This presentation provides a detailed information about Biopharmaceutics classification system(BCS) and its significance on dissolution study as well as its application in dosage form development.

1. BIOPHARMACEUTICS CLASSIFICATION
SYSTEM (BCS);
ITS SIGNIFICANCE ON DISSOLUTION
STUDY &
APPLICATION IN DOSAGE FORM
DEVELOPMENT
1
Guided By:-
Dr. R. D. PARMAR
DEPARTMENT OF
PHARMACEUTICS
B.K.M.G.P.C.
RAJKOT-360005
PReSeNTed By:-
SAGAR Y. GODA
M.PHARM.: - I
ROLL NO: 03
EN NO: 162120808005
(2016-17)

2. • Introduction to BCS
• Objective of the BCS
• Classification of drugs as per BCS
• Class boundaries
• Applications of BCS
• Exception for BCS
• Extension to BCS
• Conclusion
• Reference
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3. The Biopharmaceutics Classification System (BCS) was
proposed in 1995 by Amidon . It is a scientific framework
which divides APIs into four groups, according to their
solubility and permeability properties.
This approach is meant to reduce unnecessary in vivo
bioequivalence studies however, is restricted to non-
critical drug substances in terms of solubility,
permeability, and therapeutic range, and to non-critical
pharmaceutical forms.
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4. To improve the efficiency of the drug development and
review process by recommending a strategy for
identifying expendable clinical bioequivalence test.
To recommend a class of immediate-release (IR) solid
oral dosage forms for which bioequivalence may be
assessed based on in vitro dissolution tests.
To recommend methods for classification according to
dosage form dissolution along with the solubility–
permeability characteristics of the drug product.
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5.  According to the BCS, drug substances are classified as follows
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Class 1: High Solubility – High
Permeability
Class 2: Low Solubility - High
Permeability
Class 3: High Solubility - Low
Permeability
Class 4: Low Solubility - Low
Permeability

6. • Class I - High Solubility, High Permeability
– Example: metoprolol
– Those compounds are well absorbed and their absorption rate is
usually higher than excretion.
• Class II – Low Solubility, High Permeability
– Example: Glibenclamide
– The bioavailability of those products is limited by their solvation rate.
A correlation between the in vivo bioavailability and the in vitro
solvation can be found.
• Class III – High Solubility, Low Permeability
– Example: Cimetidine
– The absorption is limited by the permeation rate but the drug is
solvated very fast. If the formulation does not change the
permeability or gastro-intestinal duration time, then class I criteria
can be applied.
• Class IV - Low Solubility, Low Permeability
– Example: Hydrochlorothiazide
– Those compounds have a poor bioavailability. Usually they are not
well absorbed over the intestinal mucosa and a high variability is
expected. 6/18

7.  HIGHLY SOLUBLE:
When the highest dose strength is soluble in < 250 ml water over a pH range of 1 to
7.5.
 HIGHLY PERMEABLE:
When the extent of absorption in humans is determined to be > 90% of an
administered dose
 RAPIDLY DISSOLVING:
When no less than 85% of the labeled amount of the drug substance
dissolves within 30 minutes, using U.S. Pharmacopeias (USP) Apparatus I at
100 rpm (or Apparatus II at 50 rpm) in a volume of 900 ml or less in each of
the following media:
(1) 0.1 N HCl or Simulated Gastric Fluid USP without enzymes
(2) a pH 4.5 buffer;
(3) a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes
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8. • BCS is widely used in design and development of innovation drugs, new
dosage forms (Permeability amplifiers), in clinical pharmacology (drug-
drug, drug-food interaction) and also by regulation agencies of several
countries as the scientific approach, for testing of waivers on
bioavailability. Given below the application of BCS in different fields:
• 1. Application of BCS in Oral Drug Delivery Technology
Once the solubility and permeability characteristics of the drug are known it
becomes an easy task for the research scientist to decide upon which drug
delivery technology to follow or develop.
Class-I Drugs
• The major challenge in development of drug delivery system for class I
drugs is to achieve a target release profile associated with a particular
pharmacokinetic and/or pharmacodynamics profile. Formulation
approaches include both control of release rate and certain
physicochemical properties of drugs like pH-solubility profile of drug.
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9. • Class-II Drugs
The systems that are developed for class II drugs are based on
micronisation, lyophilization, and addition of surfactants, formulation
as emulsions and microemulsions systems and use of complexing
agents like cyclodextrins.
• Class-III Drugs
Class III drugs require the technologies that address to fundamental
limitations of absolute or regional permeability. Peptides and proteins
constitute the part of class III and the technologies handling such
materials are on rise now days.
• Class-IV Drugs
Class IV drugs present a major challenge for development of drug
delivery system and the route of choice for administering such drugs
is parenteral with the formulation containing solubility enhancers.
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10. BCS ClaSS Formulation
High solubility high permeability
Low solubility high permeability
High solubility low permeability
Low solubility low permeability
Simple capsule or tablet
Micronized API and surfactant
Nano-particle technology
Solid dispersion
Coating technology
Liquid or semisolid filled capsule
Melt granulation/extrusion
Simple capsule or tablet
Absorption enhancers
Combination of BCS 2 and absorption
enhancers 10/18

11. 11/18

12. 2. Application of BCS in New Drug Application (NDA) and
Abbreviated New Drug Application (ANDA)
The principles of the BCS classification system can be applied to NDA
and ANDA approvals as well as to scale-up and post approval changes
in drug manufacturing. A waiver of In-vivo Bioavailability and
Bioequivalence studies based on the BCS classification can therefore
save pharmaceutical companies a significant amount of development
time and reduce development costs.
3. Application of BCS in optimization of new chemical entity
The pharmacokinetic idea of new chemical entity which is already
synthesized or identified and has therapeutic value but still under
investigation for formulation development and final approval can be
provided by BCS. The BCS provide an opportunity to the synthetic
chemist to manipulate in the chemical structure in the chemical entity in
order to optimize the physicochemical properties of lead molecule for
desired delivery and targeting through High Throughput Pharmaceutics
(HTP).( Jorgensen W. L. et al, 2002 and Lobel L. M. et al, 2003)
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13. BIOWAIVERS
In simple word exemption of clinical bioequivalence study of drug product.
BCS gives biowaivers for only class-I drugs.
Following criteria are recommended for justifying the request for a
waiver of in-vivo bio-studies.
1. Highly soluble and highly permeable (class I drugs).
2. An immediate release (IR) drug product.
3. Dissolution should be greater than 85% in 30 minutes in the 3 recommended
dissolution media
4. The drug should not be a narrow therapeutic index drug.
5. Excipient used should have been previously used in a FDA approved IR solid
dosage forms. The quantity of excipient in IR product should be consistent
with their intended function.
6. The drug must be stable in gastro intestinal tract
7. Product is designed not to be absorbed in oral cavity.
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14.  BCS-based biowaivers are not applicable for the following:
1. Narrow Therapeutic Range Drugs
 This guidance defines narrow therapeutic range drug products as
those containing certain drug substances that are subject to
therapeutic drug concentration or pharmacodynamic monitoring, and
/or where product labeling indicates a narrow therapeutic range
designation. Examples include digoxin, lithium, phenytoin,
theophylline, and warfarin.
 Because not all drugs subject to therapeutic drug concentration or
pharmacodynamic monitoring are narrow therapeutic range drugs,
sponsors should contact the appropriate review division to determine
whether a drug should be considered to have a narrow therapeutic
range.
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15. 2. Products Designed to be absorbed in the Oral Cavity
A request for a waiver of in vivo BA/BE studies based on the
BCS is not appropriate for dosage forms intended for
absorption in the oral cavity (e.g. sublingual or buccal tablets).
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16. • Bergstrom et al. in 2003 devised a modified Biopharmaceutical
Classification System, in which they categorized the drugs into six
classes based on the solubility and permeability. The solubility was
classified as "high" or "low" and the permeability was allotted as
"low", "intermediate," or "high".
• This new classification was developed based on the calculated
surface area descriptors on the one hand and solubility and
permeability on the other. Surface areas related to the nonpolar part
of the molecule resulted in good predictions of permeability. It was
tentatively concluded that these models would be useful for early
indication with regard to the absorption profiles of the compound
during the early stages of drug discovery so that the necessary
modifications can be made to optimize the pharmacokinetic
parameters.
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17.  Poor solubility and poor permeability account for many
pharmacokinetic failures and about thirty percent of drug molecules
are rejected due to pharmacokinetic failures.
 When poor pharmaceutical properties are discovered in
development, the cost of bringing a potent, but poorly absorbable
molecule to the product stage by formulation can become very high.
Fast and reliable in vitro prediction strategies are needed to filter out
problematic molecules at the earliest stage of discovery.
 This communication will consider recent developments in
physiochemical profiles used to identify molecules with physical
properties related to good oral absorption. FDA's biopharmaceutical
classification system (BCS) is an attempt to rationalize the critical
components related to oral absorption and utilization of these
principles for selection of a suitable technology to serve the interests
of the early stages of drug discovery.
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18. 1. Biopharmaceutics & Pharmacokinetics by D.M.Bramankar
2.Journal of Current Pharmaceutical Research 2011; 5 (1): 28-31
3. International Journal of PharmTech Research CODEN (USA): IJPRIF
ISSN : 0974-4304 Vol.2, No.3, pp 1681-1690, July-Sept 2010
4. Guidance for Industry Waiver of In Vivo Bioavailability and
Bioequivalence Studies for Immediate-Release Solid Oral Dosage
Forms Based on a Biopharmaceutics Classification System ,U.S.
Department of Health and Human Services Food and Drug
Administration, Center for Drug Evaluation and Research (CDER)
August 2000
5. Guidance for Industry “Waiver of In vivo bioavailability and
bioequivalence studies for immediate release solid oral dosage forms
based on BCS”
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