In this Lecture I have covered how the Drug is absorbed when it is administered orally, what is BCS classification system, Role of BCS and Importance of Biopharmaceutics Classification System. I have discussed how the Pharmakinetics process occur, what is Absorption, Distribution, Metabolism and Excretion.

1. Prepared By: Ali Aasam Khan
4th Professional
Pharm-D
CECOS University of IT&
EMERGING SCIENCES,
PESHAWAR
GIT ABSORPTION

2. GIT ABSORPTION
 Gastrointestinal Tract (GIT) absorption of drugs refers to the process by which orally administered drugs are
absorbed through the various segments of the digestive system, starting from the mouth and ending in the small
intestine. This absorption is an important step in the pharmacokinetics of drugs, determining the rate and extent of their
entry into the systemic circulation.

3. FACTORS AFFECTING DRUG ABSORPTION
Drug absorption is a pharmacokinetic parameter that refers to the way a drug is absorbed from a pharmaceutical formulation
into the bloodstream.
The following are the factors that can affect the absorption of drugs:
 Physicochemical properties (e.g. solubility)
 Drug formulation (e.g. tablets, capsules, solutions)
 Route of administration (e.g. oral, buccal, sublingual, rectal, parenteral, topical, or inhaled)
 Rate of gastric emptying
 Blood flow to the organ
 Disease State
The main pharmacokinetic parameters for absorption include:
 Absorption rate constant:
Absorption rate/amount of drug remaining to be absorbed
 Bioavailability:
Amount of drug absorbed / drug dose
 A drug must be solubilized to cross the semipermeable cell membranes to reach the systemic circulation. These biological
barriers exist to selectively allow or inhibit the passage of native and foreign particles through them.

4. FACTORS AFFECTING SYSTEMIC AVAILABILITY OF
DRUGS
The following are the factors that affect the systemic availability of drugs:
1.Bioavailability:
Bioavailability is about how much of a drug reaches our bloodstream, telling us how effective the drug
will be.
2.First-Pass Metabolism:
First-pass metabolism happens when a drug goes through the liver for the first time. It can
change the drug and affect how much of it reaches the bloodstream.
3.Drug Formulation:
Different forms of a drug, like pills or liquids, can impact how well the drug dissolves and gets into
our body, affecting its overall effectiveness.
4.Route of Administration:
How we take a drug matters. For example, injecting it directly into our veins ensures the full
amount enters the bloodstream, but if taken by mouth, not all may get absorbed.
5.Drug Interactions:
Interactions between drugs can change how they work together, affecting the amount of a drug
available in the body and its overall effectiveness.

5. After oral administration, the fate of a drug involves several key steps:
 Absorption: The drug moves from its site of administration into the bloodstream. Factors like route of administration,
formulation, and chemical properties influence the rate and extent of absorption
 Distribution: The drug moves from the absorption site to tissues around the body, such as brain tissue, fat, and muscle.
Factors like blood flow, lipophilicity, and molecular size influence this process
 Metabolism: The drug undergoes metabolic processes in the liver or gut wall, where it may be converted into metabolites
to facilitate elimination. This step is crucial for drug inactivation or activation and can impact efficacy and safety.
 Excretion: The drug is removed from the body through processes like renal excretion or bile excretion. Factors like renal
dysfunction, age, and pathologies can affect excretion rates
FATE OF DRUG AFTER ORALADMINISTRATION

6. TYPES OF TRANSPORT SYSTEM AFTER DRUG IS ORALLY
ABSORBED
There are different types of transport systems that carry the drug from the absorption site to the site of action, these are the
following:
1.Passive Diffusion:
The most common method is where drugs move from an area of higher concentration to a lower concentration across cell
membranes, allowing for absorption without the need for energy.
2.Active Transport:
It involves the use of energy (ATP) to move drugs against their concentration gradient, ensuring absorption against natural
diffusion tendencies.
3.Facilitated Diffusion:
Utilizes carrier proteins to assist in the movement of drugs across membranes, generally in the direction of the
concentration gradient.

7. 4- Endocytosis and Exocytosis:
Involves the engulfment (endocytosis) or expulsion (exocytosis) of drug molecules by cell
membranes, often used for larger molecules or particles.
5- Paracellular Transport:
Drugs move through the tight junctions between cells, allowing for passage between cells
rather than through them.
6- Transcellular Transport:
Drugs move directly through the cells, crossing both the apical and basolateral membranes.

8. ROLE OF FICK’S LAW OF DIFFUSION IN GIT ABSORPTION OF
DRUGS
The drug distributes rapidly into a large volume after entering the blood, the concentration of the drug in the
blood initially will be quite low concerning the concentration at the site of drug absorption.
The equation can also be written as,
J= P (CGI)
Where J=dQ/dt and P= DAK/h (because the diffusion coefficient, area, and degree of lipid solubility are constant for each
drug), drug concentration in the plasma, C p, is extremely small compared to the drug concentration in the gastrointestinal tract,
C G

9. BIOPHARMACEUTICS CLASSIFICATION SYSTEM
The Biopharmaceutics Classification System (BCS) is a scientific framework designed to classify drug substances based on
their solubility and permeability characteristics.
It was introduced to aid in the development and regulation of pharmaceutical products, particularly bioavailability and
bioequivalence.
BCS was proposed by Gordon L. Amidon and co-authors in the late 1990s.
The BCS classifies drugs into four categories based on their solubility and permeability
Class I: High solubility, high permeability
Class II: Low solubility, high permeability
Class III: High solubility, low permeability
Class IV: Low solubility, low permeability

10. Class I: High solubility, high permeability
 These drugs have good solubility, meaning they dissolve well in the gastrointestinal (GI) fluids, and have high
permeability, allowing for efficient absorption across the intestinal membranes. Drugs in this class typically exhibit
excellent bioavailability, as they are readily absorbed and reach systemic circulation in significant amounts.
 Example: Metoprolol and Paracetamol
Class II: Low solubility, high permeability
 These drugs have poor solubility in GI fluids but high permeability, indicating efficient absorption despite limited
solubility.
 Formulating drugs in this class can be challenging due to their low solubility. However, their high permeability allows for
absorption, and strategies such as particle size reduction or formulation with solubilizing agents may be employed to
enhance solubility and, consequently, bioavailability.
 Example: Glibenclamide, Bicalutamide, Ezetimibe, and Aceclofenac

11. Class III: High solubility, low permeability
 These drugs have good solubility but face challenges in permeating the intestinal membranes efficiently.
 Although these drugs dissolve well in GI fluids, their limited permeability can lead to reduced bioavailability. Strategies to
enhance permeability, such as prodrug design or the use of absorption enhancers, may be considered during formulation.
 Example: Cimetidine
Class IV: Low solubility, low permeability
 Drugs in this class have poor solubility and limited permeability, posing significant challenges for absorption.
 Class IV drugs often face the most difficulties in terms of formulation and bioavailability. Overcoming both solubility and
permeability issues may require innovative approaches, such as the use of nanotechnology or specialized delivery systems.
 Example: Bifonazole

12. IMPORTANCE OF BCS
 BCS is like a guide for making and approving medicines. It helps guess how well a drug will work, guides regulatory
decisions, aids in creating the right forms of drugs, and even simplifies the approval process for certain generic drugs.
 BCS helps pharmaceutical scientists optimize drug formulations for better therapeutic outcomes.
 The Biopharmaceutics Classification System (BCS) predicts drug performance based on solubility and permeability.
 Regulatory agencies like the FDA use BCS for evaluating generic drugs and granting biowaivers.
 Pharmaceutical scientists use BCS to design drug formulations for optimal bioavailability.
 Bio waivers can be granted for drugs in certain BCS categories, reducing the need for in vivo bioequivalence studies
 Biowaivers refer to the waiver of in vivo bioavailability and/or bioequivalence studies for product approval. These refer
to the studies or the requirements which are not required for the approval of the product from higher authorities such as
US FDA.

13. HANDERSON-HASSELBALCH EQUATION
Henderson-Hasselbalch equation is a mathematical expression used to describe the relationship between the pH, the pKa
(acid dissociation constant) of a weak acid, and the concentrations of its ionized (conjugate base) and unionized (acid)
forms.
For Weak Acid: pH = pKa + log ([A-]/[HA]).
For a weak base: pH = pKa + log ([B]/[BH+]).

14. FACTORS AFFECTING HANDERSON HASSELBALCH
EQUATION
 Hander Hasselbalch equation is affected by various factors, including the pKa of the drug, the pH of the GI tract, and
the presence of other substances that can influence the pH.
USES
 Henderson-Hasselbalch equation is crucial for predicting how well a drug dissolves in the GI tract, impacting its
bioavailability.
 Pharmacists and pharmaceutical scientists use this equation to optimize drug formulations for better absorption and
efficacy.
 It helps calculate the ratio of ionized to unionized forms of a drug in different pH environments like the stomach and
intestine
 The equation aids in determining the pH of solutions, understanding the acidity or basicity of molecules, and predicting
ionized vs. unionized fractions of molecules
 Understanding acid-base equilibria through this equation is vital for drug absorption, distribution, metabolism, and
excretion (ADME)
 The Henderson-Hasselbalch equation is a fundamental tool in pharmacy, pharmaceutical sciences, chemistry, biology, and
biochemistry

15. REFERENCES
1- GIT Transit and drug absorption. Available from: https://pubmed.ncbi.nlm.nih.gov/11853157/
Last Accessed: March 02, 2024
2- Drug Absorption. Available from: https://www.news-medical.net/health/What-is-Drug-Absorption.aspx
Last Accessed: March 02, 2024
3- BCS and Pharmacokinetic Parameters. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175306/
Last Accessed: March 02, 2024
4- GIT Absorption of Orally Administered Drugs. Available from: Chapter No # 8: Pharmacokinetics of Oral Absorption,
Applied Biopharmaceutics and Pharmacokinetics, Seventh Edition (Leon Shargel)