This document discusses different types of rate-controlled drug delivery systems. It begins by distinguishing between sustained release and controlled release systems. It then describes four main classifications of rate-controlled delivery: pre-programmed, activation-modulated, feedback-regulated, and site-targeting systems. Within pre-programmed systems, it outlines polymer membrane permeation, polymer matrix diffusion, and microreservoir partition controlled systems. It provides examples like transdermal patches. Activation modulated systems are triggered physically, chemically, or biochemically, like osmotic pumps. Feedback regulated systems sense biochemical triggers to control drug release. The document covers many controlled release mechanisms and technologies.

1. PRESENTED BY :
R.ARULKUMAR., B. DHARANI PRIYA
M.PHARMACY- 1ST YEAR
KMCH COLLEGE OF PHARMACY
RATE-CONTROLLED DRUG
DELIVERY SYSTEM
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2. INTRODUCTION:
 Sustained release, sustained action, controlled release, extended
action, timed release dosage forms are the terms used to identify drug
delivery systems that are designed to achieve a prolonged therapeutic
effect by continuously releasing medication over an extended period
of time after the administration of single dose.
 The term “Controlled release” has become associated with those
systems can include the maintenance of drug levels within a
predetermined rate for a specified period of time
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3. But, there are some confusion in terminology between "Controlled
release” & “Sustained release”
Sustained Release :
Sustained-release systems include any drug-delivery system that
achieves slow release of drug over an extended period of time.
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4. Controlled Release :
In this type of dosage forms it provides a prolonged duration
of drug release with predictability and reproducibility of drug
release kinetics. In this case, the rate of drug absorption is
equal to the rate of drug removal from body.
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5. 1/30/2020 5DEPARTMENT OF PHARMACEUTICS

6. Advantages:
 Less fluctuation in drug blood levels.
 Frequency reduction in dosing.
 Improved patient convenience & compliance.
 Increased safety margin of the high potency drugs.
 Reduction in total health care cost.
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7. Disadvantages:
 Decreased systemic availability in comparison to immediate
release conventional dosage forms.
 Poor in vivo – in vitro correlation.
 Possibility of dose dumping.
 Retrieval of drug is difficult.
 Higher cost of formulation.
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8. Classification Of Rate Controlled Drug
Delivery System
 Rate-preprogrammed drug delivery systems
 Activation-modulated drug delivery systems
 Feedback-regulated drug delivery systems
 Site- targeting drug delivery systems
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9. RATE PREPROGRAMMED DRUG DELIVERY
SYSTEM
In this group of controlled release drug delivery systems, the
release of the drug molecules from the delivery systems has been
preprogrammed at specific rate profiles. Fick’s law of diffusion are
often followed.
These systems can be further classified as follows:
1.Polymer membrane permeation- controlled drug delivery systems.
2. Polymer matrix diffusion- controlled drug delivery systems.
3. Microreservoir partition-controlled drug delivery systems.
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10. RATE PREPROGRAMMED DRUG DELIVERY SYSTEM
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11. POLYMER MEMBRANE PERMEATION
In this type of preprogrammed drug delivery systems, a drug
formulation is totally or partially encapsulated within a drug
reservoir compartment.
Different shapes and sizes of drug delivery systems can be
fabricated.
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12. POLYMER MEMBRANE PERMEATION
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13.  The rate of the drug release Q/t from this polymer membrane
permeation-controlled drug delivery system should be a constant
value and is defined by:
Where, Km/r and Ka/m = partition coefficients for the
interfacial partitioning drug molecules .
Dm and Dd = diffusion coefficients in the rate-controlling
membrane (with thickness hm) and in the aqueous diffusion layer
 CR is the drug concentration in resorvoir compartment.
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14. Representatives of this type of drug delivery system are as
follows
progestasert IUD:
It is an intrauterine device, the drug reservoir is a suspension of
progesterone crystals in silicone medical fluid and is encapsulated in
the vertical limb of a T-shaped device walled by a non porous
membrane of ethylene-vinyl
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15. Norplantsubdermal implant:
It is fabricated from nonporous silicone medical- grade tubing(with
both ends sealed with silicone medical grade adhesive)to
encapsulate either levonorgestrel crystals alone or a solid
dispersion of levonorgestrel in silicone elastomer matrix.
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16. Transderm-nitro
Is a transdermal therapeutic system in which the drug
reservoir, a dispersion of nitroglycerin-lactose triturate in silicone
medical fluid, is encapsulated in a thin ellipsoidal patch.
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17. POLYMER MATRIX DIFFUSION SYSTEM
 In this type of preprogrammed drug delivery system the drug
reservoir is prepared by homogenously dispersing drug particles in
a rate-controlling polymer matrix fabricated either a lipophilic or
hydrophilic polymer.
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18. 1/30/2020 18DEPARTMENT OF PHARMACEUTICS

19.  Representatives of this type of drug delivery system are as
follows:
 Nitro- dur: it is a transdermal drug delivery system.
 Fabricated by first heating an aqueous solution of water soluble
polymer, glycerol and PVA.
 The temperature of the solution is gradually lowered and
nitroglycerin and lactose triturate is dispersed just above the
congealing temperature of the solution.
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20. MICRORESERVOIR PARTITION
 In this type of preprogrammed drug delivery system the drug
reservoir is fabricated by microdispersion 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, unleachable, microscopic drug
reservoirs.
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21. Representatives of this type of drug delivery systems is as
follows:
Transdermal nitrodisc system:
 In the transdermal nitrodisc system the drug reservoir is formed
first preparing suspension of nitroglycerin and lactose triturate in an
aqueous solution of 40% polyethylene glycol 400.
 Dispersing the above mixture homogenously with isopropyl
palmitate ( dispersing agent) in a mixture of viscous silicone
elastomer.
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22.  The resultant drug polymer dispersion is then molded to form a
solid medicated disk in situ on a drug-impermeable metallic plastic
laminate, with surrounding adhesive film by injection molding
under instantaneous heating.
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23. 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.
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24. ACTIVATION MODULATED DRUG DELIVERY SYSTEM
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25.  It can be classified into
 PHYSICAL MEANS
 Osmotic pressure activated DDS
 Hydrodynamic pressure activated DDS
 Vapour pressure activated DDS
 Mechanically activated DDS
 Sonophoresis activated DDS
 Iontophoresis activated DDS
 Hydration activated DDS
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26. Chemical means
 pH activated DDS
 Ion activated DDS
 Hydrolysis activated DDS
Biochemical means
 Enzyme activated DDS
 Biochemical activated DDS
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27. MECHANICALLY ACTIVATED DDS
 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 as10-
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
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28. MECHANICALLY ACTIVATED DDS
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29. pH ACTIVATED DRUG DELIVERY SYSTEM
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.
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30. pH ACTIVATED DRUG DELIVERY SYSTEM
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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.
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32. 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
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33. OSMOTIC ACTIVATED DRUG DELIVERY SYSTEM
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34.  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.
 Prolonged therapeutic effect with uniform blood
concentration.
 Inexpensive and their production scale up is easy.
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35. 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
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36. MATERIALS USED IN FORMULATION OF OSMOTIC
SYSTEM
 Semipermeable membrane
 Hydrophilic and hydrophobic polymers
 Wicking agents
 Solubilizing agents
 Osmogens
 Surfactants
 coating solvents
 Plasticizers
 Pore forming agents
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37. ENZYME ACTIVATED DRUG DELIVERY SYSTEM
 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
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38. FEEDBACK REGULATRORY 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.
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39. It isclassifiedin to thefollowing:
1) Bioerosion-regulated drug delivery systems
2) Bioresponsive drug delivery systems
3) Self regulating drug delivery systems
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40. BIOEROSION REGULATED
 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
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41. 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.
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42. BIORESPONSIVE
 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.
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43. SELF REGULATING
 Typical example of this bioresponsive DDS is the development of a
glucose-triggered insulin delivery system
 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.
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44. SITE- TARGETING DRUG DELIVERY
SYSTEMS:
Site-specific and receptor targeting refer to targeting of a drug
directly to a certain biological location. In the case of site-specific
release, the target is adjacent to or in the diseased organ or tissue.
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45. References:
 Novel drug delivery system- Chien. Pg no. 1-132.
 Biopharmaceutics & pharmacokinetics- Brahmankar. Pg no. 335 – 370.
 Fundamentals of controlled release drug delivery- Robinson. Pg no. 482 –
508.
 Novel drug delivery systems by Yie W. Chein. Pg no 1 – 37
 Osmotic drug delivery systems
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407637
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