Bcs classification by sneha gaurkar

Biopharmaceutic
s classification
system(BCS)
Sneha Gaurkar
M.Pharm II sem
Department of Pharmaceutics
SKBCOP
1

Contents:
• Introduction
• Definition
• Class Boundaries
• Classification
• Biopharmaceutics Drug Disposition
Classification System (BDDCS)
• Significance
• Conclusion
2

Introduction:
• "Biopharmaceutics Classification of Drugs (BCS Classification) is a drug
development tool, that is based on correlation of solubility and permeability
with the bioavailability of drugs.
• This classification system was proposed by Amidon et al (1995).
• BCS classification is a scientific approach for classification of drug substances
and Active Pharmaceutical Ingredients (API’s), based on their aqueous
solubility and intestinal permeability.
• This classification is an important consideration for development of new
dosage form
• Any drug's therapeutic effectiveness is based on it’s bioavailability and
bioavailability is based on drugs absorption and drugs permeability through
biological membrane.
• Thus this classification has considered as important tool for studies and
optimized formulation development.
3

Definition:
The Biopharmaceutical Classification System is a scientific
framework for classifying a drug substance based on its
aqueous solubility, intestinal permeability and dissolution
rate.
4

Class Boundries:
Three major determinations are considered in BCS
classification.
1. Solubility
2. Permeability
3. Dissolution
5

Solubility
 The solubility of a drug substance is the amount of it, that
has passed into solution untill equilibrium is established
and not further drug molecules reach to solution under
any specific temperature or pH.
 According to USFDA BCS guidelines, a drug substance is
considered highly soluble when the highest dose of it is
completely soluble in 250ml or less quantity of aqueous
media over the pH range of 1-7.5. 250ml is considered
because this is approximate volume of water consumed
with orally administered dosage form.
 Whereas according to World Health Organization(WHO)
the same parameters are considered over pH 1.2-7.5.
6

Permeability
 The permeability is a parameter of absorption.
 Permeability is the measurement of the rate of mass
transfer across biological membrane.
 According to USFDA , a drug substance is considered
highly permeable when the extent of the drug absorption
is determined to be 90% or more of an administered dose,
based on mass balance or in comparison to reference
intravenous dose.
7

Dissolution
For dissolution class boundaries, an immediate release
product is considered rapidly dissolving when no less than
85% of the labeled amount of the drug substance dissolves
within 15 minutes using USP Dissolution Apparatus 1 at 100
RPM or Apparatus 2 at 50 RPM in a volume of 900 ml or
less in the following media: 0.1 M HCl or simulated gastric
fluid or pH 4.5 buffer and pH 6.8 buffer or simulated
intestinal fluid
8

Some dimensionless numbers are used in BCS classification:
Absorption Number (An) –
It is defined as ratio of mean residence time to the
mean absorption time.
An = Mean residence time
Mean absorption time
If drug rapidly absorb then absorption time will very
less and absorption number will higher.
9

 Dissolution Number (Dn):
It is defined as ratio of the mean residence time to mean
dissolution time.
Dn = mean residence time
mean dissolution time
if drug rapidly dissolve then dissolution time will very less, and
dissolution number will higher.
 Dose Number (Do):
This is mass divided by the product of uptake volume (250 ml) and
solubility of drug.
Do = mass of drug
Uptake volume X Cs
Cs = Saturation solubility
if the drug has higher solubility then the dose number will be less.
10

Classification :
BCS classes
According to the Biopharmaceutical Classification System
(BCS) drug substances are classified to four classes upon their
solubility and permeability:
Class I - high permeability, high solubility
• Example: metoprolol, paracetamol
• Those compounds are well absorbed and their absorption
rate is usually higher than excretion.
11

Cont….
Class II - high permeability, low solubility
• Example: glibenclamide, bicalutamide, ezetimibe, aceclofenac
• 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 - low permeability, high solubility
• 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 permeability, low solubility
• Example: Bifonazole
• Those compounds have a poor bioavailability. Usually they are not
well absorbed over the intestinal mucosa and a high variability is
expected.
12

Cont...
The table shows the approaches employed to overcome
formulation challenges in each class of drugs.
13

Class Solubility Permeability Rate limiting
factor
I High High Drug dissolution,
but if dissolution is
very fast then
Gastric emptying
time
II Low High Dissolution
III High Low Permeability
IV Low Low Case dependent,
drug modification,
site conditions
BCS classes with their rate limiting factor:
14

Methods to determine class boundaries:
1. Solubility Determination –
Methods for determining drug solubility are –
• Define the pH-solubility profile at different pH conditions
based on the ionization characteristics of the test drug
substance.
•For example, when the pKa of a drug is in the range of 3-5,
solubility should be determined at
pH = pKa, pH = pKa +1, pH = pKa-1,
and at pH = 1 and 7.5.
• At least three determinations for each pH by:
➔ traditional shake-flask method
➔ acid or base titration methods
15

Cont…
2. Permeability Determination
The methods are further classified as –
i)Pharmacokinetic studies in humans:
a)Mass Balance Studies:
Unlabeled, stable isotopes or a radiolabeled drugs
Sufficient number of subjects
Reliable estimate of extent of drug absorption
Highly variable
Not preferred
16

ii) Absolute Bioavailability Studies:
Cont…
Intravenous
administration as
reference
To determine oral BA
When absolute BA ≥90%
Data documenting drug stability in GI fluid not
necessary
17

iii)Intestinal permeability methods:
•In vivo intestinal perfusions studies in humans.
•In vivo or in situ intestinal perfusion studies in animals.
•In vitro permeation experiments with excised human or animal intestinal
tissue.
•In vitro permeation experiments across epithelial cell monolayers
3. Dissolution Determination –
Methods for determining drug product dissolution are –
USP apparatus I (basket) at 100 rpm or USP apparatus II (paddle) at 50
rpm.
Dissolution media (900 ml): 0.1 N HCl or simulated gastric fluid, pH 4.5
buffer, and pH 6.8 buffer or simulated intestinal fluid.
Compare dissolution profiles of test and reference products using a
similarity factor (f2).
18

Similarity Factor f2:
• When comparing dissolution profiles of test & reference
products.
• Not necessary if both ≥ 85 % dissolved in ≤15 minutes in all
three dissolution media.
f2 = 50 • log {[1 + (1/n)∑t=1n(Rt - Tt)²]^-0.5• 100}
Where:
 n is the no. of time points
 Rt is the dissolution value of the reference product at time t
 Tt is the dissolution value of the test product at time t
• Products are considered similar if f2 ≥50
19

Biopharmaceutics Drug Disposition Classification System
(BDDCS)
The major aspects of BCS are the consideration of solubility and
permeation.
 According to BCS, permeability in vivo is considered high when the
active drug is systemically absorbed ≥90%.
Wu and Benet (2005)and Benet et al (2008) have proposed modification
of the BCS system known as the Biopharmaceutics Drug Disposition
Classification System (BDDCS), which takes into account drug metabolism
(hepatic clearance) and transporters in the gastrointestinal tract for drugs
that are orally administered.
 For BCS 1 drugs (i.e., high solubility and high permeability), transporter
effects will be minimal. However, BCS 2 drugs (low solubility and high
permeability), transporter effects are more important.
 These investigators suggest that the BCS should be modified on the
basis of the extent of drug metabolism, overall drug disposition, including
routes of drug elimination and the effects of efflux, and absorptive
transporters on oral drug absorption.
20

Biopharmaceutical Drug Disposition Classification System (BDDCS) and
transporter effects following oral dosing
Class I Class II Class III Class IV
High solubility Low solubility High solubility Low solubility
Extensive
metabolism
Extensive
metabolism
Poor metabolism Poor metabolism
Transporter effect
minimum
Efflux transporter
effects
predominate in
the gut while
absorptive and
efflux transporter
effects occur in
the liver
Absorptive
transporters
effects
predominate (but
maybe
modulated by
efflux
transporters)
Absorptive and
efflux
transporters
effects could be
important
21

Significance or Applications of BCS classification:
Development of Drug Delivery System :
BCS system is based on drug solubility and permeability and
the basis of dosage form development is also the same to achieve
optimized release profile, controlled release and sustain release.
Class I drugs are best suited for controlled release formulation
because they have high solubility and high absorption rate.
Class II drugs are required for some dosage modifications through
drug size reduction (Micronization), use of surfactants,
development of micro emulsion techniques, etc.
22

Cont …
Class III drugs dosage forms are developed through high
frequency capsules, by manipulating gastric retention
time, permeability enhancers, etc, because they have low
permeability.
Class IV drugs are modified through all above mentioned
techniques because they are less soluble and less
permeable.
23

BIOWAIVER “in vitro instead of in vivo bioequivalence testing”
Definition: It is an exemption from conducting human bioequivalence
studies when the active ingredients meet certain solubility and
permeability criteria in vitro and when the dissolution profile of the
dosage form meets the requirements for an IR dosage form.
CRITERIA OF BIOWAIVER:
 Rapid and similar dissolution
High solubility
 High permeability
 Wide therapeutic window
 Excipient used in dosage form are same as those present in approved
drug product
24

BCS Bio-waivers:
BCS classification is effective tool to reduce the time and
cost of approval of drug products from FDA and WHO etc.
Certain products are exempted or waived (are called Bio-
waivers) from various in-vivo bioavailability and/or
bioequivalence studies may be waived (not considered
necessary for product approval).
Instead of conducting expensive and time consuming in-vivo
studies, the test products are considered same with
reference product, if the test product show similar in-vitro
dissolution and solubility profile.
BCS based bio-waivers are suitable for development of
immediate release solid dosage forms.
25

CONCLUSION:
•Biopharmaceutical classification system aims to provide
regulatory tools for replacing certain bio-equivalence
studies by accurate in vivo dissolution tests.
•The in vivo pharmacokinetics of drug depends largely on
the solubility and permeability.
• Many laboratories are engaged to find better means to
estimates in vivo behavior of the drug after oral
administration by using simple in vitro dissolution tests
26

References:
•Brahmankar, D. M and Jaiswal, Sunil. B (2009). Biopharmaceutics
and Pharmacokinetics – A Treatise. Vallabh Prakashan, Page no. 287-
289.
•Leon shargel, Susanna wu-pong, Andrew B.C.Yu , Applied
Biopharmaceutics & Pharmacokinetics, 7th edition , published by the
Mc Graw hills companies, page no. 507 to 509.
•https://youtu.be/U2KnRYS-rh8
•www.wikipedia.com
•https://www.slideshare.net/drshereenshehata/biopharmaceutics-
classification-system-71410439
27

Bcs classification by sneha gaurkar

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