BIOPHARMACEUTICS (FAF3471)

ODD SEMESTER Acad.Yr. 2022/2023

ANATOMO-PHYSIOLOGICAL FACTORS
AFFECTING DRUG ABSORPTION
Adhyatmika
Laboratory of Physical Pharmacy
Department of Pharmaceutics – Faculty of Pharmacy
Universitas Gadjah Mada

Faculty of Pharmacy UGM, September (5, 6, 8), 2022

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Course Objectives
intro

1. To understand the anatomical and physiological factors

that affect the absorption of drug molecules,

2. To understand the benefit of the anatomical and

physiological factors to optimize the bioavailability of
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drug in the systemic circulation.

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To focus on the permeability (*)
intro

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taken from: lubrizolcdmo.com

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Suarez, Maorrum, Hughes (2012)
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Permeability definitions
intro
Anita Nair (Merck Group presentation)
v is the ability of a drug to pass across biological membrane.
Di and Kerns, 2016

v is the velocity of passage of a drug through a biological lipid

membrane.
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Volpe, 2010
v is defined as the rate of drug accumulation in the receiver chamber
normalized for tissue surface area.
Dahan and Miller, 2012

v is equal to the diffusion coefficient of the drug through the

membrane times the membrane / aqueous partitioning of the drug
divided by the membrane thickness. 02
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The permeability formulas

intro
𝑚 J = flux (µg cm-2 h-1 or mol cm-2 min-1)
𝐽= m = mass of compound m (qumulative transport, Qt)
𝐴𝑡 A = cross sectional area, during time t

𝑑𝐶 D = diffusion coefficient, diffusivity

𝐽 = −𝐷 dC = concentration gradient or partitioning (mol L-1)
𝑑𝑥 dx = distance, membrane thickness (length) 01

R = gas constant, T = Absolute temperature

𝑅𝑇 η = viscosity of the solution
𝐷= N0 = Avogadro’s number (6.02 x 1023)
6π η 𝑁𝑜 𝑟𝐴 rA = radius of the spherical solute

P = permeability coefficient (unit?) (effective or apparent?)

𝐽 = 𝑃 Δ𝐶 ΔC = C0 – Ct (C0, assuming sink condition)
02
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Factors affecting permeability

intro
transport process happens here

physicochemical properties

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Brodin, Steffansen, and Nielsen (2010) anatomophysiological factors
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Primary resources of this course

intro

CHAPTER 4
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CHAPTER 14
CHAPTER 1, 5, 7

CHAPTER 11, 12 02
CHAPTER 3, 10, 11, 12
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Anatomical and physiological factors

intro
Organs: liver, lung, kidney, brain, etc.
Cells: muscle cell, immune cell, nervous cell, etc.
Organelles: nucleus, ribosome, membrane, cytoplasm, etc.
Elements: Water, carbohydrate, protein, salts, etc.

Structures (anatomy)
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Functions (physiology)

Human Body Nervous system: brain, nerve, spinal cord, sensors

Respiratory system: respiratory tract, lung, alveoli, blood
Immune system: macrophages, lymphocytes, thymus
Cardiovascular system: heart, blood, veins, arteries
Digestive system: GI tract, enzymes, bile, liver 02
Cognitive system: brain cells, nervous cells, sensors
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Drug absorption
intro

01

Does NOT need energy: Does NEED energy:

PASSIVE, DIFFUSION ACTIVE TRANSPORT 02
à concentration gradient à transporters
à carrier-mediated
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Membrane structure
intro

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ü phospholipid bilayer: phospholipids à polar head, non-polar tail

ü integral proteins: transmembrane (intrinsic) 02
ü peripheral proteins: one-side only (extrinsic)
ü transporters: ATP-binding cassettes, ATP for activation
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The Gastro-intestinal+ absorption

intro

oral cavity: buccal, sublingual

gastric absorption: stomach

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intestinal absorption

colon absorption

rectal absorption
02
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Absorption in the oral cavity

intro
Mechanical digestion

Enzymatic digestion
(saliva: amylase, lipase)

Low surface area,

low absorption
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02
Hua (2019)
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Gastric absorption
intro
IF

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Park, Ha, and Kim (2020)

Motility: Transition: Enzymes:

Gastric emptying Surface area pepsin,
+ 15-30 minutes Absorption gastric lipase
Volume: + 35-250 mL 02
Intrinsic factors for vitamin B12 absorption:
glycoprotein produced in fundus & body
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Intestinal absorption
intro
Rodriguez et al (2022)

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Enzymatic: Pancreas à
Trypsionogen à Trypsin
Bile salts emulsify lipase and lipid

Long duration (motility+length) 02

Super-wide area
First-pass metabolism
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Absorption in the colon

intro

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taken from: theory.labster.com

Vitamins absorption: Remember gastric Intrinsic Factor? Lower permeability

Efflux transporter P-gp ↑
Water (re)absorption, transition surface area, transition Influx transporter hPepT1 ↓
membrane and mucosal structure, transition length
(1.5 : 8 to small intestine) 02
BCS class I à > 70%
Home of 700+ types of bacteria, fungi, and microbes. BCS class III or IV à < 50%
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Rectal absorption
intro

Melo et al (2018)
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Absorbed by rectum blood vessels, directly to systemic circulation, avoiding first-
pass metabolism.

Absorption of many drugs, peptides, and low-molecular weight protein ↑.

Dissolution issue: rectum’s limited fluid volume. Uneven absorption throughout

rectal membrane. 02
Leakage and discharge during application à unpredictable outcome
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First-pass metabolism
intro

01

Drug gets metabolized in specific location before reaching the

systemic circulation. 02

Mainly happen in liver, but also in GI-tract and lungs à CYP450.

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Entero-hepatic circulation
intro
Chloramphenicol, aspirin, paracetamol,
diazepam, lorazepam, morphine,
metronidazole.

Absorbed à liver à conjugated to

glucuronic acid à excreted into bile à
intestine à free drug from bacterial
metabolism à reabsorption. 01
Lower dose for effective therapy from drug
molecules recycling.

Increase toxicity to the liver and/or

intestines.

Blocking by: killing gut bacteria, glucuronic

acid inhibition à need adjustment for other 02
Mertens et al (2017) medication (drug-drug interaction)
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GI-tract transporters
intro
Daniel and Zietek (2015)

01

Proctor et al (2015)

Ø Selective to functional groups, compound classes, etc.

Ø Exist on both sides: Apical and basolateral.
Ø Blocking, inhibiting, or enhancing may cause drug-drug interaction. 02
Ø Naturally expressed for transport of nutrients.
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Exploiting
biological properties intro
for DDS
Things to exploit:

v Difference of pH à targeted
absorption
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v The lymphatic capillary à
first pass effect avoidance

v Transport limitation: surface

area, residing time à
targeted absorption

v Metabolism (microbes and 02

enzymatic) à targeted
absorption
taken from: pharmacy180.com
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General DDS strategies: AP perspective

intro
prodrug, encapsulation limited surface area / retention time

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02
Azman et al (2022)
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The lymphatic capillaries

intro

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02
Trevaskis, Kaminskas, and Porter (2015)
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Non-GI tract absorption: Lungs

intro

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De Boer et al (2001)

q Thickness: 50-60 μm (trachea), 0.2 μm (alveoli).

dramatic cell types change: Goblet (mucus), cilia
(move out mucus), basal (differentiate into 02
epithelial cells) à alveolar epithelial cells (AEC)

q ß Surface area vs diameter of the tract

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Non-GI tract absorption: Blood brain barrier

intro

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Bickel et al (2001)

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Non-GI tract absorption: Blood CSF barrier

intro

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Bickel et al (2001)

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Thank you for your attention J
intro

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Please kindly share me your thought about my

session: http://ugm.id/mycourseevaluation 02