The document discusses various types of drug delivery systems, focusing on rate-controlled drug delivery mechanisms. It contrasts sustained release and controlled release systems, outlines their advantages and disadvantages, and details classifications such as rate-preprogrammed, activation-modulated, feedback-regulated, and site-specific systems. The seminar highlights advancements in drug delivery technology, emphasizing controlled drug release rates and targeting specific tissues for therapeutic benefits.

1. DRUG DELIVERY SYSTEM
SEMINAR: RATE CONTROLLED DRUG DELIVERY SYSTEM
SUBMIITTED TO:
Dr. Gurpreet Kaur
SUBMIITTED BY:
Ankush Kumar
DEPARTMENT OF PHARMACEUTICAL SCIENCES AND DRUG RESEARCH,
PUNJABI UNIVERSITY, PATIALA - 147002

2. 1 INTRODUCTION
2 SUSTAINED RELEASE Vs CONTROLLED RELEASE
3 ADVANTAGES & DISADVANTAGES
4 TYPES
I. RATE-PREPROGRAMMED DDS
A POLYMER MEMBRANE PERMEATION CONTROLLED DDS
B POLYMER MATRIX- DIFFUSION CONTROLLED DDS
C MICRORESERVOIR- PARTITION CONTROLLED DDS
II. ACTIVATION- MODULATED DDS
A PHYSICAL MEANS
B CHEMICAL MEANS
C BIOCHAMICAL MEANS
III. FEEDBACK REGULATED DDS
A BIOEROSION- REGULATED DDS
B BIORESPONSIVE DDS
C SELF-REGULATING DDS
IV. SITE SPECIFIC DDS
5 REFERENCE

3. INTRODUCTION
• The conventional drug delivery systems are the primary pharmaceutical
products commonly seen in the prescription and over-the-counter drug
marketplace. This type of drug delivery system is known to provide a
prompt release of drug.
• To achieve as well as to maintain the drug concentration within the
therapeutically effective range needed for treatment, it is often necessary to
take this type of drug delivery system several times a day. This results in a
significant fluctuation in drag levels.

4. • Recently, several technical advancements have been made. They have
resulted in the development of new techniques for drug delivery. These
techniques are capable of controlling the:-
• Rate of drug delivery.
• Sustaining the duration of therapeutic action.
• Targeting the delivery of drug to a specific tissue.
These advancements have led to the development of several novel drug
delivery systems that could revolutionize the method of medication and
provide a number of therapeutic benefits.

5. SUSTAINED RELEASE Vs CONTROLLED RELEASE
SUSTAINED RELEASE
This term constantly used to
describe a pharmaceutical
dosage form formulated to
retard the release of a
therapeutically active agent such
that its appearance in the
systemic circulation is delayed
and/or prolonged and its plasma
profile is sustained in duration.
CONTROLLED RELEASE
It implies a predictability and
reproducibility in the drug
release kinetics, which means
that the release of drug at a rate
profile that is not only
predictable kinetically, but also
reproducible from one unit to
another.

6. SUSTAINED RELEASE CONTROLLED RELEASE
In this initial dose of drug is released
immediately and remaining maintenance
dose is released slowly to achieve prolonged
therapeutic level which is not constant.
This delivers drug at a predetermined rate for
a specified period of time.
Constitutes a dosage form that provides
medication over extended period of time.
Constitutes dosage form that maintains
constant drug levels in blood or tissues.
SRDF generally do not attain zero order
release kinetics.
Maintains constant drug levels in the blood
target tissue usually by releasing the drug in
a zero-order pattern, i.e., the drug release
over time irrespective of concentration.
Usually do not contain mechanism to
promote localization of the drug at active
site.
It contain methods to promote localization of
drug at active site.

7. ADVANTAGES
• Reduced frequency of dosing.
• Improved patient compliance.
• Reduced toxicity due to overdose.
• Reduces the fluctuations in peak plasma concentration.
• Nighttime dosing can be avoided.

8. DISADVANTAGE
• Decreased systemic availability in comparison to immediate release
conventional dosage form.
• Poor in vivo-in vitro correlation.
• Possibility of dose dumping.
• Retrieval of drug is difficult.
• Higher cost of formulation.

9. TYPES OF RATE-
CONTROLLED
DRUG DELIVERY
SYSTEMS
I. RATE-
PREPROGRAMME
D DRUG
DELIVERY
SYSTEMS
II.ACTIVATION-
MODULATED
DRUG DELIVER
SYSTEMS
III.FEEDBACK-
REGULATED
DRUG
DELIVERY
SYSTEMS
IV.SITE-
TARGETING
DRUG
DELIVERY
SYSTEMS

10. • In this system, the release of drug molecules from the delivery systems
has been pre-programmed at specific rate profiles.
• This was accomplished by system design, which controls the
MOLECULAR DIFFUSION of drug molecules in and/or across the barrier
medium within or surrounding the delivery system.
• Fick’s law of diffusion are often followed.
I. RATE- PREPROGRAMMED DRUG DELIVERY
SYSTEMS

11. Rate
preprogrammed
drug delivery system

12. These systems can be further classified as:-
A. Polymer membrane - permeation controlled systems
B. Polymer matrix – diffusion-controlled systems
C. Micro reservoir – partition-controlled systems

13. A. Polymer membrane - permeation controlled systems
• A drug formulation is totally or partially encapsulated within a drug reservoir
compartment.
• The drug release surface is covered by a rate controlling polymeric membrane
having a specific permeability.
• The drug reservoir may exist in solid, solution or suspension form.
• The polymeric membrane can be fabricated from nonporous(homogenous or
heterogeneous) or a micro porous (semipermeable) polymeric material.
• Encapsulation of drug formulation inside the reservoir compartment is done by,
 INJECTION MOLDING
 SPRAY COATING
 CAPSULATION
 MICROENCAPSULATION

14. Various shapes of
polymer membrane
permeation-controlled
drug delivery systems.

15. • The rate of drug release Q/t from this polymer membrane permeation-
controlled drug delivery system should be a constant value and is defined by
𝑄
𝑡
=¿
𝐾 𝑎
𝑚
𝐾 𝑚
𝑟
𝐷𝑑 𝐷𝑚
𝐾 𝑚
𝑟
𝐷𝑚 h𝑑
+
𝐾 𝑎
𝑚
𝐷𝑑 h𝑚
𝐶𝑅
𝐾 𝑚
𝑟
 Partition co-efficient of drug from reservoir to rate controlling membrane
𝐾 𝑎
𝑚
 Partition coefficient of drug from rate controlling
membrane to surrounding aqueous diffusion layer
𝐷𝑚  Diffusion co-efficient in rate controlling membrane having thickness
𝐷𝑑
𝐶𝑅
 Diffusion co-efficient in aqueous diffusion layer
having thickness
h𝑚
h𝑑
 Concentration of drug in reservoir compartment

16. • The rate of drug release is programmed by controlling the,
oPartition coefficient of drug molecule.
oDiffusivity of drug molecule.
oThickness of rate-controlling membrane.
EXAMPLE :-PROGESTASERT INTRA UTERINE DEVICE
(IUD)
• Drug reservoir is a suspension of progesterone crystals in silicone medical
fluid and is encapsulated in the vertical limb of T-shaped device walled by a
non-porous membrane of Ethylene vinyl acetate co-polymer.
• It is engineered to deliver natural progesterone continuously in the uterine
cavity.

17. PROGESTASERT INTRA
UTERINE DEVICE (IUD)
• Release rate- 65 mcg/day
for 1 year, in the uterine
cavity to achieve
contraception.

18. B. Polymer matrix – diffusion-controlled systems
• Drug reservoir is prepared by homogenously dispersing drug particles in a rate
controlling polymer matrix fabricated from either a lipophilic or hydrophilic
polymer.
• Drug dispersion in polymer matrix is achieve by,
Blending a therapeutic dose of
finely ground drug particles with
a liquid polymer or a highly
viscous base polymer, followed
by cross-linking of polymer
chains.
Mixing drug solids with a
rubbery polymer at an elevated
temperature and is molded to
form DDS.

19. (a) a lipophilic, non-
swellable polymer
matrix with a growing
thickness of the drug
depletion zone
(b) a hydrophilic,
swellable polymer
matrix with a growing
thickness of the drug-
depleted gel layer, which
resulted from drug
release from the drug-
dispersing polymer
matrix.

20. • The rate of drug release is time dependent for this system and is defined at a
steady state by,
=
• A = initial drug loading dose in polymer matrix.
• CR=drug solubility in polymer (drug reservoir conc. in system)
• DP = diffusivity of drug molecules in polymer matrix.
• The release of drug is controlled at a preprogrammed rate by controlling the
loading dose, polymer solubility of drug and diffusivity of drug in polymer
matrix.

21. EXAMPLE:- NITRO-DUR, A TRANSDERMAL DDS
• It is fabricated by first heating an aqueous solution of water-soluble polymer,
glycerol and polyvinyl alcohol.
• The temperature of solution is then gradually lowered, and nitroglycerine and
lactose triturate are dispersed just above the congealing temperature of
solution.
• The mixture is then solidified in mold at or below room temperature and then
sliced to form a medicated polymer disk.
• Dosage rate: 0.5 mcg / cm2
/ day onto an intact skin.
• Use: For the treatment of angina pectoris to provide a continuous transdermal
infusion of nitroglycerine.

22. CROSS-SECTIONAL
VIEW OF NITRO-DUR
SHOWING VARIOUS
STRUCTURAL
COMPONENTS.
Dosage rate: 0.5 mcg /
cm2
/day onto an intact
skin.

23. C. Micro reservoir partition- controlled drug delivery
systems.
• In this type drug reservoir is fabricated by micro dispersion of an aqueous
suspension of drug using a high energy dispersion technique in a
biocompatible polymer such as silicone elastomers, to form a homogenous
dispersion of many discrete microscopic drug reservoirs.
• Different shapes and sizes of drug delivery system devices can be fabricated from
this micro reservoir DDS by molding or extrusion.
• Depending on physicochemical properties of drug and the desired rate of drug
release rate, the device can be further coated with a layer of biocompatible
polymer to modify the mechanism and release rate.

24. The rate of drug release (dQ / dt) is defined by,
= nSp - 1
𝐾 𝑙
+
1
𝐾 𝑚
m = a/b
ratio of drug conc in bulk of elution solution over drug solubility in the
same medium.
a =
ratio of drug conc at the outer edge of the polymer coating membrane over
the drug solubility in same polymer.
b =
ratio of drug conc at the inner edge of interfacial barrier over the drug
solubility in the polymer matrix.
n =

25. Kl =
Kp
Km=partition coefficient for interfacial partitioning of drug from polymer
matrix to polymer coating membrane.
partition coefficient for interfacial partitioning of drug from liquid
compartments to polymer matrix.
partition coefficient for interfacial partitioning of drug from polymer
coating membrane to elution solution.
=
Dl = diffusivity of drug in liquid layer surrounding the drug particles.
DP = diffusivity of drug in polymer coating membrane enveloping polymer
matrix.

26. Dd = diffusivity of drug in hydrodynamic diffusion layer surrounding the
polymer coating membrane.
hl, hp, hd = thickness.
Sl = solubility of drug in liquid compartments.
Sp = solubility of drug in polymer matrix.
• Release of drug molecules from this type of CDDS can follow either
dissolution or matrix diffusion-controlled process depending on relative
magnitude of Sl and Sp.

27. EXAMPLE: TRANSDERMAL NITRO DISC SYSTEM
• The drug reservoir is formed by first preparing a suspension of nitroglycerine
and lactose triturate in an aqueous solution of 40% PEG 400 and dispersing it
homogenously with isopropyl palmitate, as dispersing agent, in a mixture of
viscous silicone elastomers by high energy mixing and then cross linking the
polymer chain by catalyst.
• It is then molded to form a solid medicated disk, on a drug-impermeable
metallic plastic laminate with surrounding adhesive rim, by injection molding
under instantaneous heating.
• Release rate: 0.5 mg / cm2
/ day , to treat ANGINA PECTORIS.

28. CROSS – SECTIONAL
VIEW OF NITRODISC.
Release rate: 0.5 mg /
cm2
/ day.

29. • In this system, the release of drug molecules from the delivery system is
activated by some:-
1. Physical means
2. Chemical means
3. Biological process
4. External energy
• The rate of drug release is then controlled by regulating the process applied
or energy input.
II. ACTIVATION MODULATED DRUG
DELIVERY SYSTEMS

30. ACTIVATION
MODULATED DDS

31. CLASSIFICATION (BASED ON NATURE OF PROCESS APPLIED OR TYPE OF
ENERGY USED)
1 PHYSICAL MEAN A. Osmotic pressure activated DDS
B. Hydrodynamic pressure activated DDS
C. Vapour pressure 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

32. PHYSICAL MEANS

33. A. OSMOTIC PRESSURE ACTIVATED DDS
• Osmotic drug delivery uses the osmotic pressure for controlled delivery of drugs
by using osmogens.
• These system can be used for both route of administration i.e, oral and parenteral.
• Osmogens: Drug itself may act as an osmogen and shows great aqueous solubility
(e.g. potassium chloride Pump). Osmogens are fundamental ingredient of the
Osmotic formulation. They include inorganic salts and carbohydrates. Generally,
combination of osmogen is utilized to achieve optimum osmotic pressure inside
the framework. For the selection of osmogen, the two most critical properties to be
considered are osmotic movement and aqueous solubility.

34. Osmotic agents are classified as:-
(i) Inorganic water-soluble osmogenes: Magnesium sulphate, Sodium chloride,
Sodium sulphate, Potassium chloride, Sodium bicarbonate.
(ii) Organic polymeric osmogens: Sodium CMC, HPMC, HEMC.
(iii) Organic water soluble osmogens: Sorbitol, Mannitol.
• In this system, drug reservoir can be solution or a solid formulation and is
contained within a semi-permeable housing with controlled water permeability.
• The drug is activated to release in a solution form, at a constant rate through a
special delivery orifice with Pore size: 0.4 µm.
• The rate of drug release is modulated by controlling osmotic pressure
gradient.

35. • The intrinsic rate of drug release Q / t is defined by,
• Pw  Water permeability
• Am  Effective surface area
• hm  Thickness of semipermeable housing
• Sd  Aqueous solubility of solid drug
• 𝞹s  Osmotic pressure of drug delivery system
• 𝞹e  Osmotic pressure of environment
For a solution formulation, =
For a solid formulation, = Sd

36. ADVANTAGES
• Drug release from osmotic pumps is independent of the gastric pH and hydrodynamic
Condition of the body.
• Higher release rates are possible from osmotic systems than with conventional diffusion-
based drug delivery systems.
• Drug release from the osmotic systems is minimally affected by the presence of food.
• Improved patient compliance with reduced dosing frequency.
• Increased safety margin of high potency drugs.
• It is possible to attain better release rates than those obtained with conventional

37. DISADVANTAGES
• If the coating process is not well controlled there is a risk of film defects, which
results in dose dumping.
• Hole Size is critical in case of elementary osmotic system.
• Retrieval of therapy is not possible in the case of unexpected adverse event.
• Rapid development of tolerance
• Hypersensitivity reaction may occur after implantation.
• Integrity and consistency of the coating process is not well controlled there is
dose dumping. The film beads or particles must be instigated to combine into a
film with steady properties.

38. CLASSIFICATION OF OSMOTIC DDS
IMPLANTABLE OSMOTIC DDS ORAL OSMOTIC DDS
1. Alzet osmotic pump 1. Elementary osmotic pump
2. Higuchi leeper osmotic pump 2. Modified osmotic pump
3. Higuchi theeuwes osmotic pump 3. Multi chamber osmotic pump
4 Rose nelson pump 4. Controlled porosity osmotic pump
5. Multi particulate delayed release system
6. Monolithic osmotic system

39. EXAMPLE: ALZET OSMOTIC PUMP
• In the implantable or insertable Alzet osmotic pump the drug reservoir, which is
normally a solution formulation, is contained within a collapsible, impermeable
polyester bag.
• The external surface is coated with a layer of osmotically active salt (sodium
chloride).
• This reservoir compartment is then completely sealed inside a rigid housing
walled with a semipermeable membrane.
• At the implantation site the water component in the tissue fluid penetrates
through the semi-permeable housing to dissolve the osmotically active salt.

40. • This creates an osmotic pressure in the narrow spacing between
the flexible reservoir compartment wall and the rigid
semipermeable housing.
• Under the osmotic pressure the reservoir compartment is forced
to reduce its volume and drug solution is delivered at a
controlled rate.
• The drug concentration in the solution, different doses of drug can
be delivered at a constant rate for a period of 1-4 weeks.

41. ALZET OSMOTIC
PUMP

42. EXAMPLE:- ELEMENTARY OSMOTIC PUMP
Composition: It contains an active agent having a suitable osmotic pressure. it
fabricate as a tablet coated with semi permeable membrane.
Mechanism: Imbibes water through the semipermeable membrane because of
osmotic pressure gradient and forms the saturated medication solution inside
the device. This increases the hydrostatic pressure inside the tablet forces the
saturated drug solution through the hole present in film.
Advantages: suitable for delivery of drug having moderate water solubility.

43. THE ELEMENTARY
OSMOTIC PUMP

44. B. HYDRODYNAMIC PRESSURE ACTIVATED DDS
• This system is fabricated by enclosing a collapsible, impermeable container,
which contains a liquid drug formulation to form a drug reservoir, inside a rigid
shape retaining housing.
• A composite laminate of an absorbent layer and a swellable, hydrophilic polymer
layer (poly hydroxy alkyl methacrylate) is sandwiched between drug reservoir and
the housing.
• In GIT, the laminate absorbs GI fluid through annular opening at the lower end of
the housing and swells generating hydrodynamic pressure which forces the drug
reservoir compartment to reduce in volume and causes the liquid drug formulation
to release through the delivery orifice.

45. HYDRODYNAMIC
PRESSURE
ACTIVATED DDS
A CROSS-SECTIONAL
VIEW

46. • The rate of drug delivery through the delivery orifice can be defined as,
= (𝞠s - 𝞠e)
Pf  Fluid permeability
Am  Effective surface area
hm  Thickness of the wall with annular openings
(𝞠s - 𝞠e)  Difference in hydrodynamic pressure of system( s) and
𝞠
environment( e)
𝞠

47. C. VAPOUR PRESSURE ACTIVATED DDS
• Vapor pressure has also been discovered as a potential energy source to activate
the delivery of therapeutic agents.
• In this type of system, the drug reservoir(which also exist as a solution
formulation) is contained inside the infusion compartment.
• It is physically separated from the pumping compartment by a freely movable
partition.
• The pumping compartment contains a fluorocarbon fluid that vaporizes at body
temperature at the implantation site and creates a vapor pressure.
• Under the vapor pressure created the partition moves upward.

48. • This forces the drug solution in the infusion compartment to be delivered
through a series of flow regulator and delivery cannula into blood circulation at
a constant flow rate.
• The rate of drug delivery Q / t is defined by,
=
d  Inner diameter of delivery cannula.
l  Inner length of delivery cannula.
Ps-Pe  Difference between vapour pressures at pumping compartment and
implantation site.
𝞵  Viscosity of the formulation used.

49. • Release of drug is activated by vapor pressure and controlled at a rate
determined by differential vapor pressure, formulation viscosity and size
of delivery cannula.
EXAMPLE: INFUSAID
Development of implantable infusion pump (infusaid) for constant infusion of,
1. HEPARIN – in anticoagulation treatment
2. INSULIN – in anti-diabetic medication
3. MORPHINE – in patients with intense pain of terminal cancer

50. A VAPOUR
PRESSURE –
ACTIVATED DDS
1.flow regulator,
2.silicone polymer coating,
3.partition,
4.pumping compartment,
5.infusate compartment,
6.fluorocarbon fluid filling tube,
7.filter assembly,
8.inlet septum for percutaneous
refill of infuscate,
9.needle stop

51. C. MECHANICALLY ACTIVATED DRUG
DELIVERY SYSTEMS
1. The force and duration of activation applied
2. The solution volume in the container.
• In this type of activation-controlled drug delivery system, the drug reservoir
is a solution formulation retained in a container equipped with a
mechanically activated pumping system.
• A measured dose of drug formulation is reproducibly delivered into a body
cavity.
• The volume of solution delivered is controllable as a small as 10-100µl, and
is independent of,

52. EG: METERED DOSE INHALER
• For the intranasal administration of a precision dose of,
1. LHRH- Leutinizing Hormone Releasing Hormone(BUSERELIN)
2. Bronchodilators - Salbutamol
3. Corticosteroids - Beclomethasone
4. Immune modulators - Cyclosporine
• Advantage – Avoidance of first pass metabolism

53. PUMPING SYSTEM
OF METERED
DOSE INHALER
A CROSS-SECTIONAL VIEW.

54. E. MAGNETICALLY ACTIVATED DRUG DELIVERY SYSTEM
• In this type of system, the drug reservoir is a dispersion of peptide or protein
powders in a polymer matrix from which macromolecular drug can be delivered at
a relatively slow rate.
• Magnetic drug delivery means the specific delivery of therapeutic agents to their
desired target area using magnetic field.
• A sub-dermally implantable, magnetically activated drug delivery device is
fabricated by first positioning a tiny magnet ring in the core of a hemispherical
drug-dispersing polymer matrix and then coating its external surface with a drug
impermeable polymer such as ethylene-vinyl acetate copolymer or silicone
elastomers, except one cavity at the center of flat surface.

55. • This uncoated cavity is positioned directly above the magnet ring, which
permits a peptide drug to be released.
• It is used to deliver protein drugs, such as bovine serum albumin, at a low
basal rate, by a simple diffusion process under non triggering conditions.
• As the magnet is activated to vibrate by an external electromagnetic field, the
drug molecules are delivered at a much higher rate.

56. HEMISPHERIC
MAGNETICALLY
ACTIVATED DDS

57. F. SONOPHERESIS ACTIVATED DRUG DELIVERY
SYSTEMS
• This type of DDS utilizes ultrasonic energy to activate the delivery of drugs
from a polymeric drug delivery device.
• The system can be fabricated from either a non-degradable polymer such as
ethylene-vinyl acetate copolymer or a bio erodible polymer such as poly [bis
(p-carboxy phenoxy) alkane anhydride.

58. SONOPHORESIS
ACTIVATED DRUG
DELIVERY
OF MANNITOL- IN
RAT INTACT SKIN

59. G. IONTOPHORESIS ACTIVATED DRUG
DELIVERY SYSTEMS
• This type of system uses the electrical current to activate and to modulate the
diffusion of a charged drug molecule, across a biological membrane like the
skin, in a manner like passive diffusion under a concentration gradient, but at
a much-facilitated rate.
• The iontophoresis- facilitated skin permeation rate of a charged molecule i
consists of 3 components and is expressed by,

60. Jp
= PASSIVE SKIN PERMEATION FLUX  Ks Ds
Je
= ELECTRICAL CURRENT DRIVEN PERMEATION FLUX  Ci
Jc
= CONVECTIVE FLOW DRIVEN SKIN PERMEATION FLUX  K Cs Id
Ji
isp
= Jp
+ Je
+ Jc

61. Ks = partition coefficient for interfacial partitioning from donor solution to stratum corneum.
Ds = diffusivity across the skin.
Di = diffusivity of ionic species i in the skin.
Ci = donor concentration of ionic species i the skin.
Cs = concentration in skin tissues.
dE/hs = electrical potential gradient across skin.
dC/hs = concentration gradient across skin.
Z i= electrical valence of ionic species i.
Id = current density applied.
F = faraday constant.
K = proportionality constant
T = absolute temperature

62. EXAMPLE:-
Phoresor by motion control to facilitate the percutaneous penetration of anti-
inflammatory drugs to surface tissues.
Example:-dexamethasone sodium phosphate
DEVELOPMENT:
• TPIS - Transdermal Periodic Iontotherapeutic System
• Capable of delivering pulse direct current in a periodic manner which is
physiologically acceptable with a special combination of waveform,
intensity, frequency and on/off ration.
• E.g. For proteineous drugs  INSULIN.

63. TPIS- AN
IONTOPHORESIS
ACTIVATED DRUG
DELIVERY SYSTEM

64. H. HYDRATION ACTIVATED DRUG
DELIVERY SYSTEM
• This type of system depends on hydration induced swelling process
to activate the release of drug.
• The drug reservoir is homogeneously dispersed in a swellable polymer
matrix fabricated from hydrophilic polymer.
• The release of drug is controlled by the rate of swelling of polymer
matrix.

65. EXAMPLE: VALRELEASE TABLETS
• It is prepared by granulation of homogenous dispersion of Valium (a
tranquilizer) in hydrocolloid and excipients.
• The granules are compressed to form tablets.
• After oral intake, the hydrocolloid in tablet absorbs GI fluid and forms a
colloidal gel that starts from the tablet surface and grows inwards.
• The release of Valium molecules is then controlled by matrix diffusion through
this gel barrier.
• The tablet remain buoyant in the stomach as a result of the density difference

66. A HYDRATION
ACTIVATED SYSTEM
HYDRATION INDUCED
FORMATION OF
COLLOIDAL GEL
BARRIER(VALRELEASE
TABLET)

67. CHEMICAL MEANS

68. A. pH ACTIVATED DRUG DELIVERY
SYSTEMS
• This type of DDS permits the delivery of a drug only in the region with a
selected pH range.
• It is fabricated by coating the drug containing core with a pH sensitive
polymer combination.
• Gastric fluid labile drug is protected by encapsulating it inside a polymer
membrane that resists the degradative action of gastric pH, such as
combination of ethyl cellulose and hydroxy methylcellulose phthalate.

69. • In stomach, coating membrane resists the action of gastric fluid, and the drug
molecules are thus protected from acid degradation.
• After gastric emptying the drug delivery system travels to small intestine and
intestinal fluid will activate the erosion of intestinal fluid soluble hydroxy
methylcellulose phthalate component from coating membrane.
• This leaves a micro porous membrane of intestinal fluid insoluble polymer of
ethyl cellulose, which controls the release of drug from the core tablet.
• The drug solute is thus delivered at a controlled manner in intestine by
combination of dissolution and pore-channel diffusion.
• By adjusting the ratio of intestinal fluid soluble polymer to intestinal fluid
insoluble polymer, the membrane permeability of drug can be regulated as
desired.

70. pH DEPENDENT
FORMATION OF
MICROPOROUS
MEMBRANE IN INTESTINE

71. B. ION – ACTIVATED DRUG DELIVERY
SYSTEMS
• An ionic or charged drug can be delivered by ion-activated DDS.
• It is prepared by first complexing an ionic drug with an ion exchange resin
containing a suitable counter ion (Cationic drug with SO3
-
resin, Anionic drug
with N(CH3)3
+
resin).
• The granules of drug-resin complex are first treated with an impregnating
agent, PEG-4000, to reduce the rate of swelling in an aqueous environment
and then coated by air-suspension coating, with a water insoluble polymer
such as ethyl cellulose.

72. • 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 electrolyte medium, such as gastric fluid, ions diffuse into system, react with
drug-resin complex and trigger the release of ionic drug.
• This system is exemplified by the development of Pennkinetic (by Pennwalt
Pharmaceuticals) which permits the formulation of liquid suspension dosage form
with sustained release drug properties for oral administration.
• Since GI fluid regularly maintains a constant level of ions, i.e., constant ionic
strength, the delivery of drug from this system can be maintained at a constant
rate relatively.

73. ION ACTIVATED DRUG
DELIVERY SYSTEM

74. C. HYDROLYSIS ACTIVATED DRUG
DELIVERY SYSTEM
• This type of activation-controlled drug delivery system depends on hydrolysis
process to activate the release of drug molecules.
• Here, drug reservoir is either encapsulated in microcapsules or homogeneously
dispersed in microspheres or nanoparticles for injection.
• It can also be fabricated as an implantable device.

75. • All these systems are prepared by bio erodible polymer such as co(lactic-
glycolic) polymer, poly ortho ester or poly anhydride.
• The release of drug from polymer matrix is activated by hydrolysis induced
degradation of polymer chains and controlled by the rate of polymer
degradation.
• EXAMPLE: Development of LHRH releasing biodegradable subdermal
implant designed to deliver goserelin (synthetic LHRH analogue) for once-a-
month treatment of prostate cancer.

76. AMINO ACID SEQUENCE OF
GOSERELIN, A SYNTHETIC
LHRH, AND THE EFFECT OF
SUBCUTANEOUS CONTROLLED
RELEASE OF GOSERELIN FROM
THE BIODEGRADABLE POLY
SUBDERMAL IMPLANT

77. BIOCHEMICAL MEANS

78. A. ENZYME- ACTIVATED DRUG DELIVERY
SYSTEMS
• This type of activation-controlled drug delivery system depends on enzymatic
process to activate the release of drug.
• In this system the drug reservoir is either physically entrapped in
microspheres or chemically bound to polymer chains from biopolymer, such
as albumin or polypeptides.
• The release of drug is activated by enzymatic hydrolysis of biopolymers by a
specific enzyme in the target tissue.
EXAMPLE: Development of albumin microspheres that release 5-flurouracil
in a controlled manner by protease activated biodegradation.

79. • The release of drug from delivery system is activated by a triggering agent
such as a biochemical substance, in the body and regulated by its
concentration via some feedback mechanism.
• Rate of drug release is controlled by the concentration of triggering agent
detected by a sensor in the feedback regulated mechanisms.
III. FEEDBACK REGULATED DRUG DELIVERY
SYSTEM

80. FEEDBACK
REGULATED DRUG
DELIVERY SYSTEM

81. Feedback regulated drug delivery concept is applied to
A. BIOEROSION – REGULATED DDS
B. BIORESPONSIVE – DDS
C. SELF – REGULATING DDS

82. A. BIOEROSION – REGULATED DRUG
DELIVERY SYSTEMS
• The system consist of drug-dispersed bioerodable matrix fabricated from poly
(vinyl methyl ether) half-ester, which is coated with a layer of immobilized
Urease, in a solution with neutral pH polymer erodes very slowly.
• In presence of urea, Urease at the surface of drug delivery system metabolizes
urea to ammonia.
• This causes pH to increase and a rapid degradation of polymer matrix as well as
the release of drug molecules.

83. BIOEROSION
REGULATED
DELIVERY OF
HYDROCORTISON- A
FEEDBACK
REGULATED SYSTEM

84. C. BIORESPONSIVE DRUG DELIVERY
SYSTEM
• In this system, the drug reservoir is contained in a device enclosed by a
Bio responsive polymeric membrane whose drug permeability is
controlled by the concentration of biochemical agent in the tissue where
the system is located.
• Development of glucose-triggered insulin delivery system in which the
insulin reservoir is encapsulated within a hydrogel membrane having
pendant-NR2 groups.

85. • In alkaline solution - NR2 groups are neutral, and membrane is unswollen and
impermeable to insulin.
• As glucose, a triggering agent penetrates the membrane, it is oxidized
enzymatically by glucose oxidase entrapped in membrane to form gluconic acid.
• The -NR2 groups are to protonated to form –NR2H+
, and the hydrogel membrane
then becomes swollen and permeable to insulin molecules.
• The amount of insulin delivered is thus Bio responsive to the concentration of
glucose penetrating the insulin delivery system.

86. A FEEDBACK-
REGULATED DRUG
DELIVERY SYSTEM
CROSS-SECTIONAL VIEW
OF BIORESPOSIVE
INSULIN DELIVERY

87. C. SELF REGULATING DRUG DELIVERY
SYSTEMS
• This type of feedback regulated drug delivery system depends on a
reversible and competitive binding mechanism to activate and to regulate
the release of drug.
• In this system the drug reservoir is a drug complex encapsulated in a
semipermeable polymeric membrane.
• The release of drug from the delivery system is activated by the membrane
permeation of a biochemical agent from the tissue in which the system is
located.

88. • Reversible binding of sugar molecules by lectin in the design of self-regulating
drug delivery system. It first involves preparation of biologically active insulin
derivatives in which insulin is coupled with a sugar (maltose) and this into an
insulin-sugar-lectin complex.
• The complex is then encapsulated within a semi permeable 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.
• The released insulin-sugar derivatives then diffuse out of the device, and the
amount of insulin-sugar derivatives released depends on the glucose
concentration. Thus, a self-regulating drug delivery is achieved.

89. SELF-REGULATING
INSULIN DELIVERY
SYSTEMS

90. • Site specific or Targeted drug delivery system is a special form of DDS,
where drug is selectively targeted or delivered only to its site of action or
absorption and not to the non-target organs, tissues and cells.
• The release of drug is activated by the membrane permeation of a
biological agent from the tissue in which the DDS is located.
IV. SITE SPECIFICDRUG DELIVERY
SYSTEM

91. CARRIERS OR MARKERS
• Targeted drug delivery can be achieved by using carrier system. Carrier is one
of the special molecule or system essentially required for effective
transportation of loaded drug up to the preselected sites.
• They are engineered vectors, which retain drug inside or onto them either via
encapsulation and/or via spacer moiety and deliver it into vicinity of target
cell.
• Example: polymers, microcapsules, microparticles, lipoproteins, liposomes
and micelles.

92. SITE SPECIFIC DRUG
DELIVERY SYSTEM

93. EXAMPLE: THE MECHANISM OF REVERSIBLE BINDING OF
SUGAR MOLECULES BY LECTIN
• It involves preparation of biologically active insulin derivatives in
which insulin is coupled with a sugar(E.g. MALTOSE) to form insulin
– sugar – lectin complex.
• This complex is encapsulated within a semipermeable membrane.
• Blood glucose diffuse into the device and competitively binds at the
sugar binding sites in lectin molecules.

94. • This activated the release of bound insulin – sugar derivatives.
• The amount of insulin – sugar derivatives released depends on the blood
glucose concentration, i.e., a self regulatory system.
• Drawback: Release of insulin from device in non-linear in response to
the changes in glucose level.

95. The drug may be delivered,
• To the capillary bed of the active sites.
• To the specific type of cell or even an intracellular region.
Ex: Tumor cells but not to normal cells.
• To a specific organ or tissue by complexation with the
carrier that recognizes the target.

96. THANK YOU