Transcript Biopharmaceutics Clasification System (BCS)

Biopharmaceutics Classification
System (BCS)
Presented
By
Dr. Sanaa A. El-Gizawy
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The (BCS) has been developed to
provide a scientific approach to allow
for the prediction of in vivo
pharmacokinetics of oral immediate
release (IR) drug products by
classifying drug compounds based on
their solubility related to dose and
intestinal permeability in combination
with the dissolution properties of the
dosage form
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The importance of drug dissolution in the
gastrointestinal tract and permeability
across the gut wall barrier in the oral
absorption process has been well known
since the 1960s, but the research carried out
to constitute the BCS has provided new
quantitative data of great importance for
modern drug development especially within
the area of drug permeability
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According to the BCS, drug substances are
classified as follows:
Class I - High Permeability, High
Solubility
Class II - High Permeability, Low
Solubility
Class III - Low Permeability, High
Solubility
Class IV - Low Permeability, Low
Solubility
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The BCS is a scientific framework for
classifying drug substances based on their
aqueous solubility and intestinal
permeability. When combined with the
dissolution of the drug product, the BCS
takes into account three major factors that
govern the rate and extent of drug
absorption from IR solid oral dosage forms:
dissolution, solubility, and intestinal
permeability.
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CLASS BOUNDARIES
A drug substance is considered HIGHLY
SOLUBLE when the highest dose strength is soluble
in < 250 ml water over a pH range of 1 to 7.5.
A drug substance is considered HIGHLY
PERMEABLE when the extent of absorption in
humans is determined to be > 90% of an
administered dose, based on mass-balance or in
comparison to an intravenous reference dose.
A drug product is considered to be 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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The benefits of knowing the
BCS category of a compound
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
bio-equivalence studies.
The aim of the BCS is to provide a
regulatory tool for the replacement of
certain BE studies by conducting
accurate in vitro dissolution tests.
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Follow; The benefits of knowing the BCS
category of your compound
This step will certainly reduce timelines
in the drug development process, both
directly and indirectly, and reduce
unnecessary drug exposure in healthy
volunteers, which is normally the study
population in BE studies.
It has also been reported that the
application of a BCS strategy in drug
development will lead to significant
direct and indirect savings for
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Follow; The benefits of knowing the BCS
category of your compound
BCS has been developed primarily for
regulatory applications, but it has also
several other applications in both the preclinical and clinical drug development
processes and has gained wide recognition
within the research-based industry
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Combined with the dissolution, the BCS
takes into account the three major factors
governing bioavailability viz. dissolution,
solubility and permeability.
This classification is associated with drug
dissolution and absorption model, which
identifies the key parameters controlling
drug absorption as a set of dimensionless
numbers viz.
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Key Parameters Controlling Drug
Absorption
Absorption number (An), defined as the ratio of
the mean residence time to mean absorption time.
Dissolution number (Dn), defined as the ratio of
mean residence time to mean dissolution time.
Dose number (D0), defined as the mass (Dose)
divided by the product of (uptake volume (250 ml)
and solubility of drug). D0 = Dose/(V.Cs)
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Class I drugs exhibit a high absorption
number and a high dissolution number. The
rate limiting step is drug dissolution.
If dissolution is very rapid, then gastric
emptying rate becomes the rate determining
step.
e.g. Metoprolol, Diltiazem, Verapamil,
Propranolol.
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Class II drugs have a high absorption number but
a low dissolution number. In vivo drug dissolution
is then a rate limiting step for absorption except at
a very high dose number. The absorption for class
II drugs is usually slower than class I and occurs
over a longer period of time.
In vitro- In vivo correlation (IVIVC) is usually
excepted for class I and class II drugs.
e.g. Phenytoin, Danazol, Ketoconazole,
Mefenamic acid, Nifedinpine.
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For Class III drugs, permeability is rate
limiting step for drug absorption. These
drugs exhibit a high variation in the rate and
extent of drug absorption.
Since the dissolution is rapid, the variation
is attributable to alteration of physiology
and membrane permeability rather than the
dosage form factors.
e.g. Cimetidine, Acyclovir, Neomycin B,
Captopril.
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Class IV drugs exhibit a lot of
problems for effective oral
administration. Fortunately, extreme
examples of class IV compounds are
the exception rather than the rule and
are rarely developed and reach the
market. Nevertheless a number of class
IV drugs do exist. e.g. Taxol.
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In vitro/in vivo correlation
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Applications 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.
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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
pharmcokinetic and/or pharmacodynamic 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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Class II Drugs
The systems that are developed for class II
drugs are based on micronisation,
lyophilization, addition of surfactants,
formulation as emulsions and
microemulsions systems, use of complexing
agents like cyclodextrins.
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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.
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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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