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Mathematical Modeling of Diffusion Controlled Drug Release Profiles from

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International Journal of Research and Scientific Innovation (IJRSI) | Volume VI, Issue V, May 2019 | ISSN 2321–2705
Mathematical Modeling of Diffusion Controlled Drug
Release Profiles from Nanoparticles
Ibtihag Yahya1, Razan Atif1, Lina Ahmed1,Tahleel Salah Eldeen1, Akram Omara1, Megdi Eltayeb1*
1
Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum, Sudan
* Corresponding author. Dr. Megdi Eltayeb
Abstract:-This paper is mainly focused on the diffusion-control
mechanism, involved in the release process based on
mathematical modeling approaches that were collected from the
literature which was developed as novel method to estimate and
describe the drug release from matrix devices and simulations of
drug release from these matrix devices using MATLAB software
to conduct a comparison in order to study and differentiate the
effect of each factor on the drug release profile. The aim of this
paper was to establish models and to differentiate the kinetic
release behavior of drug models from polymeric nanoparticles.
Mathematical modeling of the release profiles was conducted,
showing that the reduction in the thickness of the device as 42, 35
and 20 × 10-9 m for C3, C2 and C1 respectively, when fixes the
diffusion coefficient value results in inversely proportion relation
as increase in the release rate due to the decreases in the
thickness values and in other hand when fixed the thickness
value and varying the diffusion coefficient as 0.63, 2.50 and 1.01
× 10-15 cm²/s for C4, C5 and C6 respectively, this results in directly
proportional relation as the release rate increasing due to the
increase in the diffusion coefficient. The simulation results
validated the use of the mathematical models’ equations in the
field of manufacturing drug delivery systems and facilities to
select an appropriate carrier system geometry for the drug and
help in the predetermining the drug release.
Keywords: Mathematical Modeling, Diffusion, release profiles,
nanoparticles
I. INTRODUCTION
C ontrolled drug release is based on diffusion through
polymer nanoparticles, swell or erosion of polymers
through different characteristics such as ion exchange and
osmotic effects and various other phenomena[1-3]. Further,
when designing controlled-release systems, the identification
and understanding of the specific mechanisms and the
intricate in the release process and the distinction between
them and the understanding of their respective characteristics,
is more important than the understanding of one mechanism
contributory in a given time in the drug delivery and the
medication administration process [4, 5]. The most frequent
design to acquire a controlled drug release is by establishing a
drug in a polymer nanoparticles matrix. Thus, the polymer
that is used for this purpose can be a hydrophilic or a
hydrophobic matrix based on the nature of the drug that can
be closed or submerged in hydrogel and be compatible with
varied and different mechanisms of the drug delivery
controlled release systems [6-8].
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Recently, controlled release drug delivery has become the
principles and standards in the modern pharmaceutical design.
On the positives side, dense and extensive research has been
undertaken in accomplishing much better drug product
reliability, effectiveness and safety. In this paper, the
mathematical equations of the controlled release systems are
presented and simulated. Furthermore, there are several
modeling approaches in the literature[9, 10]; those that are
relevant to this work and which were used to simulate the
drug release behavior from these matrix devices are described
in method section. The system geometry in the matrix devices
greatly affects the drug profile, the resulting profile equations
of the release were described in three different techniques
using an analytical solution to disseminate the unsteady-state
drug in a one-dimensional slapping matrix which was
described by the second Fick’s diffusion law [11-13]. A
model has been developed as mentioned in the study [14],
where this model is considered that both polymer relaxation
and drug diffusion are key factors in drug release and also,
this model represents partial absorption of the solvent (or
release of the solvent) that have been normalized in relation to
equilibrium conditions.
One of the most applicable mechanisms for the drug release is
the diffusion-control mechanism, which is characterized by
the release of the drug to be diffused through a membrane
acting as a barrier and is dispersed uniformly in non-
degradable matrix which means it’s not soluble in water. In
brief, the diffusion mechanism through the polymer
nanoparticles occurs when the drug or active agent passes
through the polymer nanoparticles matrix, which acts as a
controlled release device, since the release rate of the drug
decreases with the continuation of the release, this happen
when the active agent has a longer travel distance. Therefore,
requires more time to released [15, 16]. In view of basic types
of diffusion devices, there are two types the “Reservoir
diffusion system” and “Matrix diffusion system”. The matrix
system type of diffusion device which it’s alsohave two types
of "Monolithic Devices" where the monolithic means that
something is big and made of one thing and these devices are
used for estimating the drug diffusion coefficient in the
membrane known as monolithic solutions and monolithic
dispersions as presented by Siepmann andSiepmann[9], with
common geometries that involved in many pharmaceutical
dosages forms which follows homogeneous diffusions to help
in determine the diffusion of drugs using the available theories
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International Journal of Research and Scientific Innovation (IJRSI) | Volume VI, Issue V, May 2019 | ISSN 2321–2705

and in this study, we will focus on the monolithic solutions = (5)

matrix system device where the ratio of the initial drug ²
loading less than the drug solubility drug that is dispersed or 1− ² ²
𝑒𝑥𝑝 ×
²
dissolved in the release controlling matrix.
( )² ²
( )²
𝑒𝑥𝑝
²
II. METHOD
Used MATLAB software to apply the equations below in Where p is the dummy variable,qnis the root of the Bessel
order to simulate the release behavior from the matrix particle function of the first kind of zero order, R is the cylinder radius
and display the release curves for each equation where and H is the cylinder height.
mathematical models and numerical simulation techniques III. RESULT
play a major role in understanding and choosing the optimal
and most suitable design of the drug delivery devices and the Describe the releases of the drug is very complex, such as that
drug release rate. used in polymer nanoparticlescarrier-based drug delivery
systems. Here we discuss results for drug release via diffusion
The diffusion process is the most important process in the for three different geometries such as the slab, spherical and
drug release and when describing the process, the Fick’s law cylindrical geometries and to simulate the diffusion control
is considered as best equation for that specifically, for the system mechanism for the polymer nanoparticles.
matrix system that has a uniformly distributed drug
Table 1: The Formulation data that wants to test the release rate from the
throughout the polymer nanoparticles matrix, a one- pharmacokinetic matrix particle with different geometries slab, Spherical and
dimensional slap-shaped matrix drug diffusion can be Cylinders Devices via diffusion-control mechanism.
described by Fick’s second law of diffusion in unsteady-state.
Slab Spherical Cylinders Device
which was considered in two cases [17, 18]: Device Device
1. when the drug diffusion coefficient is assumed to be Formulation Diffusion Thickness Radius Radius Height
Coefficient (× 10-9 m) (nm) (nm) (nm)
constant: (× 10-15
= (1) cm²/s)
C1 1.28 20 25 30.5 63
2. when the diffusivity is concentration-dependent: C2 1.28 35 32.5 25 63
C3 1.28 42 40.5 18 63
= 𝐷(𝐶 ) (2) 0.63 30.5 40.5 80.5
C4 22
C5 2.50 22 30.5 40.5 80.5
Where the D is the drug diffusion coefficient, C is the drug C6 1.01 22 30.5 40.5 80.5
concentration. The drug release profile is affected C7 1.79 - - 45 10
substantially by the system geometry in the matrix devices C8 1.79 - - 45 45
and here is an analytical solution of the eq. (1) for the C9 1.79 - - 45 180
resulting release profile equations in three different techniques
[11]: We have chosen the mathematical models that was proposed
for matrix diffusion which mentioned above whether the drug
1) Slabs with flat surfaces delivery device: release kinetics depend fundamentally on the diffusion
( )² ² coefficient, thickness, radius and height of the delivery device
=1− ² ( )²
𝑒𝑥𝑝 (3) the data values of their parameter was listed in (.
²

Where M is the absolute cumulative amount of drug released Table 1), Eq.(3) was used to the simulation of the diffusion
at time t, Mois the initial amount of drug in the device, n is the polymer nanoparticles mechanism with slab geometry,where
dummy variable and L is the thickness of the film. have conducted a comparison between the data that presented
2) Spherical delivery device: in (.
²
=1− 𝑒𝑥𝑝 (4) Table 1) in order to evaluate the effect of both diffusion
² ² coefficient and thickness parameters when keeping one
Where R is the sphere radius parameter constant and varying the another.

3) Cylinders delivery device: We see that a reduction in the thickness of the device as (42,
35 and 20) × 10-9 m for C3, C2 and C1 respectively, when fixes
the diffusion coefficient value results in inversely proportion
relation as increase in the release rate due to the decreases in
the thickness values as shown in ( Fig1).

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International Journal of Research and Scientific Innovation (IJRSI) | Volume VI, Issue V, May 2019 | ISSN 2321–2705
Fig1:: The diffusion kinetics of three different particles C1, C2 and C3 with
different value of thickness L for slab geometry, each color represents the
effect of the thickness on the release kinetics.
In other hand when fixed the thickness value and varying the
diffusion coefficient as (0.63, 2.50 and 1.01) × 10-15 cm²/s for
C4, C5 and C6 respectively, this resultsin
in directly proportional
relation as the release rate increasing due to the increase in the
diffusion coefficient as shown in (Fig2).
Fig2:: The diffusion kinetics of three different particles C4, C5 and C6 with
different value of diffusion coefficient D for slab geometry, each color
represents the effect of the diffusion coefficient on the release kinetics.
In addition, when computing thee drug release profiles from
the spherical devices as diffusion-controlled
controlled drug release
which was simulated using Eq. (4) for the spherical devices
monolithic solutions matrix system when keeping the
diffusion coefficient constant at 1.28 × 10-15 cm²/s and
varying the radius as (30.5, 25 and 18 nm), resulted in
inversely proportion relation as the drug release rate increases
with decreasing device radius as illustrated in ((Fig3).
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23
Fig3:: The diffusion kinetics of three different particles C1, C2 and C3 with
different value of radius R for spherical geometry, each color represents the
effect of the radius on the release kinetics.
kinetic
In the case of keeping the radius value constant at 30.5 nm
and varying the diffusion coefficient as (0.63, 2.50 and 1.01)×
1.01)
10-15 cm²/s for C4, C5 and C6 respectively, and when compared
the results of this formulation can clearly found ac directly
proportional relation as the release rate increases as the
diffusion coefficient increase as shown in (Fig4).
Fig4:: The diffusion kinetics of three different particles C4, C5 and C6 with
different value of diffusion coefficient D, for spherical geometry, each color
represents the effect of the diffusion coefficient on the release kinetics.
The computed release profiles of diffusion mechanism with
cylindrical geometry as a function of time when varying the
radius was simulated using Eq. (5) and the result was
presented in (Fig5).
). It can be seen that a reduction in radius
values as (30.5,
30.5, 25 and 18) nm for C1, C2 and C3 respectively.
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International Journal of Research and Scientific Innovation (IJRSI) | Volume VI, Issue V, May 2019 | ISSN 2321–2705
23

Fig5:: The diffusion kinetics of three different particles C1, C2 and C3 with Fig7: The diffusion kinetics of three different
rent particles C7, C8 and C9 with
different value of radius R for cylindrical geometry, each color represents the different value of height H for cylindrical geometry, each color represents the
effect of the radius on the release kinetics. effect of the height on the release kinetics.

Fixes
ixes the other parameters resulted in increasing the release IV. CONCLUSION
rate but when varying the diffusion coefficient as (0.63, 2.50
In the context of this study, we successfully completed the
and 1.01) × 10-15 cm2/s for C4, C5 and C6 respectively, and
simulation of the mathematical models for drug delivery
keeping the other factors constant that were resulting in
mechanisms for controlled release and discussed in a clear
directly proportional relation as the release rate increases as
manner the effect of multiple parameters on the release rate
the diffusion coefficient increase as shown in ((Fig6).
where this paper focused on the release mechanisms for the
drug delivery systems via diffusion-controlled.
diffusion It also
presented the basic expressions for the different mechanisms
of the drug delivery-controlled release systems in slab,
spherical and cylindrical geometries based on the
mathematical models’ equations that were extracted from the
previous studies
udies and we have focused on those equations that
were related to this work. The simulation results validated the
use of the mathematical models’ equations in the field of
manufacturing drug delivery systems and facilities to select an
appropriate carrier system geometry for the drug and help in
the predetermining the drug release.
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