“POLYMER MEMBRANE PERMEATION CONTROLLED DRUG DELIVERY SYSTEM”

Sustained release, sustained action, controlled release,

extended action, timed release dosage forms are the terms

used to identify drug delivery systems that are designed to

achieve a prolonged therapeutic effect by continuously

releasing medication over an extended period of time after

the administration of single dose.

The term “Controlled release” has become associated

with those systems from which therapeutic agents may be

automatically delivered at predefined rates over a long

period of time.

But, there are some confusion in terminology between

“Controlled release” & “Sustained release”

Sustained Release :

The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed &/or prolonged & its plasma profile is sustained in duration.

Controlled Release :

This term on the other hand, has a meaning that goes beyond the scope of sustained drug action.

It also implies a predictability & reproducibility in the drug release kinetics, which means that the release of drug ingredient from a controlled delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to another.

An ideal controlled drug delivery system is the one which delivers the drug at a predetermined rate, locally or systematically for a specified period of time.

Biopharmaceutic Characteristics of the DrugMolecular weight, Aqueous solubility, Partition coefficient,

Drug Pka and Ionization, Route of administration, Drug stability etc

Pharmacokinetic Characteristics of the DrugAbsorption rate, Elimination Half-Life, Rate of metabolism etc.

Pharmacodynamic Characteristics of the Drug

Therapeutic Range, Therapeutic index, Plasma concentration response relatioship

These are some of the first materials selected for delivery systems bases on their intended non-biological physical properties:

Polyurethanes for elasticity

Polysiloxanes for insulating ability

Polymethyl methacrylate for physical strength and transparency

Polyvinyl alcohol for hydrophilicity and swelling

Polyvinyl pyrrolidone for suspension capabilities

These polymers became usable in controlled delivery due to their inert physical characteristics and being free of leachable impurities

Poly 2-hydroxy ethyl methacrylate Poly N-vinyl pyrrolidone Polyvinyl alcohol Polyacrylic acid Polyethylene glycol Polymethacrylic acid

Number of approaches have been developed to achievecontrolled administration of drugs via implantation

(1) Controlled drug delivery by diffusion process

Diffusion of the drug out of the device or solvent intothe polymer ultimately contributes to the drug-releaseprocess

Release of the drug from the device is preprogrammedat a specific rate profile

This is accomplished by a system design whichcontrols molecular diffusion of drug in or and/oracross barrier medium surrounding the system

This systems can be further sub classified in to numberof classes

Based on their technical sophistication :

Rate preprogrammed drug delivery system

Activation-modulated drug delivery system

Feedback-regulated drug delivery system

Site targeting drug delivery system

In this group , the release of drug molecule from the system has been preprogrammed at specific rate profile.

They can be classified as

1. Polymer membrane permeation-controlled drug

delivery system

2. Polymer matrix diffusion-controlled drug delivery system

3. Micro-reservior partition-controlled drug delivery

system

In this type, drug is totally or partially encapsulated within

drug reservoir.

Its drug release surface is covered by a rate-controlling

polymeric membrane having a specific permeability.

Drug reservoir may exist in solid, suspension or solution

form drug reservoir

Polymeric membrane

Drug contained in a formulation

Polymer membrane permeation- controlled drug delivery using

1. Non porous membrane2. Micro porous membrane3. Semi permeable membrane

The dug reservoir can exist in to a solid , suspension or in asolution form and polymeric membrane fabricated in the form ofnon porous{homogenous or heterogeneous}, micro porous orsemi-permeable membrane.

Encapsulation of drug formulation in to the reservoircompartment can be done by:

1. Injection molding2. Spray coating3. 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 Systems.

Polymer Membrane Permeation-Controlled Drug Delivery

System

Fig: Diagrammatic representation of membrane permeation controlled system in which drug reservoir is stacked between the layers of drug impermeable plastic laminate and rate controlling membrane and below which the adhesive layers faces the skin surface.

Release of drug molecules is controlled by :

Partition coefficient of the drug molecule.

Diffusivity of the drug molecule.

The thickness of the rate controlling membrane.

The rate of drug release is defined by,

Q = Km/r Ka/m DdDm x CR

t Km/r Dmhd + Ka/m Ddhm

Where,

Km/r & Ka/m = partition coefficient of the drug molecule from reservoir to rate controlling membrane & from membrane to aq. Layer respectively.

Dd & Dm = diffusion coefficient of rate controlling membrane & aqueous diffusion layer respectively.

hm & hd = thickness of rate controlling membrane & aqueous diffusion layer respectively.

CR – drug conc. In reservoir compartment.

Ocusert system

In this device, the solid drug reservoir, which is a thin disc ofpilocarpine alginate, is sandwiched between two transparent sheets ofmicroporous membrane fabricated from ethyvinly acetate copolymer.

It is designed permit the tear fluid to penetrate the microporous membranes, to dissolve and to carry out pilocarpine at a constant rate of 20 to 40 mcg/hr for weekly management of glaucoma.

• Norplant is implanted under the skin in the upper arm of a woman, by creating a small incision.

• inserting the capsules in a fanlike shape.

• Insertion of Norplant usually takes 15 minutes

• the contraceptive works within 24 hours and lasts up to five years.

The drug reservoir is a suspension of progesterone & barium sulphate in silicone medical fluid & is encapsulated in the vertical limb of a T-shaped device walled by a non-porous membrane of ethylene-vinyl acetate co-polymer.

It is designed to deliver natural progesterone continuously in uterine cavity at a daily dosage rate of at least 65 μg/day to achieve contraception for 1 year.

Ex. Progestasert IUD

Drug Reservoir :

dispersed on solid polymer matrix eg. polyisobutylene.

Suspended in unleachable viscous liquid medium eg. Silicone fluid.

Dissolved in solvent.

Rate controlling Membrane: Microporous, Nonporous. Eg. Ethylene-Vinyl acetate copolymer.

Adhesive Layer: Thin layer, adhesive, drug compatible, hypoallergic, eg. Silicone adhesive.

Polymeric Membrane Permeation Controlled Release Drug Delivery System

Advantages :

1. Less fluctuation in drug blood levels.

2. Frequency reduction in dosing.

3. Improved patient convenience & compliance.

4. Increased safety margin of the high potency drugs.

5. Reduction in total health care cost.

Disadvantages :

1. Decreased systemic availability in comparison to immediate release conventional dosage forms.

2. Poor in vivo – in vitro correlation.

3. Possibility of dose dumping.

4. Retrieval of drug is difficult.

5. Higher cost of formulation.