Buccal & Sublingual)
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15. Advantages of Tablets
 Tablets are convenient to use and are an elegant dosage
form.
 Offers a range of drug release rates and durations of
clinical effect.
 Tablets may be formulated to offer rapid drug release or
controlled drug release.
 Gives formulator choice to release the therapeutic agent
at a particular site within the gastrointestinal tract
- To reduce side effects.
- To promote absorption at that site and.
-To provide a local effect.
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16.  Physical or chemical incompatible active pharmaceutical
substances can be incorporated.
 Easier to mask the taste of bitter drugs.
 The chemical, physical and microbiological stability.
 Inexpensive dosage form.
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.
 Coating can mask unpleasant tastes & improve patient
acceptability.
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17. Disadvantages of Tablets
 It requires a series of unit operations, causing increased
level of product loss.
 The absorption dependent on physiological factors,
e.g. gastric emptying rate, and shows inter patient variation.
 The compression properties of certain therapeutic agents
are poor.
 Impose problem for administering in children and the
elderly difficulties in swallowing.
 In case of unconscious patient it can not be administered.
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18.  Drugs with poor wetting, slow dissolution, intermediate
to large dosages may be difficult or impossible to
formulate and manufacture as a tablet that provide
adequate or full drug bioavailability.
 Bitter taste drugs, drugs with an objectionable odor, or
sensitive to oxygen or moisture may require
encapsulation or entrapment prior to compression or the
tablets may require coating.
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19. Types of Tablets
On the basis of coating, tablet may be-
1. Uncoated or
2. Coated
Uncoated Tablets:
 chewable tablet,
 effervescent tablet,
 lozenge tablet,
 soluble tablet and
 sublingual tablet.
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Coated tablets:
 enteric coated tablet,
 film coated tablet,
 implant,
 sugar coated tablet and
 modified-release tablet.

20. 20
On the basis of Route of administration
 Oral tablets
 Sublingual or buccal tablets
 Vaginal tablets
On the basis of Production process
 Compressed tablets
 Multiple compressed tablets
 Tablet within a tablets: core and shell
 Multilayer tablet

21. Additives used in tablets
 Drugs (Active pharmaceutical ingredient (API):
Example: paracetamol, aspirin, diclofenac, metformin,
telmisartan, nimesulide , nifedipine etc.
 Diluents:
Act as fillers used to make required bulk of the tablet.
A diluent should have following properties:
 Non toxic
 Commercially available in acceptable grade
 Low in cost
 Physiologically inert
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22.  Physically & chemically stable by themselves & in
combination with the drugs.
 Free from all microbial contamination.
 Do not alter bioavailability of drug.
 Color compatible
Commonly used tablet diluents:
• Microcrystalline cellulose-Avicel (PH 101 and PH 102)
• Dibasic calcium phosphate dehydrate
• Calcium sulphate dihydrate
• Mannitol
• Sorbitol
• Sucrose
• Dextrose, etc.
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23.  Binders:
Binders hold the ingredients in a tablet together
Examples:
Acacia, tragacanth,Cellulose derivatives- MC, HPC,
HPMC(Hydroxypropyl methylcellulose).
Gelatin, Glucose,Polyvinylpyrrolidone (PVP), Starch
paste, Sodium alginate , sorbitol , etc.
 Disintegrants
Added to facilitate disintegration when comes in contact
with water in the GIT.
Example:
Starch, Cellulose derivatives- CMC-Na (sodium carboxy
methyl cellulose), PVP (Polyvinylpyrrolidone)
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24.  Lubricants
Lubricants prevent ingredients from clumping together and
from sticking to the tablet punches or capsule filling
machine.
Example: Stearic acid, Magnesium stearate, Talc,
PEG (Polyethylene glycol), Surfactants.
 Glidants
Glidants are intended to promote flow of granules or
powder material by reducing the friction between the
particles.
Example: Corn Starch , Talc , Silica
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25.  Antiadherants
Reduce the adhesion between the powder (granules) and
the punch faces and thus prevent tablet sticking to the
tablet Punches. e.g. Magnesium stearate, Talc
 Preservatives
Examples: Citric acid and sodium citrate, methyl and
propyl paraben.
 Coloring agents:
Example: FD & C color.
 Flavoring agents:
For chewable tablet- flavor oil are used
 Sweetening agents:
For chewable tablets: Sugar, mannitol.
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26. 26

27. 27
The main process of tablet formulation is granulation.
Granulation
A size enlargement process which converts small
particles into physically stronger & larger agglomerates.
Granulation method can be broadly classified into
two types:
 Wet granulation
 Dry granulation

28. Pharmaceutical Granulation
Equipment
Wet granulators:
There are three main types of granulator used in the
pharmaceutical industry for wet granulation.
 Shear granulators
 High-speed mixer/granulators
 Fluidized-bed granulators
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29. Shear Granulators
 The mixed powders are
fed into the bowl of the
planetary mixer and
granulating liquid is added
as the paddle of the mixer
agitates the powders.
 The planetary action of
the blade when mixing is
similar to that of a
household mixer
29

30. High-speed mixer/granulators
 This type of granulator (e.g. Diosna, Fielder) is used
extensively in pharmaceutics.
 The machines have a
-Stainless steel mixing bowl containing a three-bladed
main impeller, which revolves in the horizontal plane,
-Three-bladed auxiliary chopper (breaker blade) which
revolves either in the vertical or the horizontal plane.
 The unmixed dry powders are placed in the bowl and
mixed by the rotating impeller for a few minutes.
 Granulating liquid is then added via a port in the lid of
the granulator while the impeller is turning.
 The granulating fluid is mixed into the powders by the
impeller. 30

31.  The chopper is
usually switched
on when the
moist mass is
formed, as its
function is to
break up the wet
mass to produce a
bed of granular
material.
31

32. 32
Figure: High-speed mixer/granulators

33. Fluidized-bed granulators
 The powder particles are fluidized in a stream of air, but in
addition granulation fluid is sprayed from a nozzle on to the
bed of powders.
 Heated and filtered air is blown or sucked through the bed of
unmixed powders to fluidize the particles and mix the
powders; fluidization is actually a very efficient mixing
process.
 Granulating fluid is pumped from a reservoir through a spray
nozzle positioned over the bed of particles.
 The fluid causes the primary powder particles to adhere when
the droplets and powders collide.
 Escape of material from the granulation chamber is prevented
by exhaust filters, which are periodically agitated to
reintroduce the collected material into the fluidized bed.
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34. 34

35. Dry granulators
Sluggers:
 Dry powders can be compressed using a conventional
tablet machine or, more usually, a large heavy duty rotary
press can be used.
 This process is often known as 'slugging',
 A hammer mill is suitable for breaking the compacts.
Roller compactors:
 Powder mix being squeezed between two rollers to form a
compressed sheet
 The sheet normally is weak and brittle and breaks
immediately into flakes.
 These flakes need gentler treatment to break them into
granules, and this can usually be achieved by screening
alone. 35

36. Figure: Dry granulators 36

37. Methods of tablet manufacture
There are three basic methods of preparation of
compressed tablets.
 Wet granulation
 Dry granulation
 Direct compression
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38. Unit
Operation
Wet granulation Dry granulation Direct compression
1. Dispensing/Weighing Dispensing/Weighing Dispensing/Weighing
2. Sieving/Milling Sieving/Milling Sieving/Milling
3. Dry powder mixing Dry powder
mixing/Lubrication
Dry powder
mixing/Lubrication
4. Wet massing with addition
of granulating fluid
Roller
compaction/Slugging
Compression
5. Wet screening Milling/Crushing
6. Drying Compression
7. Dry screening after
checking LOD
8. Lubrication
9. Compression 38

39. Tablet manufacturing
Four basic requirements for successful tablet production:
 Design
 Equipments
 Facility
 Personnel
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40. Tablet manufacturing(contd….)
 Tablets are made by compressing a formulation
containing drug or drugs with excipients on stamping
machine called Presses.
 Tablet compression machines are designed with
following basic components.
 Hopper- for holding and feeding granulation to be
compressed.
 Dies- that define size and shape of tablets.
 Punches- for compressing granulation within die.
 Cam tracks- for guiding movement of punches.
 Feeding mechanism- for moving granules from hopper
in to die.
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41. Tablet manufacturing(contd….)
 Tablet presses are classified as either
 Single punch or
 Multi station rotary presses.
Single punch machine are called as stamping press as all of
the compression force is applied by upper punch.
Multi-station presses are termed rotary because the head of
tablet machine that holds upper punches , dies and lower
punch in press rotates.
 The ultimate test of a tablet formulation and granulation
process is whether the granulation can be compressed on
a high-speed tablet press.
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42. Figure: Single punch presses
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43. Figure: Multi station rotary presses. 43

44. Tablet manufacturing(contd….)
 During compression, the tablet press performs the
following functions:
 Filling of empty die cavity with granules.
 Precompression of granulation (optional).
 Compression of granules.
 Ejection of the tablet from the die cavity and take-off of
compressed tablet.
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45. Thank you
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