Implantable Drug Delivery System

Approaches to the development of Implantable drug delivery system(Parenteral drug delivery system)
Prepared by:
Paresh K Bharodiya
09PCT07
Guided by:
Dr. Ajay B. Solanki
Department of pharmaceutics
A.R College & G.H Patel Institute of Pharmacy
12/05/2010

List of contents
Effect of physicochemical properties on parenteral absorption
Introduction
Approaches to design implantable drug delivery systems
(a) Controlled drug delivery by diffusion process
Polymer membrane permeation- controlled drug delivery
Matrix diffusion-controlled drug delivery
Microreservior partition-controlled drug delivery system
Membrane matrix hybrid-type drug delivery system
(b) Controlled drug delivery by activation process
Osmotic pressure
Vapor pressure
Magnetically
Hydration
Hydrolysis
(c) Controlled drug delivery by feed back regulated mechanism
Bioerosion
Bioresponce
REFRENCES

Effect of Physicochemical Properties on Parenteral Absorption
Drug particle in suspension
Drug solutes in solution
Dissolution
Partitioning
Absorption
Systematic circulation
Drug solution in tissue fluid
Target tissue
Elimination

Rate of dissolution of solid in formulation vehicle
Particle size and crystal habit
pH of the formulation
pKa of drug
Lipophillicity of the drug
Tissue fluid/vehicle partition coefficient
Solubility of drug at biological fluid at injection site
Presence of other ingredients in the formulation and their interaction with the drug molecule

Implantable drug delivery systeman introduction
Implantable drug delivery systems are placed completely under the skin — usually in a convenient but inconspicuous location. The patient is aware of only a small bump under the skin.
designed to transmit drugs and fluids into the bloodstream without the repeated insertion of needles.
well suited to the drug delivery requirements of insulin, steroids, chemotherapeutics, antibiotics, analgesics, total parenteral nutrition, and heparin
There is little chance of infection or interference with daily activities Because the device is completely subcutaneous, with no opening in the skin

Approaches to the development of Implantable drug delivery system
In 1861 Lafarge pioneered the concept of IDDS for long term continuous administration of crystalline hormone in the form of solid steroid pellet
But the release profile was not constant and can not be readily controlled in terms of precision of the release rate and duration of action
While it is possible to surgically implant and remove drug-concentrative devices or polymeric matrices, the requirement for such intervention could have a significant negative impact on the acceptability
Two approaches to this problem seem possible
Use of implanted electrically driven pumps
Use of erodible implants

Number of approaches have been developed to achive controlled administration of drugs via implantation
(1) Controlled drug delivery by diffusion process
Diffusion of the drug out of the device or solvent into the polymer ultimately contributes to the drug-release process
Release of the drug from the device is preprogrammed at a specific rate profile
This is accomplished by a system design which controls molecular diffusion of drug in or and/or across barrier medium surrounding the system
This systems can be further sub classified in to number of classes

(A)Polymer membrane permeation- controlled drug delivery using
Non porous membrane
Micro porous membrane
Semi permeable membrane
Here the drug formulation is totally or partially encapsulated within a drug reservoir compartment and the drug release surface is covered by a rate limiting polymeric membrane having a specific permeability for drug
drug reservoir
polymeric membrane
Drug contained in a formulation

The dug reservoir can exist in to a solid , suspension or in a solution form and polymeric membrane fabricated in the form of non porous{homogenous or heterogeneous}, micro porous or semipermiable membrane.
Encapsulation of drug formulation in to the reservoir compartment can be done by
Injection molding
Spray coating
microencapsulation
Different shapes of the systems like sphere , cylinder or sheet can be fabricated
An example of this type of implantable drug delivery system is A NORPLANT SUBDERMAL IMPLANT and OCUSERT SYSTEM

(b) Polymer Matrix diffusion-controlled drug delivery
In this type of preplanned drug delivery system the drug reservoir is prepared by homogenous dispersion of drug particles in a rate controlling polymer matrix fabricated from either a lipophillic or a hydrophilic polymer
The drug dispersion in a polymer matrix is done by
Blending finely divided drug particles with a liquid polymer or a viscous base followed by cross linking of the polymer chain
Mixing the drug with a polymer at an elevated temperature
Dissolving drug and polymer in a common solvent followe by solvent evaporation at elevated temperature or under vacuum
The resultant drug polymer dispersion is then molded or extruded to form a drug delivery devices of various shapes
Example is a nitro-dur TDDS

Drug reservoir{dispersion}
Drug release
Gel layer
Drug depleted zone
Drug release
Hydrophilic polymer
Swollable matrix
Lipophillic polymer
Non swollable matrix

(C) Microreservior partition-controlled drug delivery system
In this type drug reservoir is fabricated by micro dispersion of aqueous suspension of a drug using a high energy dispersion technique in to a biocompatible polymer such as silicone elastomer to form a homogenous dispersion of many discrete , unreachable microscopic drug reservoir
Depending on the physicochemical properties of the drug and the desired rate of drug release , the device can be further coated with polymer to modify mechanism and rate of release
example is the transdermal nitro disc system

Polymer matrix
Microscopic Drug reservoir
{liquid compartment}
Coating membrane
Polymer -solution interface

(d) Membrane matrix hybrid-type drug delivery system
This device is a hybrid of Polymer Matrix diffusion-controlled drug delivery and Polymer membrane permeation- controlled drug delivery system aim is to take advantage of controlled release kinetic offered by Polymer membrane permeation- controlled drug delivery system and to avoid risk of dose dumping from reservoir compartment of this type of drug delivery system
Drug reservoir is formed by dispersion of drug in to a polymer matrix which is further coated by a semi permeable polymeric membrane
Example is a norplant II sub dermal system

(II) Controlled drug delivery by activation process
In this type release of the drug is activated by some physical , chemical, or biological process and/or by the energy supplied externally and the rate of release is than regulated by the processes applied or input of energy
Based on the processed applied these activation modulated drug delivery system can be classified in to
Osmotic pressure activated
Vapor pressure activated
Magnetically activated
Hydrolytic-activated
Hydration activated

Osmotic pressure activated drug delivery system
In this type of controlled drug delivery system the release of the drug takes place due to osmotic pressure
Drug reservoir which can be either a solid or a suspension is contained in a semipermiable housing
The release is activated through a specially formed orifice and rate of release is modulated by controlling the osmotic gradient
Thus release rate is dependent on water permeability of membrane, solubility of osmogen, effective surface area of semipermiable housing as well as osmotic gradient
Representatative example of this type of implantable controlled release drug delivery system is alzet osmotic pump

Alzet osmotic pump

Vapor pressure activated implantable drug delivery system
The drug reservoir which ids a solution formulation is contained in to an infusate chamber
By freely movable bellow the chamber is a pumping system physically separated from the vapors pressure chamber which contains vaporizable fluids such as a fluorocarbon
The fluorocarbon vaporizes at body temperature creating a vapor pressure that pushes bellow to move upward and forces the drug solution to get delivered

Magnetically activated implantable drug delivery system
A magnetic wave triggered mechanism is incorporated in to drug delivery device and drug can be triggered to be released at varying rate depending on the magnitude and duration of the electromagnetic energy applied
Magnetic ring
Coated polymer
Magnet inside polymer matrix

Hydration activated drug delivery system
This system depends on the hydration induced swelling process by tissue fluid at implantable site to activate drug release
In this system drug reservoir is dispersed in to swollable polymer matrix fabricated from hydrophilic polymer that become swollen upon hydration
Drug is released from microscopic water filled pore channels in to the polymer matrix and
Release rate of drug is controlled by swelling of the polymer matrix

Hydrolysis activated drug delivery system
Release of drug is activated by hydrolysis of a bioerodable polymer by the cell fluid at the implantation site
Biodegradable polymer like
Co(lactic-glycolic)polymer
Poly(orthoester)
Poly(anhydride) are used in fabrication of this type of implantable drug delivery system
This system is made by dispersing loading dose of a drug with a biodegradable polymer , which is then molded in to pellet or a bead shaped implant
Example is a LHRH{goserelin} releasing biodegradable sub dermal implant

(c) Controlled drug delivery by feed back regulated mechanism
using this group of controlled drug delivery system the release of a drug is activated by some biochemical molecule in the body and its concentration at the implantable site via feedback mechanism
And the rate of controlled release of drug is regulated by the concentration of biochemical substance detected by a sensor in the feedback mechanism

Bioerosion regulated drug delivery system
This system consist of a drug dispersed in to a biodegradable polymer matrix like poly vinyl methyl ether and is coated with immobilized urease in a neutral pH.in the presence of urea urease at the surface of drug delivery system metabolize urea to form ammonia causing increase in pH at which polymer degrades leading to drug release
Hydrocortisone release
Urease
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
Erosion
Ammonia
Urea
Hydrocortisone
Alkaline pH
Polymer

Bioresponce activated drug delivery system
Drug reservoir is contained in a device enclosed by a bioresponsive polymer membrane whose permeability is controlled by conc. of a biochemical agent contained where the system is located
Example is a glucose triggered insulin delivery system in which insulin reservoir is capsulated within hydrogel membrane having amineNR2 groups
In alkaline pH NR2 is neutral and membrane is unsellable and impermeable to insulin
As glucose, triggering agent penetrates in to membrane it is oxidized to glucuronic acid by enzyme glucose oxidise contained in a membrane
NR2 groups are protonated and hydro gel membrane becomes swollable and permeable for insulin.
Amt of release is dependant on the concentration of glucose entering in to membrane

REFRENCES
NOVEL DRUG DELIVERY SYSTEM, Yie. W Chien, second edition, marceldekker inc, page 381
DRUG DELIVERY SYSTEMS, Vasant V. RanadeMannfred A. Hollinger Second Edition,

Implantable Drug Delivery System

by paresh bharodiya on May 13, 2010

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