BIOPHARMACEUTICS (FAF3471)

ODD SEMESTER Acad.Yr. 2023/2024

PHYSICOCHEMICAL PROPERTIES OF THE DRUG

AFFECTING THE ABSORPTION
Adhyatmika
Laboratory of Physical Pharmacy
Department of Pharmaceutics – Faculty of Pharmacy
Universitas Gadjah Mada

Faculty of Pharmacy UGM, August, 2023

 01

Course Objectives

intro 1. To understand the biopharmaceutical aspects,

especially related to the physicochemical factors that
affect the absorption of drug molecules,

2. To understand the benefit of the physicochemical

factors to optimize the bioavailability of drug in the
systemic circulation through absorption.
01

02
 02
To focus on the permeability (*)

intro

01

taken from: lubrizolcdmo.com

02 Suarez, Maorrum, Hughes (2012)

 03

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.
Volpe, 2010
01 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
 04

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
 05

Factors affecting permeability

transport process happens here
intro
physicochemical properties

01

Brodin, Steffansen, and Nielsen (2010) anatomophysiological factors

02
 06

Primary resources of this course

intro

01

CHAPTER 15 CHAPTER 1 CHAPTER 2

02
 07
Factors related to bioavailability

in vitro in vivo in clinic

intro
polymorphism

stability

particle size, charge

dissolution, pH dissolution, pH

permeability permeability
01 kinetics, dynamics kinetics, dynamics

02
 08
Why physico-chemical properties study?

solubility à I.V. administration

intro
pH à per oral (gastric/intestinal)
Route of
solubility à buccal/sublingual
administration
particle size à intra nasal
pH, solubility à opthalmic
Physico-chemical
01 properties
dissolution, pH à
Pharmacodynamics
immediate, prolonged

osmotic pressure, dissolution

Toxicology/safety
à multi-drug release, OROS
02
 09
Rate-limiting steps in drug absorption

intro

01

02
Suarez, Maorrum, Hughes (2012)
 10
Ion-molecule equilibrium (HH eq.)

intro

!
[𝐴 ]
01
𝑝𝐻 = 𝑝𝐾𝑎 + log
[𝐻𝐴]
!
[𝐴 ]
𝑝𝐻 − 𝑝𝐾𝑎 = log
02
[𝐻𝐴]
 11
Particle size (and charge)

Noyes-Whitney equation
intro surface tension

Ostwald-Freundlich equation à Ostwald ripening

(+)? (-)?
01

02 Wu et al (2011)
 12

Partition coefficient

intro

Wolk et al (2014)

SR Rahman (2011)
01

02
 13
Metastable crystal transformation

intro
Triggers:
temperature, pH change

01

02
 14
Polymorphism, solvate

intro

01

Suarez, Maorrum, Hughes (2012)

02
 15
Chemical stability (*)

wA + xB à yC + xD
intro
!#$ !# ' !# ) !# +
v=− =− = =
" #% & #% ( #% * #%

01
v=𝑘 𝐴 𝑛 𝐵 𝑚

Order of reaction: zeroth, first, second.

Based on experiment:
Zeroth: C vs t; first: log C vs t; and second: 1/c vs t.
02
 16

Consideration in drug product design

intro

01

Suarez, Maorrum, Hughes (2012)

02
 17
Excipients to improve PC properties

intro

01

Suarez, Maorrum, Hughes (2012)

02
 18
Excipients to improve PC properties

intro

01

Suarez, Maorrum, Hughes (2012)

02
 Thank you for your attention J

intro

01

Please kindly share me your thought about my

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