RATE CONTROLLED Dds by jig.pptx m pharm 2nd sem .

1
RATE CONTROLLED DRUG
DELIVERY SYSTEM
Presented by : JIGNASA PARMAR

2 CONTENT
 Introduction
 Classification of rate controlled DD system
 Rate pre-programmed DD system
 Polymer membrane permeation controlled drug delivery system
 Polymer matrix diffusion controlled drug delivery system
 Micro reservoir partition controlled drug delivery system
 Activation modulated DD system

3 Introduction
 Controlled drug delivery is one which delivers the drug at a predetermined
rate, for locally or systemically, for a specified period of time.
 These systems are capable of controlling the rate of drug delivery, sustaining
the duration of therapeutic efficacy, and/or targeting the delivery of drug to
a tissue.
 These are able to specify the release rate and duration in vivo precisely, on
the basis of simple in vitro tests.
 Controlled release is perfectly zero order release that is the drug release
over time irrespective of concentration.

5 Objectives of Rate controlled drug delivery system
 The chief objective of most products should be controlled delivery to reduce
dosing frequency, to an extend that once daily does is sufficient for
therapeutic management though a uniform plasma concentration at a
steady state.
 The major objectives includes:
 Predict drug release rated from and drug diffusion behavior through out
the polymer, thus avoiding excessive experimentation.
 Desing new drug delivery system based on general release expressions.
 Optimize the release kinetics.

6 Advantages of CR DDS
Clinical advantages:
Reduction in frequency of drug administration
Improved patient compliance
Reduction in drug level fluctuation in blood
Reduction in total drug usage when compared with conventional
therapy
Reduction in drug toxicity
Stabilization of medical condition (because of uniform drug level)
Economical to healthcare provider and the patient

7 Advantages of CR DDS
 Commercial / industrial :
 technological leadership
Product life-cycle extension
Product differentiation
Market expansion
Patent extension

8 Disadvantages of CR DDS
 Delay in onset of drug action
 Possibility of dose dumping in a case of poor formulation strategy
 Increased potential for first pass metabolism
 Greater dependance on GI residence time of dosage form
 Possibility of less accurate dose adjustment in some cases
 Cost per unit dose in higher when compared with conventional doses
 Not all drugs are suitable for formulating into ER dosage form

9 Classification of CRDDS
Rate pre-programmed drug delivery system
Activated modulated drug delivery system
Feedback regulated drug delivery system
Site targeting drug delivery system

10 1. Rate pre-programmed DDS
 In this, the release of drug molecule from the delivery system is pre-planned
with particular flow rate profile of medicine.
 The system controls the molecular of drug molecules in or across the barrier
medium within or surrounding the delivery system.
 Types:
a) Polymer membrane permeation controlled system
b) Polymer matrix diffusion-controlled system
c) Micro reservoir partition controlled system

11 a) Polymer membrane permeation controlled system
 In these system, the drug is completely or partially encapsulated in a drug reservoir cubical
whose drug releasing surface is covered by flow rate controlling polymeric membrane.
 In drug reservoir, the drug can be solid or dispersion of solid drug particle or concentrated
drug solution in a liquid or in a solid type dispersion medium.
 The polymeric membrane may be made-up of the fabricated form of homogeneous or
heterogeneous non- porous or partial microporous or semipermeable membrane.
 Release of drug molecules is controlled by:
• Partition coefficient of the drug molecule.
• Diffusivity of the drug molecule.
• The thickness of the rate controlling membrane.

12  The drug reservoir is a
suspension of progesterone &
barium sulphate in silicone
medical fluid .
 It is encapsulated in vertical
limb of T – shaped device
walled by a non- porous
membrane of ethylene-vinyl
co- polymer.
 It is designed to deliver
natural progesterone
continuously in uterine cavity
at a daily dosage rate of at
least 65 day to achieve
contraception for 1 year.
Ex: Progestasert
IUD

13 b) Polymer matrix diffusion controlled DDS
 In this type, drug reservoir is prepared by homogeneously dispersing drug
particle in rate controlling polymer matrix from either a lipophilic or
hydrophilic polymer.
 The drug dispersion in the polymer matrix is accomplished by either,
1) Blending therapeutic dose of drug with polymer or highly viscous base
polymer, followed by cross linking of polymer chains
2) Mixing drug solid with rubbery polymer at elevated temp.

14 Ex: nitro-Dur
 Nitro- dur is a transdermal
system contain nitroglycerin in
acrylic based polymer adhesive
with a resinous cross linking
agent to provide a continuous
source of active ingredient.
 It is designed for application on
intact skin for 24hrs to provide a
continuous transdermal infusion
of nitroglycerin at dosage rate of
0.5mg/cm2/day for the
treatment of angina pectoris.

15
3) Micro reservoir partition controlled drug delivery system
 In this type , drug reservoir is fabricated by micro dispersion of an aqueous
suspension of drug in biocompatible polymer to form homogenous
dispersion.
 Depending upon the physicochemical properties of drug & desired rate of
drug release, the device can be further coated with a layer of biocompatible
polymer to modify the mechanism & the rate of drug release.
 Release of drug molecules is controlled by;
 Partition coefficient
 Diffusivity of drug
 Solubility of drug

16
Ex. Syncro mate -C
 It is fabricated by drug reservoir, which is a
suspension of norgestomet in an aqueous
solution of PEG 400, in a viscous mixture
of silicone elastomer
 After adding the catalyst, the suspension
will be delivered into the silicon medical
grad tubing ,which serves as mold as well
as the coating membrane & then
polymerized in situ.
 The polymerized drug polymer
composition is the cut into cylindrical drug
delivery device with the open ends.
 It is designed to be inserted into the
subcutaneous tissue of the livestock’s ear
flap & to release norgestomet for up to 20
days for control estrus & ovulation as well
as for up to 160 days for growth
promotion.

17 Activation modulated drug delivery system
In this group of controlled release
drug delivery system, the release of
drug molecules from the delivery
system is activated by some
physical, chemical, or biochemical
process and/ or by energy supplied
externally.

18
 Based on nature of the process or type of energy used they can be classified into
1) Physical means:
a) Osmotic pressure activated DDS
b) Hydro dynamic pressure activated DDS
c) Vapor pressure activated DDS
d) Mechanically activated DDS
e) Magnetically activated DDS
f) Sonophoresis activated DDS
g) Iontophoresis activated DDS
h) Hydration activated DDS
i) Laser activated DDS

2) Chemical means:
a) pH activated DDS
b) Ion activated DDS
c) Hydrolysis activated DDS
d) Chelation activated DDS
3) Bio chemical means:
a) Enzyme activated DDS
b) Biochemical activated DDS
c) Antigen activated DDS
d) Antibody activated DDA
19

20 a) Hydrodynamic pressure activated DDS
Also called as push- pull osmotic
pump.
This system is fabricated by
enclosing a collapsible,
impermeable container, which
contains liquid drug formulation
to form a drug reservoir
compartment in side rigid shape
– retaining housing.
A composite laminate of an
adsorbent layer and a swellable,
hydrophilic polymer layer is
sandwiched.

Rate controlling factors:
 Fluid permeability
 Effective surface area of the wall with the annular
opening.
 Hydrodynamic pressure gradient.
21

22 b) Vapor pressure activated DDS
In this system, the drug reservoir in a solution
formulation, is contained inside an infuscate
chamber.
It is physically separated from the vapor
pressure chamber by a freely movable bellows.
The vapor chamber contains a vaporizable
fluid, which vaporizes at body temp. & creates a
vapor pressure.
Under the vapor pressure created, the bellows
moves upward & forces the drug solution in the
infuscate chamber to release, through a series to
flow regulators & delivery cannula into the blood
circulation at a constant flow rate.

23
 Rate controlling factors:
 Differential vapor pressure
 Formulation viscosity
 Size of the delivery cannula
For ex: An implantable infusion pump for the constant infusion of
heparin for anti- coagulant therapy, insulin in diabetic treatment &
morphine for patient suffering from the intensive pain of terminal
cancer.

24 c) Magnetically active DDS
In this type, drug reservoir is a dispersion of
peptide or protein powders in polymer matrix
from which macromolecular drug can be
delivered only at a relatively slow rate.
This low rate of delivery can be improved by
incorporating electromagnetically triggered
vibration mechanism into polymeric device
combined with a hemispherical design.
Device is fabricated by positioning a tiny
magnate ring in core of hemispherical drug
dispersing poly matrix.
The external surface is coated with drug
impermeable polymer (ethyl vinyl acetate or
silicon elastomer) except on cavity at the center
of the flat surface.

25  This delivery device is used to deliver protein drugs such as
bovine serum albumin, at a low basal rate, by a simple diffusion
process under non triggering condition.
 As the magnet is activated to vibrate by external electromagnetic
filed, drug molecules are delivered at much higher rate

26 d) Sonophoresis activated DDS
 Also called as phonophoresis.
 This type of system utilizes
ultrasonic to activate or
trigger the delivery of drug
from polymeric drug delivery
device.
 System can be fabricated from
nondegradable polymer
(ethylene vinyl acetate) or
bioerodiable polymer.
 The potential application of
sonophoresis to regulate the
delivery of drug was recently
reviewed.

27 e) Iontophoresis activated DDS
 This type of system uses electrical current to activate & to modulate the diffusion of
charged drug across biological membrane.
 Iontophoresis – facilitated skin permeation rate of charged molecule (i) consist of 3
components & is expressed by,
Where,
Jp =passive skin permeation flux
= KsDs. dC/hs
Ks = partition coefficient for interfacial partitioning from donor solution to stratum corneum
Ds = diffusivity across the skin
dC/hs = concentration gradient across the skin

28
 = electrical current driven permeation flux
=
= electric valency of the ionic species i
= diffusivity of ionic species I in the skin
F = faraday constant
T= absolute temperature
donor conc. of ionic species I in the skin
= electrical potential gradient across the skin
 Jc(convective flow driven skin permeation flux)
= k Cs Id
Where,
K = proportionality
constant
Cs= conc. In the skin tissue
Id= current density applied

29 g) Ion- activated DDS
An ionic or a charged drug can be
delivered by this method & this
system are prepared by first
complexing an ionic drug with an
ion-exchange resin containing a
suitable counter ion.
Ex. By forming a complex between
a cationic drug with a resin having a
So3- group or between an anionic
drug with a resin having a N(CH3)3
group.
The granules of drug-resin complex
are first treated with an
impregnating agent &then coated
with a water-insoluble but water-
permeable polymeric membrane.

30
 This Membrane Serves As A rate- Controlling Barrier To
Modulate The Influx Of Ions As well as the release of drug
from the system
 in an electrolyte medium, such as gastric fluid ions diffuse
into the system react with drug resin complex & trigger the
release of ionic drug.
 Since the GI fluid regularly maintains a relatively constant
level of ions, theoretically the delivery of drug from this ion
activated oral drug delivery system can be maintained at a
relatively constant rate.

31
h) Hydrolysis- activated DDS
 This type of system depends on the hydrolysis process to activate the release
of drug.
 Drug reservoir is either encapsulated in microcapsules or homogeneously
dispersed in microspheres or nano particles for injection.
 It can also be fabricated as an implantable device.
 All these system prepared from bioerodiable or biodegradable
polymer( polyanhydride, polyoethoesters).
 It is activated by hydrolysis – induced degradation of polymer chain & is
controlled by rate polymer degradation
 LHRH- releasing biodegradable subdermal implant, which is designed to
deliver goserelin, synthetic LHRH analog for once a month treatment of
prostate carcinoma.

RATE CONTROLLED Dds by jig.pptx m pharm 2nd sem .

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