As per the syllabus of M.Pharma (1st sem.) I have presented the topic pH-activated and Enzyme-activated. This comes under rate-controlled drug delivery system under the subject Drug delivery system. Best wishes from Sakshi Sharma

1. Presented By:
SAKSHI SHARMA
M.PHARM (PHARMACEUTICS), 1st sem.
Pranveer Singh Institute of Technology, Kanpur

2. 1.Introduction
2. Rationale
3. pH-activated drug delivery system
a) Examples of pH-sensitive polymers
b) pH sensitive polymers
c) Intestinal pH-activated drug delivery system
4. Enzyme-activated drug delivery system
a) Examples of enzyme-sensitive polymers
b) Typical enzymes for CDDS

3.  The drug delivery system which delivers the drug
at a predetermined rate, for locally or
systemically, for a specified period of time is
called Rate-controlled Drug delivery system.
 These systems are capable of controlling the rate
of drug delivery by sustaining the duration of
therapeutic efficacy or targeting the drug
delivery.
 These are able to specify the release rate and
duration in-vivo precisely, on the basis of simple
in-vitro tests.
 Controlled release is a kind of zero order release
i.e. the drug release over time irrespective of
concentration.

4. To optimize the biopharmaceutics,
pharmacokinetics, and pharmacodynamics
properties of a drug in such a way that:
Its utility is maximized through reduction in side
effects
Cure or control of disease condition in the
shortest
possible time by using smallest quantity of drug
Administered by most suitable route.
An ideal drug delivery system should deliver the
drug at a rate dictated by the need of body over a
specified period of treatment.

5. This is by chemical means.
This type of chemically-activated system permits
targeting of drug delivery only in the region with
selected or specific pH range.
It is fabricated by coating the drug-containing
core with a pH-sensitive polymers combination.

6. Example of pH-sensitive Polymers:-
Polymer Groups attached Swells in pH
Chitosan -NH2 , -OH Acidic
Guar gum (semi-
natural)
-COOH Basic
Gelatin A & B -NH2, -OH Acidic
Hyaluronic acid -COOH, -OH Basic

7. pH- sensitive polymers:-
oResponds to changes in pH of surrounding medium.
oExpands or collapse depending on pH of environment
of body.
oDue to presence of certain functional groups in the
polymer chain i.e.
1. Acidic group (-COOH, -SO3H)
2. Basic group (-NH2)
oAfter ionization of these groups:- hydrodynamic volume
increases due to electrostatic repulsion.

8. Intestinal pH-activated drug delivery system
Drug is released by drug dissolution and pore channel diffusion mechanism.
In stomach coating membrane resists the action of gastric fluid(pH<3) and the
drug molecule thus protected from acidic degradation.
After gastric emptying, the DDS travels to small intestine where pH>7.5. It
activates the erosion of the intestinal fluid soluble polymer from the drug.
This leaves a microporous membrane constructed from the intestinal fluid
insoluble polymer which controls the release of drug from the core tablet.
The drug solute is thus, delivered at a controlled manner in the intestine by a
combination of drug dissolution and pore channel diffusion.

9. Enzyme-activated drug delivery
system:
oThis is by Biochemical means.
oIt is also a kind of activation modulated DDS.
oThis type of system depends upon enzymatic processes to
activate the drug release i.e. it requires an external stimuli to
activate the release of drug.
oThen it may follow any of these two types of mechanism i.e.
either drug reservoir is either physically entrapped in microsphere
or chemically bound to polymer chains from biopolymers.
oThe release of drug is activated by enzymatic hydrolysis of
biopolymer by specific in target tissue.
oEnzyme sensitive layer is unable to bear the enzyme reaction and
thus it breaks.

11. Example of Enzyme sensitive polymers:-
Enzyme-sensitive
polymers
Enzymes Enzyme-sensitive
functionality
PEG Trypsin D-AFK
PEG Papain GGG
Gelatin Alpha-chymotrypsin Gelatin
Dextran cross-linked
with diisocyanate
Dextranase Dextran

12. Typical enzymes for CDDS:-
Matrix Metalloproteases (MMP) = involved in many physiological
processes such as tissue remodeling, wound healing and tumour
invasion.
MMP subtypes are divided into 2 classes:-
1. Transmembrane enzymes – have 6 subtypes
2. Extra-cellular enzymes – have 18 subtypes
MMP plays vital role in invasion, angiogenesis and metastasis to
cancer. They are proteolytic enzymes causing degradation of
protiens which regulates various cell behavior for cancer biology.

13. Mostly enzymes degradable polymers are formulated with Type A Gelatin
cross-linked with glutaraldehyde in which PEG-stabilized quantum dots are
distributed.
Polymers moves out of blood vessels by enhanced permeation and Retention
effect (EPR).
Polymers are exposed to upregulated matrix metalloproteinases (MMP-2)
Polymers are degraded by MMP
10nm quantum dots release
Enhancement of diffusion transport and deep penetration in tumour tissues.