rate controlled drug delivery system

1. Rate controlled drug delivery
system
Presented By : Facilitated To:
Nagond Mukund m Dr. Anita Desai
M.Pharm 1st year HOD and Professor
Dept. of Pharmaceutics Dept. of Pharmaceutics
HSKCOP, BAGALKOT. HSKCOP, BAGALKOT

2. Contents
• Definition
• Types of RCDDS
• Classification

3. WHAT IS CONTROLLED RELEASE?
The term "Controlled release" has become associated
with those systems from which therapeutic agents may be
automatically delivered at predefined rates over a long period
of time.
WHAT IS CONTROLLED RELEASE FORMULATIONS?
These are the formulations which delivers the drug at
a predetermined rate, for locally or systematically , for a
specified period of time.
Example : GITS - Prazosin (mini press)
Morphine sulphate ( Roxonal SR)

4. • Types of RCDD
Further Classified into:
a)Dissolution controlled DDS
b)Diffusion controlled DDs
c)Erosion controlled DDS
d)Combination of dissolution, diffusion, and erosion controlled DDS
a)Dissolution controlled DDS:
• These systems are those where the limiting phenomenon responsible
for imparting the controlled release characteristics to the DDS is
either
A)Slow dissolution rate of the drug:
The drug present in this system may be
• Drug with inherently slow dissolution rate:
Example: Griseofulvin, digoxin and nifedipine.
• Drug that transforms into a slow dissolving form on contact with GI
fluids
Example: Ferrous sulphate

6. B)Slow dissolution rate of the reservoir membrane or matrix:
The drug present in such a system may be the one having high aqueous
solubility & dissolution rate. Example: pentoxifylline and metformin.
The challenge in designing such systems lies in controlling the drug
dissolution rate by employing either or combination by following
techniques:
• Embedment in slowly dissolving , degrading or erodible matrix. The
matrix in addition may have low porosity or poor wettability.
• Encapsulation or coating with slow dissolving, degrading or erodible
substances. In this approach, the rate of dissolution fluid penetration
or wettability of the reservoir system are controlled.

7. b)Diffusion controlled DDS:
• The system where the rate controlling step is not the dissolution rate
of drug or release controlling element, but diffusion of dissolved drug
molecule through the rate controlling element. The rate controlling
element in such system is thus insoluble, non-erodible & non
degradable.
Porous matrix controlled systems:

8. Porous membrane controlled systems:
c)Erosion controlled DDs:
• It is defined as physical degradation of a polymer/wax matrix or
coating as a result of degradation and characterized by material loss
from the polymer generally in the physical state. The pH change due
to osmotic pressure(exerted by dissolved drug/excipients) or by
hydrodynamic pressure(exerted by excipients that imbibe water &
swell) that causes fragmentation.

9. • 1.Surface erosion: also called heterogeneous erosion
• 2.Bulk erosion: also known as homogeneous erosion

10. d)Dissolution, Diffusion or erosion controlled DDS:
• The rate of drug is controlled by drug or polymer dissolution,
drug diffusion or polymer erosion i.e, this system is a
combination of two or more systems.

11. CLASSIFICATION:
Depending upon the sophistication of the technology in
use controlled release delivery system can be classified into
these fallowing three types
1)Rate preprogrammed drug delivery system
2)Activation-modulated drug delivery system
3)Feedback-regulated drug delivery system
All these three types of controlled release drug delivery
system consist of the following structural features
1) Drug reservoir compartment
2) Rate controlling element
3) Energy source

13. Controlled release
system
Dissolution
controlled
Diffusion and Dissolution
controlled
Diffusion controlled
Water penetration
controlled
Chemically
controlledHydrogels
Ion exchange resin
Encapsulation
Matrix
Matrix
Reservoir
Reservoir and
Monolithic
Osmotically
controlled
Swelling
controlled
Erodible
systems
Drug covalently
linked with polymer
Chemically
controlled
Swelling
controlled
Diffusion
controlled
Cation
exchange
Anion
exchange
Shematic structure of various
classes of Controlled Release
System

14. 1)Rate preprogrammed drug delivery system
These type of controlled release drug delivery systems the
release of drug molecules from the delivery systems has been
preprogrammed at specific rate profiles. This was done by system
design, which controls the molecular diffusion of drug molecule
in/or across the barrier medium within or surrounding the delivery
system
These systems can be further divided as fallows:
• Polymer Membrane Permeation-Controlled DDS
• Polymer Matrix Diffusion-Controlled DDS
• Microreservoir Partition-Controlled DDS

15. A. Polymer Membrane Permeation-Controlled DDS
The drug reservoir is totally encapsulated in a shallow-compartment
molded from a drug impermeable metallic plastic laminate and a rate
controlling polymeric membrane which may be micro-porous and non-
porous.
The rate of drug release from this type of TDDS,can be tailored by
varying the composition of polymer permeability coefficient ,thickness
of the rate limiting membrane ,and adhesive .
 e.g.: nitroglycerine releasing transdermal systems for once a day
medication in angina pectoris

16. 1.TDDS
2.IUD

17. 3.Norplant subdermal implant
4.Ocusert system

18. B. Polymer Matrix Diffusion-Controlled DDS
Prepared by homogenously dispersing the drug particles with a liquid
polymer or a highly viscous base polymer followed by cross linking of
the polymer chains or homogenously blending the drug solids with a
rubbery polymer at an elevated temperature.
It can be prepared by dissolving the drug and the polymer in a
common solvent followed by solvent evaporation in a mould at an
elevated temperature or in a vacuum.
It is then pasted on to an occlusive base plate in a compartment
fabricated from a drug impermeable plastic backing, the adhesive
polymer is then spread along the circumference to form a strip of
adhesive rim around the medicated disc.
E.g.: nitroglycerine releasing transdermal system(Nitro- Dur II) for
therapy of angina pectoris.

20. C. Microreservoir Partition-Controlled DDS
Drug reservoir is formed by first suspending the drug solids in an
aqueous solution of a water soluble liquid polymer and then dispersing
the drug suspension homogenously in a lipophilic polymer such as
silicone elastomers by high dispersion technique.
E.g.: nitroglycerine releasing transdermal system (Nitro disc) for once a
day therapy for angina pectoris.

21. 2)Activation-modulated drug delivery system
In this group of controlled-release drug delivery systems the
release of drug molecules from the delivery systems is activated by
some physical, chemical or biochemical processes and/or facilitated
by the energy supplied externally.

22. Activation modulated drug delivery systems(DDS) can be classified into
the following categories:
1. Physical means
a. osmotic pressure activated DDS
b. hydrodynamic pressure activated DDS
c .vapor activated DDS
d. mechanically activated DDS
e. magnetically activated DDS
f. sonophoresis activated DDS
g. iontophoresis activated DDS
h. hydration-activated DDS
2. Chemical means
a. pH-activated DDS
b. ion-activated DDS
c. hydrolysis-activated DDS
3. Biochemical means
a enzyme activated DDS
b. biochemical-activated DDS

23. Hydrodynamic pressure activated DDS
• These are identical to osmotic systems which releases drug at zero
order rate. It differs from osmotic system in that a hydrodynamic
pressure generating agent, which is typically a water swellable
hydrocolloid such as HPMC, which is contained in one compartment
& drug solution is present in another collapsible reservoir. The
hydrocolloid imbibes water & swells to generate hydrodynamic
pressure that pushes the drug reservoir compartment & thus it forces
the drug through an orifice at slow and uniform rate.

25. Mechanically activated drug delivery systems
• In this type of activation-controlled drug delivery system the drug
reservoir is a solution formulation retained in a container equipped
with mechanically activated pumping system.
• The volume of solution delivered is controllable as small as 10-100μl.
• The volume of solution delivered is independent of the force and
duration of activation applied as well as the solution volume in the
container.
• Example is the development of the metered-dose nebulizer
• for the intranasal administration of a precision dose of buserelin,
which is a synthetic analog of luteinizing hormone releasing hormone
(LHRH) and insulin.

27. Magnetically activated DDS
• In this system a tiny doughnut shaped magnet is positioned in the
centre of a hemispherical shaped biocompatible polymer matrix
containing dispersed drug and then coating the external surface of
the medicated polymer matrix. When the magnet is activated to
vibrate by an external electromagnetic field, it releases the drug at a
zero order rate by diffusion process.

28. Vapor activated DDS
• pumping compartment & the drug solution compartment are
separated by a freely movable partition. The pumping compartment
contains a liquefied compressed gas that vaporizes at body
temperature and creates vapour pressure.
Example: the development of infusion pumps of heparin in
anticoagulant therapy, of insulin in the control of diabetes and of
morphine for patients suffering from the intensive pain of a terminal
cancer.

29. Ph-Activated drug delivery systems
• This type of DDS permits targeting the delivery of a drug only in the
region with a selected pH range.
• Intestinal pH activated DDS
• It is fabricated by coating the drug containing core with a pH sensitive
polymer combination.
• A gastric fluid labile drug is protected by encapsulating it inside a
polymer membrane that resist the degradative action of gastric ph.
such as the combination of ethyl cellulose and HMC phthalate.
• The drug is release by drug dissolution and pore channel diffusion
mechanism.

31. • In the stomach the coating membrane resists the action of gastric
fluid (ph < 3) and the drug ,molecules are thus protected from acid
degradation.
• After gastric emptying the drug delivery system travels to the small
intestine and the intestinal fluid activates the erosion of the intestinal
fluid-soluble HMC phthalate component from the coating membrane.
• By adjusting the ratio of the intestinal fluid soluble polymer to the
intestinal fluid insoluble polymer, the membrane permeability of a
drug can be regulated as desired.

32. Sonophoresis activated DDS
• This type of activation-controlled drug delivery systems utilizes
ultrasonic energy to activate (or trigger) the delivery of drugs from a
polymeric drug delivery device.
• The system can be fabricated from either a nondegradable polymer,
or a bioerodible polymer.

33. Iontophoresis activated DDS
• This type of activation-controlled drug delivery systems uses
electrical current.
• For activate and to modulate the diffusion of a charged drug
molecule across a biological membrane, like the skin.
• The iontophoresis-facilitated skin permeation rate of a charged
molecule.

34. Osmotic activated drug delivery system
• Osmosis can be defined as the net movement of water across a
selectively permeable membrane driven by a difference in osmotic
pressure across the membrane.
• It is driven by a difference in solute concentrations across the
membrane that allows passage of water, but rejects most solute
molecules or ions.
• Osmotic pressure created by osmogen is used as driving force for
these systems to release the drug in controlled manner.
• Osmotic pump offers many advantages over other controlled drug
delivery systems, that is,
 they are easy to formulate.
 simple in operation.
 improved patient compliance with reduced dosing frequency and
more consistence.

35.  prolonged therapeutic effect with uniform blood concentration.
 inexpensive and their production scale up is easy.
• Osmotic drug-delivery systems suitable for oral administration
typically consist of a compressed tablet core that is coated with a
semipermeable membrane coating.
• This coating has one or more delivery ports through which a solution
or suspension of the drug is released over time.
• The core consists of a drug formulation that contains an osmotic
agent and a water swellable polymer.
• The rate at which the core absorbs water depends on the osmotic
pressure generated by the core components and the permeability of
the membrane coating.
• As the core absorbs water, it expands in volume, which pushes the
drug solution or suspension out of the tablet through one or more
delivery ports.

36. • Materials used in formulation of osmotic system:
1. semipermeable membrane
2. hydrophilic and hydrophobic polymers
3.wicking agents
4. solubilizing agents
5.osmogens
6.surfactants
7.coating solvents
8. plasticizers
9. pore forming agents

37. 1. Semipermeable membrane:
• Cellulose acetate is a commonly employed semipermeable polymer
for the preparation of osmotic pumps.
• It is available in different acetyl content grades. Particularly, acetyl
content of 32% and 38% is widely used.
• Some of the polymers that can be used for above purpose include
cellulose esters such as cellulose acetate, cellulose diacetate,
cellulose triacetate, cellulose propionate, cellulose acetate butyrate,
and cellulose ethers like ethyl cellulose.
• Apart from cellulose derivatives, some other polymers such as agar
acetate, amylose triacetate, betaglucan acetate, poly(vinyl methyl)
ether copolymers, poly(orthoesters), poly acetals and selectively
permeable poly(glycolic acid), poly(lactic acid) derivatives, and
Eudragits can be used as semipermeable film-forming materials

38. 2. hydrophilic and hydrophobic polymers
• These polymers are used in the formulation development of osmotic
systems for making drug containing matrix core.
• The highly water soluble compounds can be coentrapped in
hydrophobic matrices and moderately water soluble compounds can
be coentrapped in hydrophilic matrices to obtain more controlled
release.
• The polymers are of either swellable or nonswellable nature. Mostly,
swellable polymers are used for the pumps containing moderately
water-soluble drugs.
• Ionic hydrogels such as sodium carboxymethyl cellulose are
preferably used because of their osmogenic nature.
• Hydrophilic polymers such as hydroxy ethyl cellulose, carboxy
methylcellulose, hydroxy propyl methylcellulose, highmolecular-
weight poly(vinyl pyrrolidone), and
• hydrophobic polymers such as ethyl cellulose and wax materials can
be used for this purpose.

39. 3.wicking agents
• A wicking agent is defined as a material with the ability to draw water into
the porous network of a delivery device.
• The wicking agents are those agents which help to increase the contact
surface area of the drug with the incoming aqueous fluid.
• The use of the wicking agent helps to enhance the rate of drug released
from the orifice of the drug.
• A wicking agent is of either swellable or nonswellable nature .
• They are characterized by having the ability to undergo physisorption with
water.
• Physisorption is a form of absorption in which the solvent molecules can
loosely adhere to surfaces of the wicking agent via Vander Waals
interactions between the surface of the wicking agent and the adsorbed
molecule.
• The function of the wicking agent is to carry water to surfaces inside the
core of the tablet, thereby creating channels or a network of increased
surface area .
• The examples are colloidal silicon dioxide, PVP and Sodium lauryl sulfate.

40. 4. Solubilizing agents
• For osmotic drug delivery system, highly water-soluble drugs would
demonstrate a high release rate that would be of zero order.
• Thus, many drugs with low intrinsic water solubility are poor
candidates for osmotic delivery. However, it is possible to modulate
the solubility of drugs within the core.
• Addition of solubilizing agents into the core tablet dramatically
increases the drug solubility.

41. 5.Osmogens
• Upon penetration of biological fluid into the osmotic pump through
semipermeable membrane, osmogens are dissolved in the biological
fluid, which creates osmotic pressure buildup inside the pump and
pushes medicament outside the pump through delivery orifice.
• They include inorganic salts and carbohydrates.
• Mostly, potassium chloride, sodium chloride, and mannitol used as
osmogens.
• Generally combinations of osmogens are used to achieve optimum
osmotic pressure inside the system

42. 6.Surfactants
• Surfactants are particularly useful when added to wall-forming
material.
• The surfactants act by regulating the surface energy of materials to
improve their blending into the composite and maintain their
integrity in the environment of use during the drug release period.
• Typical surfactants such as poly oxyethylenated glyceryl recinoleate,
polyoxyethylenated castor oil having ethylene oxide, glyceryl laurates,
and glycerol (sorbiton oleate, stearate, or laurate) are incorporated
into the formulation.

43. 7.Coating solvents
• Solvents suitable for making polymeric solution that is used for
manufacturing the wall of the osmotic device include inert
inorganic and organic solvents that do not adversely harm the
core and other materials.
• The typical solvents include methylene chloride, acetone,
methanol, ethanol, isopropyl alcohol, butyl alcohol, ethyl acetate,
cyclohexane, carbon tetrachloride, and water.

44. 8. Plasticizers
• Plasticizers, or low molecular weight diluents are added to modify the
physical properties and improve film-forming characteristics of
polymers.
• Plasticizers can change visco elastic behavior of polymers significantly
.
• Plasticizers can turn a hard and brittle polymer into a softer, more
pliable material, and possibly make it more resistant to mechanical
stress .
• PEG-600, PEG-200, triacetin (TA), dibutyl sebacate, ethylene glycol
monoacetate, ethylene glycol diacetate, triethyl phosphate, and
diethyl tartrate used as plasticizer in formulation of semipermeable
membrane .

45. 9. Pore forming agents
• These agents are particularly used in the pumps developed for poorly
water-soluble drugs and in the development of controlled porosity or
multiparticulate osmotic pumps .
• These pore-forming agents cause the formation of microporous
membrane.
• The pore-formers can be inorganic or organic and solid or liquid in
nature.
 For example,
 alkaline metal salts such as sodium chloride, sodium bromide,
potassium chloride, potassium sulphate, potassium phosphate, and
so forth,
 alkaline earth metals such as calcium chloride and calcium nitrate,
carbohydrates such as sucrose, glucose, fructose, mannose, lactose,
sorbitol, and mannitol, and
 diols and polyols such as poly hydric alcohols, polyethylene glycols,
and polyvinyl pyrrolidone can be used as pore-forming agents .

46. Creation of Delivery Orifice
• Osmotic delivery systems contain at least one delivery orifice in the
membrane for drug release.
• On the other hand, size of delivery orifice should not also be too
large, otherwise, solute diffusion from the orifice may take place.
• Optimum orifice diameter is in the range of 0.075–0.274 mm. At
orifice size of 0.368 mm and above, control over the delivery rate is
lost .
• If the size of delivery orifice is too small, zero-order delivery will be
affected because of development of hydrostatic pressure within the
core.
• Delivery orifices in the osmotic systems can be created with the help
of a mechanical drill .
• Laser drilling is one of the most commonly used techniques to create
delivery orifice in the osmotic tablet.

47. • Types of Osmotic Pumps
1) Rose-Nelson Pump
2) Higuchi-Leeper Osmotic Pump
3) Higuchi-Theeuwes Osmotic Pump
4) Elementary Osmotic Pump (EOP)
5) Push-Pull Osmotic Pump (PPOP)
6) Controlled Porosity Osmotic Pump (CPOP)
7) Liquid-Oral Osmotic (L-OROS) System
8) Sandwiched Osmotic Tablet (SOT)

48. 1.Rose-Nelson Pump
• Rose and Nelson, the Australian scientists, were initiators of osmotic
drug delivery. In 1955, they developed an implantable pump for the
delivery of drugs to the sheep and cattle gut.
• The Rose-Nelson implantable pump is composed of three chambers:
a drug chamber, a salt chamber holding solid salt, and a water
chamber.
• A semipermeable membrane separates the salt from water chamber
• The movement of water from the water chamber towards salt
chamber is influenced by difference in osmotic pressure across the
membrane.
• Conceivably, volume of salt chamber increases due to water flow,
which distends the latex diaphragm dividing the salt and drug
chambers: eventually, the drug is pumped out of the device.

49. • The major problem associated with
• Rose-Nelson pumps was that the osmotic action began whenever
water came in contact with the semipermeable membrane. This
needed pumps to be stored empty and water to be loaded prior to
use.

50. 2.Higuchi-Leeper Osmotic Pump
• The Higuchi-Leeper pump has no water chamber, and the activation
of the device occurs after imbibition of the water from the
surrounding environment.
• Higuchi-Leeper pumps contain a rigid housing and a semi permeable
membrane supported on a perforated frame; a salt chamber
containing a fluid solution with an excess of solid salt.
• Upon administration/implantation, surrounding biological fluid
penetrates into the device through porous and semipermeable
membrane and dissolves the MgSO4, creating osmotic pressure
inside the device that pushes movable separator toward the drug
chamber to remove drug outside the device.
• It is widely employed for veterinary use.

51. 3. Higuchi-Theeuwes Osmotic Pump
• In this device, the rigid housing consisted of a semipermeable
membrane.
• This membrane is strong enough to withstand the pumping pressure
developed inside the device due to imbibition of water.
• The drug is loaded in the device only prior to its application, which
extends advantage for storage of the device for longer duration.
• They are used frequently as implantable controlled release delivery
systems in experimental studies requiring continuous administration
of drugs.

52. 4. Elementary Osmotic Pump (EOP)
• Elementary osmotic pump was invented by Theeuwes in 1974 .
• It essentially contains an active agent having a suitable osmotic
pressure; it is fabricated as a tablet coated with semi permeable
membrane, usually cellulose acetate .
• A small orifice is drilled through the membrane coating.
• When this coated tablet is exposed to an aqueous environment, the
osmotic pressure of the soluble drug inside the tablet draws water
through the semi permeable coating and a saturated aqueous
solution of drug is formed inside the device.
• The membrane is nonextensible and the increase in volume due to
imbibition of water raises the hydrostatic pressure inside the tablet,
eventually leading to flow of saturated solution of active agent out of
the device through a small orifice.

53. 5.Push-Pull Osmotic Pump (PPOP)
• Push-pull osmotic pump is delivered both poorly water soluble and
highly water soluble drugs at a constant rate.
• This system resembles a standard bilayer coated tablet. One layer
(the upper layer) contains drug in a formulation of polymeric osmotic
agent, and other tablet excipients.
• When the system is placed in aqueous environment, water is
attracted into the tablet by an osmotic agent in both the layers.
• The osmotic attraction in the drug layer pulls water into the
compartment to form in situ a suspension of drug.
• The osmotic agent in the nondrug layer simultaneously attracts water
into that compartment, causing it to expand volumetrically, and the
expansion of nondrug layer pushes the drug suspension out of the
delivery orifice .

54. 6.Controlled Porosity Osmotic Pump (CPOP)
• Controlled porosity osmotic pump (CPOP) are reliable drug delivery
system and could be employed as oral drug delivery system.
• CPOP consists of drug and osmogen in the core and tablet is
surrounded by a semipermeable membrane containing leachable
pore forming agents which in contact with aqueous environment
dissolves and result in formation of micro porous membrane.
• Drug release rate from CPOP depends on various factors like
• Coating thickness,
• Solubility of drug in tablet core,
• Level of leachable pore-forming agent(s) and
• The osmotic pressure difference
across the membrane.

55. 7.Liquid-Oral Osmotic (L-OROS) System
• Each of these systems includes a liquid drug layer, an osmotic engine
or push layer, and a semipermeable membrane coating.
• When the system is in contact with the aqueous environment, water
permeates across the rate-controlling membrane and activates the
osmotic layer.

56. 8.Sandwiched Osmotic Tablet (SOT)
• Sandwiched osmotic tablet is composed of polymeric push layer
sandwiched between two drug layers with two delivery orifices.
• When placed in the aqueous environment, the middle push layer
containing the swelling agents' swells and the drug is released from
the two orifices situated on opposite sides of the tablet; thus
sandwiched osmotic tablets (SOTS) can be suitable for drugs prone to
cause local irritation of the gastric mucosa.

57. Enzyme activated drug delivery systems
• This type of activation modulated DDS depends on the enzymatic
process to activate the release of the drug.
• In this system the drug reservoir is either physically entrapped in
microspheres or chemically bound to the polymer chains from
biopolymers, such as albumins or polypeptides.
• The release of drug is activated by the enzymatic hydrolysis of
biopolymers by a specific enzyme in the target tissue.
• Typical example of this enzyme activated DDS is the development of
albumin microspheres that release 5fluorouracil in a controlled
manner by protease activated biodegradation.

58. Feedback regulated drug delivery system
• In this group of controlled-release DDS the release of drug molecules
from the delivery systems is activated by triggering agent, such as a
biochemical substance, in the body.
• The rate of drug release is then controlled by the concentration of
triggering agent detected by a sensor in the feedback-regulated
mechanisms.
• It is classified in to the following:
1) Bioerosion-regulated drug delivery systems
2) Bioresponsive drug delivery systems
3) Self regulating drug delivery systems

59. Bioerosion-regulated drug delivery systems
• The feedback-regulated DDS was applied to the development of a
bioerosion-regulated DDS by heller and trescony.
• The system consisted of drug dispersed bioerodible matrix fabricated
from poly(vinyl methyl ether) half-ester , which was coated with a
half layer of immobilized urease.
• In a solution of neutral pH, the polymer only erodes slowly.
• In the presence of urea, urease at the surface of DDS metabolizes
urea to form ammonia.
• This causes the pH to increase and a rapid degradation of polymer
matrix as well as the release of drug molecules.

60. Fig:-Cross-sectional view of a bioerosion-regulated hydrocortisone delivery system,
showing the drug-dispersed monolithic bioerodible polymer matrix with surface-
immobilized ureases.

61. Bioresponsive drug delivery systems
• Bioresponsive DDS was developed by Horbett et al.
• Drug reservoir is contained in a device enclosed by a bioresponsve
polymeric membrane whose drug permeability is controlled by the
concentration of a biochemical agent in the tissue where the system
is located.
• Typical example of this bioresponsive DDS is the development of a
glucose-triggered insulin delivery system in which the insulin
reservoir is encapsulated within a hydrogel membrane having
pendent NR2 groups.
• In alkaline solution the – NR2 groups are neutral and the membrane
is unswollen and impermeable to insulin.
• Glucose is a triggering agent, penetrates in to the membrane , it is
oxidized enzymatically by the glucose oxidase entrapped in the
membrane to form gluconic acid.
• The –NR2 groups are protonated to form –NR2H and the hydrogel
membrane then becomes swollen and permeable to insulin
molecules.

62. Fig:-Cross-sectional view of a bioresponsive insulin delivery system, showing the glucose
oxidase-entrapped hydrogel membrane constructed from amine-containing hydrophilic
polymer. The mechanism of insulin release in response to the influx of glucose is also
illustrated.

63. Self regulating drug delivery systems
• This type of feedback-regulated drug delivery system depends on a
reversible and competitive binding mechanism to activate and
regulate the release of the drug.
• In this system the drug reservoir is drug complex encapsulated
within a semipermeable membrane polymeric membrane.
• The release of drug is activated by the polymeric membrane of a
biochemical agent from the tissue in which the system is located.
• It first involves the reparation of biologically active insulin derivatives
in which insulin is coupled with a sugar (maltose) and this into an
insulin-sugar-lectin complex.
• Complex is then encapsulated within a semipermeable membrane.
• As blood glucose diffuses into the device and competitively binds at
the sugar binding sites in lectin molecules.
• This activates the release of bound insulin-sugar derivatives.

64. • Complex of glycosylated insulin-concanavalin A, which is
encapsulated inside a polymer membrane.
• As glucose, the triggering agent, penetrates the system, it activates
the release of glycosylated insulin from the complex for controlled
delivery out of the system.

65. • References:
1. Novel drug delivery systems by Yie W. Chein. Pg no 1 – 37
2. Osmotic drug delivery systems
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407637/
3. Images from Google

66. Thank you