Approaches of SR/CR delivery system

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

Contents:
 Introduction
 Terminology
 Classification
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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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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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 Plasma drug concentration profile:-
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Classification:
 Rate programmed DDS
 Activation modulated DDS
 Feedback regulated DDS
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Four classes of controlled drug delivery system:-
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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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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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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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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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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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 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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 Alzet osmotic pump:-
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 B) Hydrodynamic pressure activated- DDS
 Depends upon hydrodynamic pressure
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 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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 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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 Mechanically activated drug delivery system
(Mechanical pump)
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 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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 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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 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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 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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 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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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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 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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 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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 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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 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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Approaches of SR/CR delivery system

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