TRANSDERMAL DRUG DELIVERY SYSTEM : TRANSDERMAL DRUG DELIVERY SYSTEM V.NAVEEN CHAND
ROLL NO: 16 TRANSDERMAL PATCHES : TRANSDERMAL PATCHES Slide 3: INTRODUCTION
Transdermal drug delivery systems (TDDS), also known as ‘‘patches,’’ are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin .
An ideal dosage form would be maintaining the drug concentration in the blood at a constant level nearly coinciding with the Minimum Effective Concentration (MEC) of drug throughout the treatment period. This leads to the concept of the controlled drug delivery.
The primary objective of controlled drug delivery is to ensure safety and efficacy of the drugs as well as patients compliance.
To optimize this drug delivery system, greater understanding of the different mechanisms of biological interactions, and polymer are required.
TDDS a realistic practical application as the next generation of drug delivery ADVANTAGES : ADVANTAGES Advantages of transdermal delivery system
patch provides a controlled release of the medication into the patient
The system avoids the chemically hostile GI environment
No GI distress or other physiological contraindications of the oral route
Can provide adequate absorption of certain drugs
Increased patient compliance
Avoids first-pass effect
Allows effective use of drugs with short biological half-life
Allow administration of drugs with narrow therapeutic windows
Provides controlled plasma levels of very potent drugs
Drug input can be promptly interrupted when toxicity occurs DISADVANTAGES : DISADVANTAGES Disadvantages of TDS
Drug that require high blood levels cannot be administered
Adhesive may not adhere well to all types of skin
Drug or drug formulation may cause skin irritation or sensitization
Uncomfortable to wear
May not be economical
Consideration of TDS development
Bioactivity of drug
System design Theoretical Advantages of the Transdermal Route : Theoretical Advantages of the Transdermal Route Variables associated with GI absorption
Changes in pH
Gastric emptying, intestinal motility and transit time
Activity of human and bacterial enzymes
Influence of food
Control administration and limit pharmacological action
Minimize pulse entry of a drug into the bloodstream
Not deliberately provide a control on/off action
Skin membranes : slow-response system with prolonged lag time Structure of human skin : Structure of human skin Human skin
The stratified avascular cellular epidermis
An underlying dermis of connective tissue
Stratum corneum or horny layer
Rate-limiting or slowest step in the penetration process
Transepidermal pathway across the horny layer either intra- or intercellularly
Via hair follicles and sweat glands (the appendageal route) Fig. Basic diagram of skin structure : Fig. Basic diagram of skin structure Components : Components The main components to a transdermal patch are:
Liner - Protects the patch during storage. The liner is removed prior to use.
Drug - Drug solution in direct contact with release liner
Adhesive - Serves to adhere the components of the patch together along with adhering the patch to the skin
Membrane - Controls the release of the drug from the reservoir and multi-layer patches
Backing - Protects the patch from the outer environment
Polymer matrix / Drug reservoir
Pressure sensitive adhesive (PSA)
Other excipients like plasticizers and solvents Drug : Drug Drugs with appropriate pharmacology and physical chemistry.
Drugs which undergo extensive first pass metabolism,
drugs with narrow therapeutic window,
drugs with short half life which causes non- compliance due to frequent dosing.
It is generally accepted that the best drug candidates for passive adhesive transdermal patches must be non ionic,
of low molecular weight (less than 500 Daltons),
have adequate solubility in oil and water (log P in the range of 1-3),
a low melting point (less than 200°C) and are
potent (dose in mg per day)
drugs like rivastigmine for alzheimer’s and parkinson dementia,
rotigotine for parkinson, methylphenidate for attention deficit hyperactive disorder
selegiline for depression are recently approved as TDDS. Permeation enhancers : Permeation enhancers These are the chemical compounds that increase permeability of stratum corneum so as to attain higher therapeutic levels of the drug candidate
Penetration enhancers interact with structural components of stratum corneum i.e., proteins or lipids.
They alter the protein and lipid packaging of stratum corneum, thus chemically modifying the barrier functions leading to increased permeability.
Over the last 20 years, a tremendous amount of work has been directed towards the search for specific chemicals, combination of chemicals, which can act as penetration enhancers. Pressure sensitive adhesives : Pressure sensitive adhesives A PSA is a material that helps in maintaining an intimate contact between transdermal system and the skin surface.
It should adhere with not more than applied finger pressure, be aggressively and permanently tachy, exert a strong holding force.
it should be removable from the smooth surface without leaving a residue.
Polyacrylates, polyisobutylene and silicon based adhesives are widely used in TDDS.
The selection of an adhesive is based on numerous factors, including the patch design and drug formulation.
For matrix systems with a peripheral adhesive, an incidental contact between the adhesive and the drug and penetration enhancer should not cause instability of the drug, penetration enhancer or the adhesive.
In case of reservoir systems that include a face adhesive, the diffusing drug must not affect the adhesive.
In case of drug-in-adhesive matrix systems, the selection will be based on the rate at which the drug and the penetration enhancer will diffuse through the adhesive.
Ideally, PSA should be physicochemically and biologically compatible and should not alter drug release Backing laminate : Backing laminate While designing a backing layer, the consideration of chemical resistance of the material is most important.
Excipient compatibility should also be considered because the prolonged contact between the backing layer and the excipients may cause the additives to leach out of the backing layer or may lead to diffusion of excipients, drug or penetration enhancer through the layer.
However, an overemphasis on the chemical resistance may lead to stiffness and high occlusivity to moisture vapor and air, causing patches to lift and possibly irritate the skin during long wear.
The most comfortable backing will be the one that exhibits lowest modulus or high flexibility, good oxygen transmission and a high moisture vapor transmission rate.
Examples of some backing materials are vinyl, polyethylene and polyester films. Release liner : Release liner During storage the patch is covered by a protective liner that is removed and discharged immediately before the application of the patch to skin.
It is therefore regarded as a part of the primary packaging material rather than a part of dosage form for delivering the drug. However, as the liner is in intimate contact with the delivery system, it should comply with specific requirements regarding chemical inertness and permeation to the drug, penetration enhancer and water.
Typically, release liner is composed of a base layer which may be non-occlusive (e.g. paper fabric) or occlusive (e.g. polyethylene, polyvinylchloride) and a release coating layer made up of silicon or teflon.
Other materials used for TDDS release liner include polyester foil and metallized laminates. Other excepients : Other excepients Various solvents such as chloroform, methanol, acetone, isopropanol and dichloromethane are used to prepare drug reservoir.
In addition plasticizers such as dibutylpthalate, triethylcitrate, polyethylene glycol and propylene glycol are added to provide plasticity to the transdermal patch A) Membrane-moderated systems: : A) Membrane-moderated systems: In this system, the drug reservoir is totally encapsulated in a shallow compartment molded from a drug-impermeable metallic plastic laminate and a rate-controlling polymeric membrane.
The drug molecules are permitted to release only through the rate-controlling polymeric membrane.
In the drug reservoir compartment, the drug solids are either dispersed in a solid polymer matrix or suspended in an unreachable, viscous liquid medium, e.g., silicone fluid to form a paste-like suspension.
The rate-limiting membrane- ethylene-vinyl acetate copolymer B. Adhesive Diffusion-Controlled Systems : B. Adhesive Diffusion-Controlled Systems This type of drug delivery system is a simplified version of the membrane moderated drug delivery system outlined above.
Instead of completely encapsulating the drug reservoir in a compartment fabricated from a drug-impermeable metallic plastic backing,
In this system the drug reservoir is formulated by directly dispersing the drug in an adhesive polymer and then spreading the medicated adhesive, by solvent casting, onto a flat sheet of drug-impermeable metallic plastic bucking to form a thin drug reservoir layer. C. Matrix Dispersion – Type Systems: : C. Matrix Dispersion – Type Systems: In this approach, the drug reservoir is formed by homogeneously dispersing the drug solids in a hydrophilic or lipophilic polymer matrix and the medicated polymer is then molded into medicated disc with a defined surface area and controlled thickness.
This drug reservoir-containing polymer disc is then glued onto an occlusive base plate in a compartment fabricated from a drug-impermeable plastic backing. Slide 20: D. Micro reservoir System: This type of drug delivery system can be considered as a combination of the reservoir and matrix dispersion-type drug delivery systems.
In this approach, the drug reservoir is formed by first suspending the drug solids in an aqueous solution of water-soluble polymer and then dispersing homogeneously the drug suspension in a lipophilic polymer by high-shear mechanical force, to form thousands of unleachable, microscopic spheres of drug reservoirs.
This thermodynamically unstable dispersion is quickly stabilized by immediately cross linking the polymer chains in situ, which produces a medicated polymer disc with a constant surface area and a fixed thickness.
A transdermal therapeutic system is produced, in which the medicated disc is positioned at the center and surrounded by an adhesive rim.
This technology has been successfully utilized in the development and marketing of nitroglycerin-releasing transdermal therapeutic system (Nitrodisc system / Searle) for once-a-day treatment of angina pectoris. Fig. 3. Types of transdermal delivery devices. : Fig. 3. Types of transdermal delivery devices. Drug Release : Drug Release Other Transdermal Systems : Other Transdermal Systems Lectec Co.
A solid-state, hydrophilic reservoir system
Transdermal laminar system
Absorbed from bracelets by electrical impulses
Molecular Biotech Co.
Proplastic membrane (molecular sponge) Transdermal Controlled-Release Products and Devices : Transdermal Controlled-Release Products and Devices Transdermal Products under Development : Transdermal Products under Development Slide 31: VIVELLE-DOT
This contains estradiol in a multipolymeric adhesive that helps in the development and maintenance of the female reproductive system and secondary sexual characteristics. Regulatory aspects : Regulatory aspects A transdermal patch is classified by the U.S. Food and Drug Administration as a combination product, consisting of a medical device combined with a drug or biological product that the device is designed to deliver.
Prior to sale in the United States, any transdermal patch product must apply for and receive approval from the Food and Drug Administration, demonstrating safety and efficacy for its intended use. Slide 33: Thank You ….