Pharmaceutics (Part I) – Spring 2004 Page 31

Prof. C. Thompson (SB 383; 243-4643; charles.thompson@umontana.edu

Dissolution Equations, Calculations and Relationships - A Brief Survey.

In 1897, Noyes and Whitney described the quantitative analysis that correlated the amount of time it took
to dissolve a drug from solid particles. The current version of the equation is slightly modified from the
original but remains based on a diffusion layer model of dissolution (Scheme 1) of drug from a particle
into a large excess bulk medium.

Noyes-Whitney Equation:

The rate of dissolution (dM/dt)….

dM = DS(CS-Cb)
dt h

where:

M = amount of drug (material) dissolved (usually mg or mmol)

t = time (seconds)
D = diffusion coefficient of the drug (cm2/s)
S = surface area (cm2)
H = thickness of the liquid film
Cs & Cb = concentrations of the drug at the surface of the particle (surface = Cs) and the bulk
medium (bulk medium = Cb)

Drug
Diffusion Layer Bulk Solution
Particle

Cs

Cb

Scheme 1. Dissolution of drug particles according to diffusion layer model.

Pharmaceutics (Part I) – Spring 2004 Page 32
Prof. C. Thompson (SB 383; 243-4643; charles.thompson@umontana.edu

Problem 1: Calculate the dissolution rate of a hydrophobic drug having the following physicochemical
characteristics:
surface area = 2.5 x 103 cm2
saturated solubility = 0.35 mg/mL (at room temperature)
diffusion coefficient = 1.75 x 10-7 cm2/s
thickness of diffusion layer = 1.25 µm
[Note: need to convert to cm, so 1 µm = 1 x 10-4 cm and 1.25 x 10-4 cm]
conc of drug in bulk = 2.1 x 10-4 mg/mL

dM = DS(CS-Cb)
dt h

dM = (1.75 x 10-7)(2.5 x 103)( 0.35 mg/mL - 2.1 x 10-4 mg/mL)

dt 1.25 x 10-4

dM = (1.75 x 10-7)(2.5 x 103)( 0.349 mg/mL)

dt 1.25 x 10-4

dM = (1.75 x 10-7)(2.5 x 103)( 0.35 mg/mL - 2.1 x 10-4 mg/mL)

dt 1.25 x 10-4

dM = 1.53 x 10-4 = 1.22 mg/sec

-4
dt 1.25 x 10

NOTE!!!! The concentration in bulk solution is generally much lower than the saturated solubility. See
for example above, (0.35mg/mL – 0.00021 mg/mL), and the Cb term can sometimes be ignored.

Problem 2: What would the rate of dissolution be in Problem 1 if the surface area was increased to 4.3 x
104 cm2?

Answer: 4.3 x 104 cm2 is a 17.2-fold increase over the prior surface area (2.5 x 103 cm2).
Therefore, multiply the rate 1.22 mg/sec x 17.2 = 21 mg/sec (approx). Or you can recalculate the rate by
substituting all the values into the equation.
Pharmaceutics (Part I) – Spring 2004 Page 33
Prof. C. Thompson (SB 383; 243-4643; charles.thompson@umontana.edu

Diffusion - Through a Membrane:

A membrane is defined as a physical barrier that separates two or more regions. For our purposes, we
consider a cell membrane that is composed of phospholipids and proteins. Absorption of drugs across the
stomach lining/mucosa and the blood/brain barrier are two representative examples and important for
understanding drug transport into the circulation and CNS, respectively. Skin is another great example of
a membrane for the entry of drugs. The transport of drug molecules through a non-porous membrane
occurs by diffusion. Transport through porous membranes occurs by diffusion and convection (not
covered here). Similar to dissolution, the diffusion equation is…

dM = DAK(C1-C2)
dt h

M = amount of drug (material) dissolved (usually mg or mmol)

t = time (seconds)
D = diffusion coefficient of the drug (cm2/s)
A = surface area of membrane (cm2)
K = oil/water partition coefficient
h = thickness of the liquid film
C1 - C2 = concentration gradient where C1 is the concentration of drug at donor side of membrane
and C2 is the concentration of drug in the membrane at receptor side.
Cd
C1

donor compartment receptor compartment

(high drug conc) (low drug conc)

Cr
C2

Scheme 2. Diffusion model for Fick’s Law.

However, C1 and C2 are not measured since these are values within the membrane. Typically, the gradient
is measured as Cd - Cr, representing the partition at each phase, namely Ko/w = C1/Cd and Ko/w = C2/Cr. The
Integrated Studies uses C1 and C2 where Cd and Cr should be used, but it doesn’t really matter for the
calculation so long as you know what the gradient is.

Notes: The rate of drug transport into diffusional system is predominantly dependent upon the magnitude
of the concentration gradient – the other parameters are constant.