Description about a type of activation modulated drug delivery system, which a type of control drug delivery system. Also, give a detailed description about each subclassification. CrDDS is one which delivers the drug at a predetermined rate, for locally or systematically, for a prolong period of time.

1. ACTIVATION MODULATED
DRUG DELIVERY SYTEM
Presented by: Under the guidance of:
Sonal Mehrotra Dr. Srinivas Mutalik
M.Pharm , Part-1, HOD, Pharmaceutics
Dept. of Pharmaceutics MCOPS, Manipal
MCOPS, Manipal

2. CONTENTS:-
Theme Question-01
Theme Question-02
Introduction
Classification
Various physical activated system
Various chemical activated system
Various biochemical activated system
References
2

3. THEME QUESTION -01
What is DRUG DELIVERY
SYSTEM?
3

4. THEME QUESTION- 02
What is CONTROLLED DRUG
DELIVERY SYSTEM?
4

5. INTRODUCTION
• Type of controlled release dosage form
• Definition:-
DDS is activated by:-
 Physical process
 Chemical process
 Biochemical process
And facilitated by the energy supplied externally.
• The rate of drug release is then controlled, based on the nature
of the process applied or the type of energy used.
5

6. CLASSIFICATION
Activation
modulated
DDS
Physical
Means
1. Osmotic pressure activated
Ex: Acutrium Tab (PPA HCl)
2. Hydrodynamic pressure activated
3. Vapor presure activated
Ex: Infusaid pump (Heparin)
4. Mechanically activated
Ex: M.D. Nebulizer ( Buserelin)
5. Magnetically activated
Ex: Hemisphere (bovine serum albumin)
6. Sonophoresis
7. Iontophoresis activated
Ex: Phoresor by Motion Control
8.Hydration activated
Ex: Valrelease Tab (Valium)
Chemical
Means
1. pH-
activated
2. Ion-
activated
3. Hydrolysis
activated
Biochemical
Means
1. Enzyme-
activated
Ex: Albumin
microsphere (5-
Fluorouracil)
6

7. Physical Means:-
7

8. Osmotic pressure-activated DDS:
• This type of activation-controlled delivery system depends on
osmotic pressure to activate the release of drug. To release in
solution form at a constant stem
• The drug reservoir -A solution
-A solid formulation
• Contained within a semipermeable housing with a controlled
water permeability.
• The drug in solution form, released through a special laser-
drilled delivery orifice.
• Constant rate of drug release is under controlled gradient of
osmotic pressure.
• Examples:- Alzet osmotic pump [IMPLANTABLE]
Acutrim tablet [ORAL RATE CONTROLLED DDS]
8

9. Schematic representation of the basic
model of osmotic pressure-activated
DDS
Where, vs is volume of osmotic agent compartment
vd is volume of drug compartment
9

10. •For DDS containing a solution
formulation, the intrinsic rate
of drug release Q/t is defined
by:
For DDS containing a solid
formulation, the intrinsic rate of
drug release Q/t is defined by:
Where, Pw, Am & hm are the water permeability, effective
surface area & thickness of the semipermeable housing,
respectively; (πs-πe) is differential osmotic pressure between
the drug delivery system & environment & Sd is the aqueous
solubility of drug contained solid formulation
)( es
hm
PwAm
t
Q
  Sdes
hm
PwAm
t
Q
)(  
10

11. • The release of drug molecule from this type of delivery system
is activated by osmotic pressure and controlled at a rate
determined by:-
1) The water permeability
2) The effective surface area of the semipermeable membrane
3) Osmotic pressure gradient
• Representative of this type of delivery systems are as
follows:
11

12. Example: Alzet Osmotic Pump
Implantable or insertable CrDDS.
Alzet Pumps have 3 osmotic layer:-
• Rate-controlling, semipermeable membrane
• Osmotic layer
• Impermeable drug reservoir
The drug reservoir is contained within a collapsible,
impermeaable polyester bag.
Principle of Operation:-
ALZET pumps works by osmotic displacement.
 Water enters the pump across the outer, semi-
permeable membrane due to the presence of a high
osmotic chamber.
The entry of water causes the osmotic chamber to
expand, thereby compressing the flexible reservoir.
Delivering the drug solution through the delivery
portal.
12

13. Hydrodynamic Pressure- activated DDS:
• A drug reservoir compartment ( a liquid drug formulation
inside a collapsible, impermeable container).
• Contained inside a rigid, shape- retaining housing.
• A laminate of an absorbent layer and a swellable, hydrophilic
polymer layer is sandwiched between the drug reservoir
compartment and the housing.
• In the GIT, the laminate will imbibe the gastrointestinal fluid-
-through the annular openings at the lower end of the
housing and become swollen.
• Generates a hydrodynamic pressure in the system.
Contdd……
13

14. • Forces the drug reservoir compartment to reduce in volume.
• Causes the liquid drug formulation to release through the
delivery orifice.
View of a hydrodymanic pressure activated system
In this type the hydrodynamic pressure is used as a source of
energy to activate the drug release.
14

15. • The rate of drug release is defined by following equn:-
• Where, Pw, Am, & hm are the fluid permeability, the effective
surface area and the thickness of the wall with annular opening
respectively.
• The (Өs-Өe) is the difference in hydrodynamic pressure
between the drug delivery system and the environment.
• Controlled release rate is determined by:-
1) Fluid permeability.
2) Effective surface area.
3) Hydrodynamic pressure gradient.
)( es
hm
PwAm
t
Q
 
15

16. Vapor Pressure-activated DDS:
• The drug reservoir (a solution formulation contained inside the
infusion compartment).
• Physically separated from the pumping compartment by a
freely movable partition.
• The pumping compartment contains:-
A vaporizable fluid, such as fluorocarbon
Drug
Implantation
site
Due to body
temperature
Vaporization of
fluorocarbon
fluid
Vapor pressure
created
Partition
moves upwards
Forces drug
solution to be
delivered
16

17. • The delivery of drug
- Activated by vapor pressure
- Controlled at a rate determined by:
- The differential vapor pressure
- The formulation viscosity
- The size of delivery cannula
Example:
• Implantable infusion pump (infusaid) for the constant infusion
of:-
- Heparin in anticoagulant treatment
- Insulin in anti-diabetic treatment
- Morphine for the intense pain of terminal cancer.
17

18. Mechanically Activated DDS:
• The drug reservoir (solution formulation retained in a
container equipped mechanically activated pumping system).
• A measured dose of drug formulation:
- Delivered to body cavity such as nose, through the spray head
- Upon manual activation of pumping system.
• The volume of solution delivered is small (10-100µl).
• Independent of the force and duration of activation.
Example: ( MDI)
For the intranasal administration of a precision dose of :
-Buserelin
- Insulin
18

19. Magnetically Activated DDS:
• The drug reservoir is dispersion of peptides or protein powder in a
polymer matrix from which drug can be delivered relatively at
slow rate.
• Can be improved by electromagnetism-triggering vibration
mechanism & with a hemisphere- shaped design, a zero order
drug release is achieved.
• Hemisphere devices can release macromolecular drug
-At low rate, by diffusion process.
- At high rate, when magnet is activated, to vibrate by external
electromagnetic field.
19

20. • Factors affecting:-
- Strength of magnetic field
- Mechanical properties of the polymer matrix
Example:
Used to deliver protein drugs such as BOVINE SERUM
ALBUMIN.
20

21. Sonophoresis Activated DDS:
• This type of activation controlled drug delivery system utilizes
ultrasonic energy to activate (or trigger) the delivery of drug
from polymeric drug delivery devices.
Ultrasonic Waves
Stimulate micro-
vibration
Within skin
epidermis
Increase kinetic
energy of
molecule
When sound is
emitted at
particular
frequency
Disrupts the lipid
bilayer
Penetrates the
drug
21

22. • This system can be fabricated from either a non-biodegradable
polymer such as ethylene- vinyl acetate co polymer or a bio-
erodible polymer.
• Example: It has been explored to promote ocular drug
delivery
Application of ultrasound to activate the delivery of drug
22

23. Iontophoresis activated DDS:
• Primarily used in transdermal delivery.
• In this, delivery system uses electrical current to activate & to
modulate the diffusion of the charged drug molecules across
the skin.
• The iontophoresis facilitated skin permeation rate of a charged
molecules.
Basic Mechanism:-
“Like charges repel and opposite charges attract.”Positively
charged drugs are paced at positive pole, while negatively
charged peptides are placed at negative pole.
Electrorepulsion of like charges and attraction of opposite
charges push the drug across the membrane.
23

24. cntd…
• Example: Iontophoresis DDS to facilitate the percutaneous
penetration of Dexamethasone sodium phosphate (anti-
inflammatory).
Representation of iontophoresis activated system
24

25. Hydration Activated DDS:
• In this the drug reservoir is
homogenously dispersed in a
swellable polymer matrix
fabricated from hydrophilic
polymer (ethylene
glycomethacrylate).
• The release of drug is controlled
by the rate of swelling of the
polymer matrix.
• Example:- Norgestomet
releasing HYDRON implant
- The VALRELEASE tab
Hydration-induced formation of
colloidal gel barrier
25

26. Chemical Means:-
26

27. pH Activated DDS:
• This system permits targeting the delivery of a drug only in the
region with a selected pH range.
• Fabricated by coating the drug core with a pH sensitive
polymer
• Example:- Gastric fluid labile
drug
Coated with
Ethylcellulose +
HMCP( Enteric
coated)
Resist the degradation
in acidic pH (pH<3)
Protected from acidic
degradationGastric emptying
Comes in small
intestine
Intestinal fluid
dissolve the coated
membrane due to high
pH (pH >7.5)
Leaves a microporous
membrane
constructed from
ethylcellulose
This membrane
control the release of
drug from the core
tablet
27

28. ctnd…
pH – dependent formation of micro-porous membrane
• Note: By adjusting the ratio of intestinal fluid soluble polymer
to the intestinal fluid insoluble polymer, the membrane
permeability is modified.
.
28

29. Ion-Activated DDS:
Delivery system are
prepared by complexing
an ionic drug with an
ion-exchange resin
containing a suitable
counter ion
Cationic drug + SO3
‾
group
Anionic drug+
[N{CH3}3]+ group
Granules of drug resin
complex treated with
impregnating agent
Then coated with a
water-insoluble but
water- permeable
membrane
This membrane serve as
a rate controlling barrier
When the delivery
system is present in
electrolyte medium like
gastric fluid
Ion diffuse into the
system, react with the
drug resin complex
Trigger the release of
ionic drug.
29

30. cntd….
• H+ + Resin- SO3
‾ * Drug+ Resin-SO3
‾ *H+ + Drug‾
• Cl‾ + Resin-[N{CH3}3]+* Drug‾ [N{CH3}3]+ *Cl‾ + Drug+
Diagram of Ion-activated drug release
30

31. 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
homogenously dispersed in microspheres .
• Can also be fabricated as an implantable device.
• Systems prepared from biodegradable polymers.
• It is activated by hydrolysis-induced degradation of polymer
chain & is controlled by rate of polymer degradation.
• Example: Releasing biodegradable subdermal implants,
designed to deliver goserline for once a month treatment of
prostate carcinoma.
31

32. Biochemical Means:-
32

33. Enzyme-Activated DDS:
• This type of biochemical system depends on the enzymatic
process to activate the release of drug.
• Drug reservoir-
- physically entrapped in microsphere or,
- chemically bound to polymer chains from
biopolymers(albumins or polypeptides)
• The release of drug is activated by enzymatic hydrolysis of
biopolymers by specific enzyme in target tissue.
Example: Albumin microspheres release 5- fluorouracil in a
controlled manner by protease- activated biodegradation.
33

34. REFERENCES:
Y.W.Chien; Novel Drug Delivery System, 2nd ed, pg no.
24-40
R. Tiwari; Controlled release drug formulation in
pharmaceuticals: A study on their application and
properties. World Journal of Pharmaceutical Research,
5(2), 1704-1720
S.P.Vyas, K.Khar; Controlled Drug Delivery Concepts
and Advances, 1st edition, pg no.1-41
www.google.com
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