Biopharmaceutics Classification System

<h2 id="classes">Classes</h2>

<p>According to the Biopharmaceutics Classification System (BCS) drug substances are classified to four classes upon their solubility and permeability:<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a>
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<ul><li>Class I – high <a href="/facts/Intestinal_permeability/zQThl74p">permeability</a>, high <a href="/facts/Solubility/kLE9h3Jb">solubility</a> 
<ul><li>Example: <a href="/facts/Metoprolol/NmG0B0gn">metoprolol</a>, <a href="/facts/Paracetamol/SNDfQWcf">paracetamol</a><a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a></li>
<li>Those compounds are well absorbed and their absorption rate is usually higher than excretion.</li></ul></li>
<li>Class II – high permeability, low solubility
<ul><li>Example: <a href="/facts/Glibenclamide/4o1WPl5h">glibenclamide</a>, <a href="/facts/Bicalutamide/GVPLWejY">bicalutamide</a>, <a href="/facts/Ezetimibe/PWzKxomU">ezetimibe</a>, <a href="/facts/Aceclofenac/RUqTAt4v">aceclofenac</a></li>
<li>The <a href="/facts/Bioavailability/9l6na9MV">bioavailability</a> of those products is limited by their solvation rate. A correlation between the <i><a href="/facts/In_vivo/kWcWyl6f">in vivo</a></i> bioavailability and the <i><a href="/facts/In_vitro/evp3hAX6">in vitro</a></i> solvation can be found.</li></ul></li>
<li>Class III – low permeability, high solubility 
<ul><li>Example: <a href="/facts/Cimetidine/MX2vzIVg">cimetidine</a></li>
<li>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.</li></ul></li>
<li>Class IV – low permeability, low solubility 
<ul><li>Example: <a href="/facts/Bifonazole/GoRjU3vU">bifonazole</a></li>
<li>Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected.</li></ul></li></ul>
<h2 id="definitions">Definitions</h2>
<p>The drugs are classified in BCS on the basis of solubility and permeability.
</p><p>Solubility class boundaries are based on the highest dose strength of an immediate release product. A drug is considered highly soluble when the highest dose strength is soluble in 250 ml or less of aqueous media over the pH range of 1 to 6.8. The volume estimate of 250 ml is derived from typical <a href="/facts/Bioequivalence/8jt6Fm3p">bioequivalence</a> study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water.
</p><p>Permeability class boundaries are based indirectly on the extent of absorption of a drug substance in humans and directly on the measurement of rates of mass transfer across human intestinal membrane. Alternatively non-human systems capable of predicting drug absorption in humans can be used (such as in-vitro culture methods).  A drug substance is considered highly permeable when the extent of absorption in humans is determined to be 85% or more of the administered dose based on a mass-balance determination or in comparison to an <a href="/facts/Intravenous/AwwuD3Nu">intravenous</a> dose.
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<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/ADME/fPpj3sEW">ADME</a>
<ul><li><a href="/facts/Partition_coefficient/D4aTlBal">Partition coefficient</a></li>
<li><a href="/facts/Bioavailability/9l6na9MV">Bioavailability</a></li>
<li><a href="/facts/Drug_metabolism/I5nQ28Ma">Drug metabolism</a></li>
<li><a href="/facts/First_pass_effect/jfDsbq7S">First pass effect</a></li></ul></li>
<li><a href="/facts/Polar_surface_area/1eezjB9Q">Polar surface area</a></li>
<li><a href="/facts/IVIVC/H1sMCkCE">IVIVC</a></li></ul>

<h2 id="further-reading">Further reading</h2>

<ul><li>Folkers G, van de Waterbeemd H, Lennernäs H, Artursson P, Mannhold R, Kubinyi H (2003). <a href="https://archive.org/details/drugbioavailabil0000unse"><i>Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry)</i></a>. Weinheim: Wiley-VCH. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 3-527-30438-X.</li>
<li>Amidon GL, Lennernäs H, Shah VP, Crison JR (March 1995). "A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability". <i>Pharm. Res</i>. 12 (3): 413–20. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7617530">7617530</a>.</li></ul>

<h2 id="external-links">External links</h2>
<ul><li><a href="https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm">BCS guidance</a> of the <a href="/facts/U.S._Food_and_Drug_Administration/rCEnh9WB">U.S. Food and Drug Administration</a></li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1"><p>Mehta M (2016). Biopharmaceutics Classification System (BCS): Development, Implementation, and Growth. Wiley. ISBN 978-1-118-47661-1. <a href="978-1-118-47661-1" target="_blank">978-1-118-47661-1</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li>
<li id="fn:2"><p>Mehta M (2016). Biopharmaceutics Classification System (BCS): Development, Implementation, and Growth. Wiley. ISBN 978-1-118-47661-1. <a href="978-1-118-47661-1" target="_blank">978-1-118-47661-1</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li>
<li id="fn:3"><p>"Draft agreement" (PDF). www.ema.europa.eu. 22 June 2017. Retrieved 2019-07-03. <a href="https://www.ema.europa.eu/documents/scientific-guideline/draft-paracetamol-oral-use-immediate-release-formulations-product-specific-bioequivalence-guidance_en.pdf" target="_blank">https://www.ema.europa.eu/documents/scientific-guideline/draft-paracetamol-oral-use-immediate-release-formulations-product-specific-bioequivalence-guidance_en.pdf</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li>
</ol>

Biopharmaceutics Classification System open-in-new

Biopharmaceutics Classification System