Effect of system parameters on controlled release drug delivery
1. EFFECT OF SYSTEM PARAMETERS ON CONTROLLED
RELEASE DRUG DELIVERY
PRESENTED BY :
GANDHI SONAM MUKESHCHANDRA
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2. The system parameters are
1. Polymer solubility (Cp).
2. Solution solubility (Cs).
3. Partition coefficient (k).
4. Polymer diffusivity(Dp).
5. Solution diffusivity(Ds).
6. Thickness of polymer diffusional path(hp).
7. Thickness of hydrodynamic diffusion layer(hd).
8. Drug loading dose (A).
9. Surface area.
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3. 1. Polymer solubility (Cp)
• In the controlled release of a drug species from
either polymer membrane permeation controlled
(or) polymer diffusion controlled drug delivery
devices (or)other rate preprogrammed drug
delivery devices .
• To release at an appropriate rate drug require
adequate polymer solubility.
• The relationship
(Q/t) α Cp
• On the other hand
Q/t 1/2 α Cp 1/2
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5. • The difference in the solubility of steroid polymer can
range from 1 to 2 µg/ml to as high as 1152.8 µg/ml .
• Eg : addition of one or more hydroxyl groups to
positions 11, 17 and 21 on the progesterone skeleton.
progesterone skeleton
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7. • Eg: fillers are added to increase the polymer
solubility .
siliceous earth into silicone elastomers.
silicone
elastomer
siliaceous
earth
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8. 2.Solution solubility (Cs).
• Invivo sink condition should be maintained.
can be done by,
Concentration in the bulk should be zero.
By maintaining the solution concentration very
high than the bulk concentration by using a co-
solvent.
Cs >>Cb
Eg- ethynodiolacetate
The invitro release rates of steroids ,is greater in
the human plasma than the normal saline.
8
9. • Aqueous solubility of the drug varies significantly
similar to that of polymer solubility, dependent on the
upon the difference in the chemical structure ,types
and physicochemical nature .
Eg- esterification of testosterone reduces aqueous
solubility.
In the matrix type of drug delivery systems the effect of
solution solubility affects both the mechanism and rate
profiles of controlled drug release system.
The solubility can be increased by micelle formation
, complex formation ,cosolvency.
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10. 3.Partition coefficient(K).
• The partition coefficient of a drug for its interfacial
partitioning from the surface of a drug delivery device
towards an elution medium .
K=Cs/Cp
• Eg-in vitro studies of Norgestomet from silicon
capsules.
• The effect of partition coefficient on controlled release
of drugs from matrix type drug delivery device was
reported to be biphasic.
• Eg-ethynodiol diacetate.
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11. • The effect of alkyl chain length on the magnitude
of the partition coefficient is exponential.
Log Kn = log Ko – nπCH2
Eg-the solubility of alkyl-p amino benzoates.
• Addition of hydrophillic functional groups such as
-OH to as drug molecule tends to improve the
solution solubility.
LogKOH = logKp + nπOH
Eg-progesterone in silicone polymer.
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12. • The relationship between membrane
permeability Pm and partition coefficient K.
Pm=DpK
Eg-transdermal permeation of steroid.
• Variation in the cosolvency also has an effect
on partition coefficient.
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13. 4.Polymer diffusivity(Dp).
• The diffusion of small molecules in a polymer
structure is an energy activated process in which
the diffusant molecules move to equilibrium
positions when a sufficient amount of energy,
called energy of diffusion.
• Arrhenius relationship.
Dp=Doe-(Ed/RT)
D0=temperature independent frequency factor
Ed=energy of activation for polymer diffusion
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14. The molecular motions that leads to this activated state
are
• The blending of polymer chains.
• The intermolecular repulsion and resistance from their
neighbouring polymer chains.
Ed=Eb + Er
Polymerchains Diffusant
molecule 14
15. • The polymer diffusivity of a diffusant molecule
must be inversely proportional to the cube roots
of its molecular weight.
• It is also dependent on the type of functional
group and their stereo-chemical position in the
diffusant.
Factors affecting
i. Cross linking.
ii. Effect of crystallinity.
iii. Effect of fillers.
iv. Determination of polymer diffusivity.
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16. a)Cross linking.
• Polymer diffusivity decreases as the cross linking of the
polymer increase.
Eg-ethylene glycol dimethyl acrylate.
Dp =DЄ/ѳ
Where D-Intrinsic diffusivity of diffusant molecule.
b)Effect of crystallinity.
The crystallinity act similar to the cross linking agent.
Low density polyethylene has a low degree of
crystallinity than does high density polyethylene.
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17. c)Effect of fillers.
Fillers are often incorporated into a polymer to enhance its mechanical
strength.
Eg-finely ground silica.
d)Determination of polymer diffusivity.
Dp=h2p/6t1
t1-time axis intercept of the extrapolation through the steady state
drug release data.
The polymer diffusivity in an aged device can be determined from the
Dp=h2p/3tb
tb-negative time axis intercept of the extrapolation through the steady
state release data.
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19. Elastomeric polymers often contain very pure
and finely ground filler particles.polymer
diffusivity can be determined by
If the filler is inert adds only toruosity factor to
the diffusion process.
If the filler is active and it has the constant
absorption capacity.
If the filler is active its adsorption capacity is
directly proportional to the local
concentration of the diffusant molecules.
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20. REFERENCES.
1.Novel drug delivery system by………………………………………….Y.W.Chein.
2.Sustained controlled release drug delivery systems by…….Robinson J.R.
3.www.images.google.com
4.www.wickipedia.com
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