controlled drug delivery system classification

Controlled Drug Delivery SystemControlled Drug Delivery SystemClassificationClassification

Activation-modulated Drug Delivery SystemActivation-modulated Drug Delivery System

22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. 2

In this group of controlled release drug delivery system, the release of drug molecules from the delivery system is activated by some physical, chemical, or biochemical process and/or by energy supplied externally.

The rate of drug release is then controlled by regulating the process applied or energy input.

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Classification : By Physical MeansClassification : By Physical Means

22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P.

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Activation-Activation-Modulated Modulated

DDSDDS


DDSDDS

Osmotic pressure Activated

Osmotic Pressure ActivatedOsmotic Pressure Activated DDSDDS


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Drug reservoir ( API + osmotic agent)

Delivery Orifice

Semi-permeable Membrane.(cellulose esters)


For the drug delivery system containing a solution formulation, the intrinsic rate of drug release is defined by,

Q Pw Am t hm

For the drug delivery system containing a solid formulation, the intrinsic rate of drug release is defined by,

Q Pw Am t hm

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( πs – πe )==

( πs – πe ) Sd==


Where,Where,Q/t - rate of drug release

Pw - permiability of semipermiable housing

Am -effective S.A. of semipermiable housing

hm - thickness of semipermiable housing

(π s - π e) – Differential osmotic pressure b/w

DDS with osmotic pressure ps &

environmental osmotic pressure pe

Sd – Aqueous solubility of drug contained in the

solid formulation.

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Release is controlled at rate determined by,Release is controlled at rate determined by,

Water permeability Surface area of semi-permeable housing Osmotic pressure gradient

Merits :Merits :

A high degree of in vivo- in vitro correlation (IVIVC) is obtained in osmotic systems.

For oral osmotic systems, drug release is independent of gastric pH and hydrodynamic conditions.

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8 8Alzet Osmotic Pump



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DDSDDS


DDSDDS

Osmotic pressure Activated Hydrodynami

cPress. Activated

Hydrodynamic Pressure - Activated DDSHydrodynamic Pressure - Activated DDS


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Rate of drug release is defined by,

Where,Where,

Pf = fluid permeability

Am = effective Surface area

hm = thickness of wall with anular opening

(s - e)= differential hydrodynamic pressure

between DDS and environment.

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Q Pf Am t hm

== ( s - e)


Release is controlled at rate Release is controlled at rate determined by,determined by,

Fluid permeability Pressure gradient Surface area of wall with annular opening

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DDSDDS


DDSDDS


cPress. Activated

Vapor Pressure Activated

Vapor Pressure – Activated DDSVapor Pressure – Activated DDS


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The rate of drug release is defined by, Q = d4 (Ps -Pe)

t 40.74 mlWhere-Where- Q/t - rate of drug release d - Inner diameter of cannula l - length of cannula(Ps -Pe) - the difference between the vapor

pressure in the vapor chamber & pressure at the implantation site.

m - viscosity of the drug solution.15


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Rate controlled By :Rate controlled By : Differential vapor pressure Formulation viscosity Size of the delivery cannula

Example, An implantable infusion pump for

constant infusion of heparin in anticoagulant

treatment, morphine for patients suffering from the intense pain of terminal cancer.

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DDSDDS


DDSDDS


cPress. Activated


MechanicallyActivated

Mechanically – ActivatedMechanically – Activated DDSDDS


In this type, drug reservoir is in solution form retained in a container equipped with mechanically activated pumping system.

A measured dose of the drug formulation is reproducible delivered in to a body cavity, for ex. The nose, through the spray head upon manual activation of the drug delivery pumping system.

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Ex. Metered-dose InhalerEx. Metered-dose Inhaler

the volume of solution delivered is controllable, as small as 10-100 μl & is independent of the force & duration of the activation applied as well as the solution volume in the container.

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DDSDDS


DDSDDS


cPress. Activated


MechanicallyActivatedMagnetically

Activated

Magnetically Activated - DDSMagnetically Activated - DDS


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In this type, drug reservoir is a dispersion of peptide or protein powders in polymer matrix from which macromolecular drug can be delivered only at a relatively slow rate.

Device is fabricated by positioning a tiny magnet ring in core of hemispherical drug dispersing polymer matrix.

The external surface is coated with drug impermeable polymer (ethylene vinyl acetate or silicone elastomer) except one cavity at the centre of the flat surface.

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e.g.e.g. This delivery device used to deliver protein drugs such as bovine serum albumin, at a low basal rate, by a simple diffusion process under non triggering condition.

As the magnet is activated to vibrate by an external electromagnetic field, the drug molecules are delivered at a much higher rate.

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DDSDDS


DDSDDS


cPress. Activated



Activated

SonophoresisActivated

Sonophoresis - Activated DDSSonophoresis - Activated DDS


This type of system utilizes ultrasonic energy to activate or trigger the delivery of drug from polymeric drug delivery device.

System can be fabricated from nondegradable polymer (ethylene vinyl acetate) or bioerodiable polymer (poly[bis(p-carboxyphenoxy) alkane anhydride].

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22/01/2011

B R Nahata College of Pharmacy ,Mandsaur M.P.

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DDSDDS


DDSDDS


cPress. Activated



Activated


Ionto-phoresisActivated

Iontophoresis - Activated DDSIontophoresis - Activated DDS


Iontophorsis can be defined as the process in which the flux or rate of absorption of ionic solutes into or through skin is enhanced by applying a voltage drop/electrical field across the skin.

In addition, delivery rate can be controlled by the intensity of applied electric current or Electro-chemical potential gradient.

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Iontophoresis – facilitated skin permeation rate of charged molecule (i) consist of 3 components & is expressed by,

Jiisp = Jp + Je +Jc

Jp – passive skin permeation flux. Je – electrical current driven permeation

flux Jc = convective flow driven skin

permeation flux

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Merits :Merits :


Non-invasive technique as a substitute for chemical enhancers.

Frequency of dosage is reduced. Provide predictable and extended

duration of action.Demerits :Demerits : Excessive current density leads to pain. The safe current density varies with

electrode size. Mol. Wt. of 8000-12000 results in a

uncertain rate of delivery.

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DDSDDS


DDSDDS


cPress. Activated



Activated


Ionto-phoresisActivated

Hydration Activated

Hydration - Activated DDSHydration - Activated DDS


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Valrelease Tablets


Not only hydrophilic polymer but also the lipophilic polymers, such as silicone elastomer, can be modified to have swelling properties.

This is achieved by impregnating water-miscible liquid such as glycerol and/or water soluble salt such as, sodium chloride, in lipophilic polymer matrix.

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Classification By : Chemical MeansClassification By : Chemical Means


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DDSDDS


DDSDDS

pH-Activated DDS

pH-Activated DDS


This type of chemically activated system permits targeting the delivery of drug only in the region with selected pH range.

It fabricated by coating the drug-containing core with a pH – sensitive polymer combination.

For instances, a gastric fluid labile drug is protected by encapsulating it inside a polymer membrane that resist the degradative action of gastric pH, such as combination of ethyl-cellulose and hydroxymethylcellulose phthalate.

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DDSDDS


DDSDDS

pH-Activated DDS

Ion-Activated DDS

Ion-Activated DDSIon-Activated DDS


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An ionic or a charged drug can be delivered by this method & this system are prepared by first complexing an ionic drug with an ion-exchange resin containing a suitable counter ion.

Ex. By forming a complex between a cationic drug with a resin having a So3

-

group or between an anionic drug with a resin having a N(CH3)3 group.

The granules of drug-resin complex are first treated with an impregnating agent & then coated with a water-insoluble but water-permeable polymeric membrane.

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This membrane serves as a rate-controlling barrier to modulate the influx of ions as well as the release of drug from the system.

Limitations :Limitations :

The rate of release of the drug is directly proportional to the concentration of ions at the site of action.

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DDSDDS


DDSDDS

pH-Activated DDS

Ion-Activated

DDS

Hydrolysis-Activated

DDS

Hydrolysis-Activated DDSHydrolysis-Activated DDS


This type of system depends upon hydrolysis process to activate the release of drug.

Drug reservoir is either encapsulated in microcapsules or homogeneously dispersed in microspheres or nano particles for injection.

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It can also be fabricated as an implantable device.

All these systems prepared from bioerodible or biodegradable polymers (polyanhydride, o-(polyanhydride, o-ester).ester).

It is activated by hydrolysis-induced degradation of polymer chain & is controlled by rate of polymer degradation.

Ex. LHRH – releasing biodegradable subdermal implant, which is designed to deliver goserline, a synthetic LHRH analog for once a month treatment of prostate carcinoma.

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Classification By : Biochemical MeansClassification By : Biochemical Means


Enzyme - Activated Drug Delivery Enzyme - Activated Drug Delivery SystemSystem

This type of biochemical system depends on the enzymatic process to activate the release of drug.

Drug reservoir is either physically entrapped in microspheres or chemically bound to polymer chains from biopolymers (albumins or polypeptides).

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The release of drug is activated by enzymatic hydrolysis of biopolymers (albumins or polypeptides) by specific enzyme in target tissue.

Ex.Ex. Albumin microspheres release 5 – fluorouracil in a controlled manner by protease – activated biodegradation.

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Feedback Regulated Drug Delivery SystemFeedback Regulated Drug Delivery System


In this group the release of drug molecules from the delivery system is activated by a triggering agent.

Rate of drug release is controlled by concen. of triggering agent.

They are further classified as

A. Bioerosion -regulated drug delivery system

B. Bioresponsive drug delivery system

C. Self-regulating drug delivery system

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A. Bioerosion - Regulated DDSA. Bioerosion - Regulated DDS


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.Bioresponsive DDS.Bioresponsive DDS


in this type, the drug reservoir is contained in a device enclosed by bio-responsive membrane whose drug permeability is controlled by conce. of biochemical agent.

e.ge.g. glucose-triggered insulin drug delivery system.

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C. Self-Regulating DDSC. Self-Regulating DDS


This type of system depends on a reversible & competitive binding mechanism to activate and to regulate the release of drug.

Drug reservoir is drug complex encapsulated within a semi permeable polymeric membrane.

The release of drug from the delivery system is activated by the membrane permeation of biochemical agent from the tissue in which the system is located

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Effect Of System Parameters On CDDSEffect Of System Parameters On CDDS


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Polymer & Solution Solubility

Polymer & Solution Diffusivity

Thickness of polymer diffusion path & hydrodynamic layer

Partition Co-efficient

Surface Area

Loading Dose

Polymer SolubilityPolymer Solubility


For drug to be release, the drug molecules on the outmost surface must dissociate from its crystal lattice structure, partition or dissolve in surrounding medium.

As the solubility of drug particles in rate controlling membrane and polymer matrix plays rate-controlling role in release from a polymeric device. To release at an appropriate rate the drug should have adequate polymer solubility.

Rate of drug release is directly proportional to magnitude of polymer solubility.

Solution SolubilitySolution Solubility


Aqueous solubility varies from one drug to another.

Difference in aqueous solubility is depend on the difference in their chemical structure, types & physicochemical nature of functional groups & the variations in their stereo chemical configurations.

Drug release increases with increase in Solution solubility of drug.

Partition CoefficientPartition Coefficient


Partition co-efficient K of a drug for it’s interfacial partitioning from the surface of a drug delivery device towards an elution medium as given :

K = Cs/Cp

Where,

Cs = conc. Of drug at the solution/polymer

interface

Cp = solubility of drug in the polymer phase.


Any variation in either Cs or Cp result in

increase or decrease in magnitude of ‘K’ value.

Rate of drug release increase with increase in partition coefficient

Polymer DiffusivityPolymer Diffusivity


The diffusion of small molecules in a

polymer structure is a energy activated

process in which the diffusant molecules

move to a successive series of equilibrium

positions when a sufficient amount of

energy of activation for diffusion Ed, has

been acquired by the diffusant & it’s

surrounding polymer matrix.


Magnitude of polymer diffusivity is dependant upon type of functional group and type of stereo chemical position in diffusant molecule.

The bulkier the functional group attached to polymer chain lower the polymer diffusivity.

Polymer diffusivity also depends on , 1) Effect of cross linking (inverse relationship) 2) Effect of crystallinity (inverse relationship) 3) Effect of fillers

Solution DiffusivitySolution Diffusivity


The diffusion of solute molecules in solution medium is a result of the random motion of molecules.

Under concentration gradient molecule diffuse spontaneously from higher concentration to lower concentration.

Diffusivity of solute molecule in aqueous solution usually decreases as its concentration increases


Thickness of hydrodynamic diffusion layer

Surface Area

Loading Dose.

ReferenceReference


• Novel Drug Delivery System- Y.W.Chien. published by Marcel Dekkar, inc., New

York Pg no. 17-36 & 57-111

• Controlled And Novel Drug Delivery – N.K.Jain CBS Publishers & Distributors, New Delhi.

• www.pharmainfo.net


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controlled drug delivery system classification

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