Biopharmaceutics
Classification System
MET IOP NASHIK
(BCS)
MPP
Dr. M. P. Patil
MET IOP, Nashik
• 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
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rate and extent of drug absorption from IR solid oral dosage
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forms:
• Dissolution
• Solubility and
• Intestinal permeability.
Class Solubility Permeability
Class I High High
Class II Low High
Class III High Low
Class IV Low Low
1.Solubility
• Highly soluble: highest single therapeutic dose is
completely soluble in 250 ml or less of aqueous media.
• pH range: 1- 6.8 at 37±1oC
• Solubility determination:
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• pH is based upon ionization characteristics of drug
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substance.
• pH = pKa, pH = pKa + 1, pH = pKa - 1, and at pH = 1 and
6.8.
• Determined by shake-flask technique.
• A minimum of three replicate determinations at each
solubility condition/pH using validated stability-indicating
method.
• Degradation as a function of pH should be reported.
• The volume of medium used is 250 (8 fl. Ounce glass of
• The highest strength divided by 250 should be less than or
equal to the lowest solubility over the pH range of 1 - 6.8 –
Highly soluble substance.
2.Permeability
• It should be based on the extent of absorption i.e. fraction of
dose absorbed and directly measures rate of mass transfer
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across the intestinal membrane.
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• High permeability :
• When ≥85% of administered dose is absorbed (absolute BA);
• When ≥85% of administered dose is excreted unchanged in
urine or
• When ≥85% of administered dose is excreted as metabolite
in urine with evidence of stability.
• Using excised human or animal intestinal tissues.
• Additionally permeability characteristics is generated using
octanol: water partition coefficient.
3.Dissolution:
• IR product - Rapidly dissolving: when
• 85% or more of the labelled amount of drug substance
dissolves within 30 minutes (15 min. for very rapid
dissolving)
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• USP I @ 100 RPM and USP II @ 50 RPM.
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• 500 mL or less media (if 900 mL; with justification).
• Media – 0.1 N HCl / simulated gastric fluid without enzyme,
buffer pH 4.5 and buffer pH 6.8 / simulated intestinal fluid
without enzyme.
• For coated tablet and capsules - SGF and SIF with enzyme.
• Using aforementioned experimental conditions, dissolution
characteristics are generated.
• Similarity factor (f2)
• A minimum of 12 dosage units of the test and reference drug
product.
• Sufficient number of sample point (5,10,15,30,45,60
minutes).
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• Only one measurement should be considered after 85%
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dissolution of both products
• CV should not be more than 20 percent at the earlier time at
10% at other points.
f2 = 50 - 100
• Class Examples
Class I Metoprolol, Diltiazem, Verapamil, Propranolol
Class II Glipizide, Gliclazide, Indomethacin, Griseofulvin,
Itraconazole
Class III Cimetidine, Acyclovir, Neomycin B, Captopril
Class IV Chlorthiazide, Amphotericin B, Colistin, Chlorthalidone
References
• Waiver of In Vivo Bioavailability and Bioequivalence Studies
for Immediate-Release Solid Oral Dosage Forms Based on a
Biopharmaceutics Classification System Guidance for
Industry
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(https://www.fda.gov/media/70963/download)
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