cdds classification

Controlled Drug Delivery SystemClassification

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

Activation-modulated Drug Delivery System22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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.*


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure Activated


Osmotic Pressure Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *

*Drug reservoir ( API + osmotic agent)Delivery OrificeSemi-permeable Membrane.(cellulose esters)


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

*( s e )

=( s e ) Sd=


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Where,Q/t - rate of drug releasePw - permiability of semipermiable housing Am -effective S.A. of semipermiable housinghm - thickness of semipermiable housing ( s - 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. *


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. * Release is controlled at rate determined by,

Water permeability Surface area of semi-permeable housingOsmotic pressure gradient

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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22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Alzet Osmotic Pump


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated


Hydrodynamic Pressure - Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Rate of drug release is defined by,

Where, Pf = fluid permeability Am = effective Surface area hm = thickness of wall with anular opening (qs - qe)= differential hydrodynamic pressure between DDS and environment.*Q Pf Am t hm =( qs - qe)


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. * Release is controlled at rate determined by,

Fluid permeabilityPressure gradientSurface area of wall with annular opening

*


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure Activated


Vapor Pressure Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *The rate of drug release is defined by, Q = d4 (Ps -Pe) t 40.74 mlWhere- 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.

*


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. * Rate controlled By :Differential vapor pressureFormulation viscositySize 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. *


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure ActivatedMechanicallyActivated


Mechanically Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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.*


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Ex. Metered-dose Inhaler

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

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Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure ActivatedMechanicallyActivatedMagnetically Activated


Magnetically Activated - DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


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

*


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


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure ActivatedMechanicallyActivatedMagnetically ActivatedSonophoresisActivated


Sonophoresis - Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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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22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure ActivatedMechanicallyActivatedMagnetically ActivatedSonophoresisActivatedIonto-phoresisActivated


Iontophoresis - Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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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22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 fluxJc = convective flow driven skin permeation flux

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Merits :22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Non-invasive technique as a substitute for chemical enhancers.Frequency of dosage is reduced.Provide predictable and extended duration of action.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.*


Classification : By Physical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSOsmotic pressure ActivatedHydrodynamicPress. Activated Vapor Pressure ActivatedMechanicallyActivatedMagnetically ActivatedSonophoresisActivatedIonto-phoresisActivatedHydration Activated


Hydration - Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Valrelease Tablets


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSpH-Activated DDS


pH-Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *

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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Classification By : Chemical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSpH-Activated DDS Ion-Activated DDS


Ion-Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


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

*


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

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

*


Classification By : Chemical Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Activation-Modulated DDSpH-Activated DDS Ion-Activated DDSHydrolysis-Activated DDS


Hydrolysis-Activated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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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22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *It can also be fabricated as an implantable device.All these systems prepared from bioerodible or biodegradable polymers (polyanhydride, o-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 Means22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Enzyme - Activated Drug Delivery System

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).

*


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *The release of drug is activated by enzymatic hydrolysis of biopolymers (albumins or polypeptides) by specific enzyme in target tissue.Ex. Albumin microspheres release 5 fluorouracil in a controlled manner by protease activated biodegradation.

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Feedback Regulated Drug Delivery System22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 Bioerosion -regulated drug delivery system Bioresponsive drug delivery system Self-regulating drug delivery system*


A. Bioerosion - Regulated DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **


.Bioresponsive DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. * 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.g. glucose-triggered insulin drug delivery system.

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C. Self-Regulating DDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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*


Effect Of System Parameters On CDDS22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. **Polymer & Solution Solubility

Polymer & Solution Diffusivity

Thickness of polymer diffusion path & hydrodynamic layer

Partition Co-efficient

Surface Area

Loading Dose


Polymer Solubility22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 Solubility22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 Coefficient22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Partition co-efficient K of a drug for its 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 interfaceCp = solubility of drug in the polymer phase.


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 Diffusivity22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *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 & its surrounding polymer matrix.


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

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


22/01/2011B R Nahata College of Pharmacy ,Mandsaur M.P. *Thickness of hydrodynamic diffusion layer

Surface Area

Loading Dose.


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


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


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cdds classification

Documents

release of drug molecules

intrinsic rate of drug

drug releasepw permiability

qt rate

oral osmotic systems

s e sd

effective surface area

solid formulation