The document discusses the Biopharmaceutics Classification System (BCS) and biowaivers. It begins by explaining per oral drug administration and factors affecting oral drug absorption like solubility, permeability, and dissolution. It then covers the Lipinski rule of five, BCS classification parameters, and four drug classes. Class boundaries and criteria for biowaivers are outlined. Biowaivers can save time and money by waiving bioequivalence studies for drugs that meet BCS criteria of being highly soluble and permeable. The significance of biowaivers in drug development is also highlighted.

1. BCS Insight and Biowaiver
Application
Miss. S. N. Biradar
M. Pharm in Pharmaceutics ( Sem-I )
Guide - Dr. V.S.Kashikar
Dept. of Pharmaceutics
Modern College of Pharmacy (For Ladies),
Moshi.
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2. Per oral Administration
• Defination:- It is a route of administration where a drug
is taken through mouth.
• Per oral administration is the predominant route of drug
administration due to its benefits such as
 Self administration with minimal discomfort to patients
 Improved patient compliance
 Cost effective
 Flexibility in design of dosage form
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3. Movement of Drug through the GI Tract
Mouth
Stomach
(digestive enzyme)
pH 1.5 to 3.5
Small Intestine
(duodenum,
jejunum, ileum)
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4. Drug exerts its pharmacological effect only when it
binds to specific receptor , for which it should be in its
solubilized form and then should be able to transverse
the intestinal barrier.
Thus Solubility, Dissolution, Permeation are the major
rate limiting steps & are the key parameter.
Solubility : The amount of solute particle dissolved into
solvent at a given temperature and pressure.
Permeability : The ability of drug molecules to
permeate through a mucosal barrier into the systemic
circulation.
Dissolution : The transfer of molecules or ions from a
solid state into solution is known as Dissolution.
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5. Factor affecting Oral Drug Absorption
Physiological Formulation Physiochemical
factor factor factor
Membrane physiology Solubility
Passage of drug across Permeability
membrane Surface area
GI physiology Particle size
Lipophilocity
pH
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6. Lipinski Rule of Five
 Physicochemical properties of a drug such as
lipophilicity and solubility are the key properties which
are affected by :
Molecular weight
H- bonding
pKa
Molecular shape
Amphiphilicity
• Limitation :-
It can holds for molecules which are not substrate of
active transporter
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7.  Lipinski Rule of 5 which state that poor absorption of a
compound is more likely when its structure is
characterized by :
Molecular Weight ˃ 500 Da
clogP ˃ 5 (octanol-water partition coefficient)
MlogP ˃ 4.15 (Multi-core LogP)
H-bonding donor ˃ 5
H-bonding acceptor ˃ 10
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8. Biopharmaceutics Classification System
 BCS is a scientific framework for classifying drug
substances based on their aqueous solubility and
intestinal permeability.
 It is a drug development tool that allows estimation of
the contribution of solubility, dissolution and intestinal
permeability affect that oral drug absorption.
 Key parameters are characterized in BCS classification
are :
1. Absorption number (An)
2. Dissociation number (Dn)
3. Dose number (Do)
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9.  Absorption No. (An) :- It is the ratio of Radial
Absorption to Axial Convection Rate .
An ˃ 1 → indicate Complete absorption
 Dissolution No. (Dn) :- The time required for drug
dissolution which is the ratio of intestinal residence time
to the dissolution time.
Higher the Dn → Higher fraction dose absorbed.
Dose No. (Do):- It is the ratio of dose concentration to
drug solubility.
Do ≤ 1→ higher solubility.
Do ˃ 1→ low solubility.
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10. Class Boundaries
 HIGHLY SOLUBLE:- The highest dose strength
should be soluble in < 250 ml water over a pH range of
1 to 7.5.
(The volume estimated-a glassful i.e. 8 ounce)
 HIGHLY PERMEABLE:- When the extent of
absorption in humans is determined to be > 90% of an
administered dose.
 RAPIDLY DISSOLVING :- When > 85% of the
labeled amount of drug substance dissolves within 30
minutes using USP apparatus I or II in a volume of <
900 ml buffer solutions
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11. BCS CLASSIFICATION
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12. Biowaiver
 The term Biowaiver is applied to a regulatory drug
approval process when the drug dossier is approved
based on the evidence of equivalence other than through
in vivo equivalence testing.
 In 1995 the American Department of Health & Human
Service US Food & Drug Administration (HHS-FDA)
instigated the Biopharmaceutics Classification System
(BCS), with the aim of granting so-called biowaivers for
SUPACs.
 BCS provides biowaivers for Class 1, II, III drugs with
some specification.
 As the BCS is only applicable to APIs which are
absorbed from the small intestine;
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13.  A Biowaiver means that in vivo bioavailability
and/or bioequivalence studies may be waived
(i.e. not considered necessary for product
approval).
Bioavailability :- It means the rate and extent to which
the active drug substance is absorbed from a
pharmaceutical dosage form and becomes available at
the site of action.
Bioequivalence :-It refers to the drug substance in two or
more identical dosage forms, reaches systemic
circulation at the same rate and to the same relative
extent.
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14.  Criteria for Biowaiver (by USFDA BCS guideline)
 Immediate-release solid oral dosage form
 Rapid and similar dissolution.
 High solubility & High permeability.
 Wide therapeutic window.
 Excipients used in dosage form are same as those
present in approved drug product
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15. Significance of Biowaiver
 It can save both time and money—if the immediate -
release, orally administered drug meets specific criteria,
the FDA will grant a waiver for expensive and time-
consuming bioequivalence studies.
 Valuable tool for formulation scientist for selection of
design of formulated drug substance.
 When integrated with other information provide a
tremendous tool for efficient drug development.
 Reduces cost and time of approving Scale- up and post
approval challenges.
 Applicable in both pre-clinical and clinical drug
development process.
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16. Literature survey
Sr.
No.
Title Abstract Author
1. Understanding per oral
absorption: regulatory
aspects and contemporary
approaches to tackling
solubility and permeability
hurdles
BCS; Solubility;
Permeability;
Formulation
strategies;
Factors
affecting
absorption
Prachi B.
Shekhawat,
Varsha B.
Pokharkar
2. Computational-Regulatory
Developments in the
Prediction
of Oral Drug Absorption
· Bioavailability G. Valsami and
P. Macheras
3. Prediction of Solubility and
Permeability Class
Membership: Provisional
BCS
Classification of the World’s
Top Oral Drugs
BA/BE;
biopharmaceuti
cs classification
system;
biowaiver;
intestinal
Arik Dahan,
Jonathan M.
Miller, and
Gordon L.
Amidon
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17. 4. Biopharmaceutics
Classification System
Biopharamceutics
classification system
Biowaiver
Permeability
Dissolution
Solubility
Chavda HV,
Patel CN1,
Anand IS2
5. BIOWAIVERS:
CRITERIA AND
REQUIREMENTES
The aim of biowaiver
guidance is to reduce the
risk of bioinequivalence
to an acceptable level.
Prepared by Dr.
Mazen Kurdi
Reviewed by Dr.
Rita Karam
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18. Reference
1. Shekhawat P, Pokharkar V, Understanding peroral absorption:
regulatory aspects and contemporary approaches to tackling
solubility and permeability hurdles, Review Article, Acta
Pharmaceutica Sinica B, 2017, Volume 7, Page no. 260-280.
2. Dahan A, Miller J, Amidon G , Prediction of Solubility and
Permeability Class Membership: Provisional BCS Classification
of the World’s Top Oral Drugs , Review Article , American
Association of Pharmaceutical Scientists, 2009 , Volume 11, Page
no.740 – 746.
3. Chavda H, Patel C, Anand I, Biopharmaceutics Classification
System, Review Article , Sys Rev Pharm, 2010, Volume 1, Page
no. 62-69.
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19. 4. Valsami G, Macheras P, Computational-Regulatory Developments
in the Prediction of Oral Drug Absorption, Review Article , Wiley
VCH Verlag GmbH & Co. KGaA, Weinheim , 2011, Page no. 112-
121.
5. Murakami T, Absorption sites of orally administered drugs in the
small intestine, Review Article, Informa UK Limited, trading as
Taylor & Francis Group, 2017
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