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7 Design & Development of Implantable Products Presented by: BHUPENDRA Ku YADAV M.Pharm II sem RCPSR, Bhilai, (C.G.) 1
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Design & development of implantable products: By Bhupendra Yadav

Apr 30, 2015

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Implants are cylindrical, monolithic devices of millimeter or centimeter dimensions, implanted into the subcutaneous or intramuscular tissue by an minor surgical incision or injected through a large bore needle; and release the incorporated drug in a controlled manner, allowing the adjustment of release rates over extended periods of time, ranging from several days up to one year.
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Page 1: Design & development of implantable products: By Bhupendra Yadav

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7Design & Development of Implantable Products

Presented by:

BHUPENDRA Ku YADAV

M.Pharm II sem

RCPSR, Bhilai, (C.G.)

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Introduction Implants are cylindrical, monolithic devices of millimeter or

centimeter dimensions, implanted into the subcutaneous or intramuscular tissue by an minor surgical incision or injected through a large bore needle; and release the incorporated drug in a controlled manner, allowing the adjustment of release rates over extended periods of time, ranging from several days up to one year.

Implantable drug delivery systems are placed completely under the skin. 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.

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Anatomy & Physiology of Skin

Features:-•Subcutaneous tissue is essentially a sheet of areolar tissue lying directly underneath the skin.•It is rich in fat, but poor in nerve network & hemoperfusion. Therefore, the subcutaneous tissue is an ideal location for implantation, slow drug absorption & low reactivity to the insertion of foreign materials.

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Ideal Properties of ImplantsBiostable BiocompatibleNon-toxic & non-carcinogenicMinimum surface area & smooth textureEasily removableMedicament Release Rate

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Design & FabricationApproaches For The Development of Implantable Products:

(a) Controlled drug delivery by diffusion process: Polymer membrane permeation- controlled drug delivery:-

a) Nonporous membranes

b) Micro porous membranes

c) Semi permeable membranes Matrix diffusion-controlled drug delivery:-

a) Lipophilic Polymers

b) Hydrophilic(swellable) polymers

c) Porous polymers Micro reservior partition- controlled drug delivery system:-

a) Hydrophilic reservoir/Lipophilic matrix

b) Lipophilic reservoir/Hydrophilic matrix

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(b) Controlled drug delivery by activation process: Osmotic pressure Vapor pressure Hydration Hydrolysis Magnetism

(c) Controlled drug delivery by feed back regulated mechanism:

Bioerosion

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Controlled drug delivery by diffusion process

A) Membrane permeation- controlled drug delivery:-

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.

• Encapsulation of drug formulation in to the reservoir compartment can be done by:

1. Spray coating

2. microencapsulation

drug reservoir

polymeric membraneDrug contained in a formulation

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Different shapes of the systems like sphere , cylinder or sheet can be fabricated

Example:- A NORPLANT SUBDERMAL IMPLANT ,

PROGESTASERT IUD, and

OCUSERT SYSTEM.

b) Matrix diffusion-controlled drug delivery: 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

a) Blending finely divided drug particles with a liquid polymer or a viscous base followed by cross linking of the polymer chain

b) Mixing the drug with a polymer at an elevated temperature

c) Dissolving drug and polymer in a common solvent followed 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

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Example:- Contraceptive Vaginal Ring

Syncro-Mate B Implants

Compudose Implant

c) Micro reservoir Partition- Controlled drug delivery:-

Drug Reservoir- fabricated by aqueous suspension of a drug using high energy dispersion technique into a biocompatible polymer such as silicon elastomer to form a homogenous dispersion of microscopic drug reservoir.

Depending on the physiochemical properties of the drug and the desired rate of drug release, the device can be further coated with polymer to modify mechanism & rate of release.

Example:- Syncro-Mate C Implants

Dual-Release Vaginal Contraceptive Ring

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Polymer matrix

Microscopic Drug reservoir

{liquid compartment}

Coating membrane

Polymer -solution interface

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Controlled drug delivery by activation process

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.

Osmosis is the movement of

a solvent through a semi-permeable

membrane from a region of low- solute

concentration to a region of high-

solute concentration.

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Drug reservoir which can be either a solid or a suspension is contained in a semi permeable housing .

The release is activated through a specially formed orifice and rate of release is modulated by controlling the osmotic gradient.

The release rate is dependent of:

water permeability of membrane,

solubility of osmogen,

effective surface area of semipermeable housing

Representatative example of this type of implantable controlled release drug delivery system is: ALZET Osmotic Pump

DUROS Osmotic Pump

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Vapor pressure-activated implantable drug delivery system:

The drug reservoir which is 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 .

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Magnetism – Activated Drug Delivery:

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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

U

U

U

U U

U

UU

U U UU

U

U

UHydrocortisone

Urea Ammonia

Urease

Alkaline pH

Polymer

Erosion

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Targeted Drug Delivery With Catheterized Osmotic Pumps:

Catheters of different designs can be attached to the exit port of an osmotic pump for targeted drug delivery

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Electrical Regulated Release:Device features:Target: 1+ year implant life. 100 to 400 doses.Reservoir volume ≥100 nL.Accommodates solutions, solids. Individual reservoirs activated

electronically

– Each reservoir can contain a different drug or formulation

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E.g. Silicon Microchip contained an array of reservoirs attached in silicon. The reservoirs were

capped with gold membranes that could be electrochemically dissolved in saline with an applied voltage (through a wireless signal from outside the body). At approximately 1 V, gold chloride is formed, causing the membrane to dissolve.

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Micrographs of gold membranes (a) before and (b) after electrochemical dissolution

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Advantages:◦ Controlled drug delivery for over a long time

(months/years)◦ Improve patient compliance◦ Targeted drug delivery◦ Bypass first pass metabolism◦ Decrease side effects◦ Improved stability of drug◦ Improve availability of drugs

Disadvantages:- mini-surgery is needed- uneasy to simply discontinue the therapy- local reactions

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Any Queries

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Thanks