This document discusses how various system parameters affect controlled release drug delivery. It outlines five key parameters: 1) Solution diffusivity, which decreases with increasing solute concentration due to higher viscosity; 2) Thickness of the polymer diffusional path, which increases over time in matrix systems; 3) Thickness of the hydrodynamic diffusion layer, which also varies with the square root of time; 4) Drug loading dose, which influences drug flux but not duration in reservoir systems; and 5) Surface area, where increasing area leads to higher release rates across all controlled delivery systems. The document provides theoretical frameworks and experimental examples for how each parameter influences drug release profiles.

1. EFFECT OF SYSTEM
PARAMETERS ON
CONTROLLED RELEASE
DRUG DELIVERY.
Done by :
Hamed Barzeh
1st year M.pharm
KCP

2. Introduction
The mechanistic analysis of controlled release drug
delivery system reveals that the systemic (physiochemical)
parameters play a varying degrees of rate limiting roles
in controlling the drug release from different types of
controlled release drug delivery device.
Some of them are-
1.Solution Diffusivity (DS)
2.Thickness of polymer Diffusional path (hP)
3.Thickness of hydrodynamic diffusion layer (hd)
4.Drug loading dose (A)
5.Surface Area.

3. 1. SOLUTION DIFFUSIVITY (Ds):
The diffusion of solute molecules in a solution medium may
be considered as a result of random motion of molecules. The
solution diffusion process can be discussed by void occupation
model & the theory of free volume.
DS= Do e -(En/RT)
Where,
DS = solution diffusivity
D0 = pre exponential factor
En= energy of activation for solution diffusion.

4. For a solute whose molar volume is greater than or equal to the molar
volume of water molecules, the diffusivity of the solute molecules in the
aqueous solution (at 250C) is inversely proportional to the cube root of molar
volume.
The molar volume of a solute molecule is an additive property of its
constituent atoms and functional groups.
When solution diffusivity of various chemical group was compared on the
basis of molar volume.
The relative rates found that,
Alkane>Alcohols>Amides>Acids>Aminoacids>Dicarboxylic acids.

5. The diffusivity of solute molecules in an aqueous solution
usually decreases as its concentration increase. This
reduction is frequently related to the increase in viscosity
that usually accompanies the increase in solution
concentration.
The effect of viscosity (μ) is related to solution
diffusivity (DS).
DS = w / μ
Where, w is proportional constant.

6. bueche’s void occupation model . drug molecule X jumps
from it’s own void to a new equilibrium position in the
adjacent void

7. Linear relationship between release flux Q/t1/2 of desoxycortisone
acetate from a matrix-type silicon device and ((2A – CP) CP )1/2 values

8. 2. THICKNESS OF POLYMER DIFFUSIONAL PATH (hP):
The controlled release of a drug species from polymer membrane
permeation & polymer matrix controlled drug delivery systems is
essentially governed by the same physiochemical principles as defined
by Fick’s law of diffusion.
The observed difference in their drug release patterns is a result of the
difference in the time dependence of the thickness of their polymer
diffusional path hP.

9. Cont:
For membrane permeation controls of reservoir type drug
delivery devices fabricated from non-biodegradable and
non swollen polymers such as silicon elastomer.
The hP value is constant throughout the time span.
On the other hand, in matrix type drug delivery systems
fabricated from non-biodegradable polymers the
thickness of the diffusional path in the polymer matrix as
defined by the depletion zone grows progressively in
proportion to the square root of time

10. In the matrix type drug delivery device fabricated from a
biodegradable polymer such as polylactide coglycoside
polymer, the hP versus t1/2 and hP/ t1/2 (A- Cp/2)-1/2 relationship is
too complicated by the concurrent degradation of polymer
matrix.
But in matrix type fabricated from non-
biodegradable hydrophilic polymers like hydroxy
ethylmethacrylate. These relationships should also be
followed after equilibrium hydration state is reached.

11. Linear relationship between the thickness of drug depletion zone
hP in a matrix type silicone device and the square root of time

12. 3. THICKNESS OF HYDRODYNAMIC DIFFUSION LAYER (hd):
The rate-limiting role of the hydrodynamic diffusion layer hd
in determining drug release profiles can be visualized by
considering that as a device is immersed in stationary position in
a solution, a stagnant layer is established on the intermediate
surface of the device. The effective thickness of this stagnant
layer is dependent on solution diffusivity (Ds) and varies with the
square root of times.
The diffusivity of the solute molecule in an aqueous
solution is usually decreases as its concentration increases. This
reduction is frequently related to the increase in solution
viscosity that usually accompanies the increase in solute
concentration.

13. S
Film boundary
bulk
solution
Stagnant layer
Cs
c
Diffusion layer model

14. Linear dependence of the in vitro release rate Q/t of megestrol
acetate silicon capsules on the reciprocal of wall thickness hm . .

15. 4. DRUG LOADING DOSE(A):
In the preparation of drug delivery device varying loading doses of
drug are incorporated in to the device as required for different
lengths of treatment.
Q= [(2A – CP) CP DPt]1/2
This equation indicates variation in the drug loading dose A in
matrix type drug delivery systems also affects the magnitude of the
drug delivery flux Q/t1/2.
Variation in drug loading doses was also found to influence the
drug release profiles from matrix type drug delivery devices.

16. On other hand, the rate of drug release from a membrane permeation
controlled reservoir type polymeric drug delivery device is
independent of the loading dose.
Q/t = C pKDdDm/KDdhm + Dmhd
Variation in loading doses result only in a change in the duration of
constant drug release profiles.
Ex.
The release rate of norgestrienone from silicon capsules with a
loading dose of 2.5mg/cm is essentially the same as that from capsules
with loading level of either 7.5 or 12.5mg/cm for a duration of 180 days,
after this period almost no steroids remains in the capsules

17. Linear dependence of Q/t1/2 on [2A – CP]1/2 :
(A) progesterone and (B) hydrocortisone

18. % of loading dose release vs time(hr)

19. 5. SURFACE AREA:
The dependence of the rate of drug release on the
surface area of drug device is well known
theoretically and experimentally.
As the surface area increases, the rate of drug release
increases in all types of controlled drug delivery
systems.
Ex.
Effect of surface area on the release rate of 1-(2-
chloroethyl)-3-(trans-4-methylcyclohexy)-1-nitrosourea
from silicon capsules.

20. Q/T(mg/day) vs Surface Area

21. References:

22. Thank you