This document discusses different approaches to controlled drug delivery systems. It begins by distinguishing between sustained release and controlled release systems. It then classifies controlled drug delivery systems into four main categories: rate-programmed delivery systems, activation-modulated systems, feedback-regulated systems, and targeted/localized systems. Specific examples of each type of system are provided, such as osmotic pressure-activated systems, pH-activated coatings, and glucose-responsive insulin pumps. The goal of these approaches is to control the rate and location of drug release in the body.

1. Approaches to controlled drug
delivery system
Presented By:-
NIVEDITHA G
1st M pharm
Dept. of pharmaceutics
NARGUND COLLEGE OF PHARMACY

2. Contents:
 Introduction
 Terminology
 Classification
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3. Introduction
 Several techniques has been developed.
 Because of advancement, NDDS got revolunized
better therapeutic benefits.
 Confusion between “Sustained release” and
“Controlled release”
 Sustained Release: Dosage form formulated to retard
release of the agent, such as delayed or prolong
duration.
 Controlled Release: Meaning goes beyond sustained
release.
 Release proceeds at rate profile and release of drug
is constant.
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4. Terminology
 Necessary to provide terminology.
 System attempts to control drug conc. In the targeted tissue or
cell.
 In sustained release, prolong therapeutic blood or tissue level of
drug but not control.
 Attempts to :
 Sustain drug action at predetermined rate
 Localize drug action by spatial placement of CRS
( rate controlled)
 Target drug action using carrier and chemical derivatization.
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5.  Plasma drug concentration profile:-
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6. Classification:
 Rate programmed DDS
 Activation modulated DDS
 Feedback regulated DDS
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7. Four classes of controlled drug delivery system:-
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8. Rate-Programmed DDS
 Release of drug from the system has been pre-
programmed at specific rate profile.
 Classification:
 Polymer membrane permeation CDDS
 Polymer matrix diffusion CDDS
 Microreservoir Partition CDDS
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9. Polymer membrane permeation- CDDS
 Drug release surface covered with rate controlling
polymeric membrane.
 Polymeric membrane non porous polymeric
materials or semi permeable membrane.
 Shapes Sphere, Cylinder, Sheet
 Drug release controlled at preprogrammed rate by
controlling partition coefficient, diffusivity of drug,
and thickness of membrane.
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10. Polymer matrix diffusion- CDDS
 Preprogrammed DDS
 Drug molecules polymer matrix ( lipophilic or
hydrophilic)
 Also by Tech Solvent Eva. at elevated temp.
 Solvent Evaporation ( Drug + Polymer common
solvent.)
 Release of drug controlled by loading dose, polymer
solubility of drug, diffusivity drug in polymer.
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11. Micro reservoir partition- CDDS
 Preprogrammed DDS
 Drug reservoir fabricated by micro dispersion of aq.
Suspension of drug in biocompatible polymer by
using high energy dispersion e.g. silico-elastomers.
 Shapes Molding or extrusion.
 To modify release, device further coated.
 Rate of release follows dissolution or matrix diffusion
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12. Activation modulated DDS
 Release of drug from the system activated by some
physical, chemical, biological processes.
 Rate of release controlled by regulating the
processes or applied energy.
 Classification:
 A) Physical mean B) Chemical mean C) Bio
chemical mean.
 Physical mean: osmotic pressure, hydrodynamic
pressure, vapour pressure, mechanically activated,
hydration activated.
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13.  Chemical mean: PH activated , Ion activated,
Hydrolysis activated.
 Biochemical mean: Enzyme activated, Hydration
activated
 A) Osmotic Pressure activated- DDS:
 Depends upon osmotic pressure to activate release.
 Rate of release controlled by osmotic gradient.
 Can also be controlled by water permeability,
effective surface area of semi permeable housing.
 E.g. Alzet osmotic pump
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14.  Alzet osmotic pump:-
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15.  B) Hydrodynamic pressure activated- DDS
 Depends upon hydrodynamic pressure
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16.  C) Vapour pressure activated- DDS
 Depends upon vapour pressure.
 Pumping compartment contain fluorocarbon fluid
which vaporized at body temp at implantation site
and create vapour pressure.
 Pressure moves partition upwards and this force
causes the delivery of drug solution.
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17.  D) Mechanically activated- DDS
 Depends upon mechanical pressure.
 Measured qty of drug formulation delivered to body
cavity e.g. nose through spray
 Volume of solution is controllable (10- 100 ư)
 E.g. metered dose nebuliser.
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18.  Mechanically activated drug delivery system
(Mechanical pump)
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19.  E) Hydration activated- DDS
 Depends upon hydration- induced swelling process to
activate the release.
 Drug reservoir swell able polymer matrix(
hydrophilic)
 Release of drug can be controlled by rate of swelling
of polymer matrix.
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20.  F) PH activated- DDS
 Delivery of drug only in region of specific PH ranges.
 Drug containing core fabricated with PH sensitive
polymer combination.
 E.g. in GIT coating membrane resist action of gastric
fluid & protect gastric degradation
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21.  G) Ion activated- DDS
 Ionic or charged drug can only be delivered by this system.
 System preparation: complexing ionic drugs.
 ( complex of cationic or complex of anionic + resin having
N(CH3)3 groups= system)
 ( Granules of system impregnating agent (e.g. polyethylene
glycol 4000) reduce rate of swelling and then coated by water
insoluble membrane. ( ethylene cellulose).
 Membrane works as rate controlling barrier to modulate influx of
ions as well as release of drug from system
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22.  H) Hydrolysis activated DDS
 Depends on hydrolysis to activate the release.
 Can be fabricated as implantable device.
 System prepared from bio-degradable polymers only
e.g. poly (lactic-glycolic), poly (anhydride)
 Release of drug achieved by hydrolysis induced
degradation of polymer chain.
 Rate of release controlled by rate of polymer
degradation.
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23.  I) Enzyme activated DDS
 Need enzymatic processes to activate release of
drug.
 System activates by the enzymatic hydrolysis of bio
polymers by specific enzyme in tissue.
 E.g. development of albumin micro sphere that
release 5-flurouracil in controlled manner by protease
activated biodegradation.
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24. Feedback regulated DDS
 Release of drug activates by triggering agent e.g.
biochemical sub. in the body and also regulated by its
concentration via some feedback mechanism.
 Rate of release controlled by conc. of triggering
agent.
 Some feedback regulated systems:
 Bioerosion - regulated DDS
 Bioresponsive - regulated DDS
 Self regulating DDS
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25.  Bioerosion regulated DDS
 Feedback regulated DDS concept applied.
 Consist of drug dispersed bio- erodible matrix ( poly-
vinyl methyl ether)
 Coated with immobilized urease.
 In neutral PH polymer erodes very slowly.
 In presence of urea urease present at surface of
system – metabolized urea to ammonia.
 Causes increase in PH and rapid degradation of
polymer matrix and also release of drug molecules.
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26.  Bio responsive DDS
 Feedback regulated concept.
 Device having drug reservoir enclosed by
bioresponsive polymeric membrane.
 The drug permeability controlled by biochemical
agent in tissue where system is located.
 E.g. glucose-triggered insulin delivery system.
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27.  Self regulating DDS
 Depends on reversible and competitive mechanism to
activate and to regulate the release of drug.
 Drug reservoir is drug complex , encapsulated within
semi permeable polymeric membrane.
 Release of drug from delivery system activated by
membrane permeation of biochemical agent from
the tissue in which the system is located.
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28.  References:-
 Novel drug delivery system.
- By, Chein.
 Controlled release delivery system
- By, J Roseman, Mansdrof.
 Controlled drug delivery , vol.- 1 , Basic concept.
- By, Stephen D Bruck
 Controlled drug bioavaibility, vol.- 3
-By, Victor F. Smolen
Lu Ann Ball.
 Remington science & Practice of Pharmacy, vol.1 , 20th edition
 Indian journal of pharmaceutical science. 2001, 63(1). 24-29.
 Targeted and Controlled drug delivery,
- By, Vyas and Khar
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