Transdermal drug delivery systems TDDS03

Drug delivery systems

1. TRANSDERMAL DRUG DELIVERY SYSTEM Administration of therapeutic agents through the intact skin for systemic effect. Formulation approaches used in the development of TDDS Introduction these are safe contained self-discrete dosage forms Are applied to the intact skin Deliver the drug at a controlled rate to the system. For example a simple patch that you stick onto your skin like an adhesive bandage which utilizes passive diffusion of drugs across the skin as the delivery mechanism.

2. Advantages It delivers a steady infusion of the drug over an extended period of time. Adverse effects and therapeutic failures can be avoided. It increases the therapeutic value of many drugs by avoiding specific problems associated with the drug. The simplified medication regimen leads to an improved patient compliance and reduce inter patient and intra patient variability. Self-medication is possible with this type of system

3. Disadvantages Drug most have some desirable physic chemical properties to penetrate through the skin Drugs daily dose less than 5mg/day are preferred, if the drug dose is more than 10 -25 mg/day, the TDD will be difficult. Local irritation at the site of administration may be caused by drug, adhesives/other excipients in patch. Clinical need must be clearly established The barrier function of the skin changes from one site to another, from person to person and with age. Poor skin permeability limits the number of drug that can be delivered via this route TDDS cannot deliver ionic drug TDD cannot achieve high drug levels in blood/plasma Drugs of large molecular size cannot be formulated as TDD TDD cannot deliver the drug in pulsatile fashion

4. Characteristics of TDDS The drug input can be terminated at any point of time by removing the patch. Drug most have the desired physicochemical properties for penetration through the stratum corneum. Skin irritation or contact dermatitis due to excipients and enhancers of the drugs used to increase the absorption . it is the other limitation. The barrier function of the skin changes from one site to the other on the same person, from person to person and with age. Heat, cold, sweating (perspiring) and showering prevent the patch from sticking to the surface of the skin for more than one day. A new patch has to be applied daily. The patches fall off during bathing or swimming, patches fall of during walking. Slight movement and sweating will cause patches not to stick.

5. Structure of the Skin Anatomically the skin has many histological layers, but it is divided into divided into: Epidermis Dermis Subcutaneous

6. EPIDERMIS Epidermis is divided into The Stratum corneum and Germinativum The stratum corneum forms the outer most layer of the epidermis and consist of many impacted flattened, dehydrated keratinized cells in the stratified layer. Water content of the stratum corneum is about 20% The moisture required for stratum corneum is around 10% to maintain flexibility. The stratum corneum is responsible for the barrier function of the skin and behaves as a primary barrier to the percutaneous absorption. It is made up of three layers in thicker parts; stratum granulosum , stratum lucidum , stratum spinosum . Removal of these layers results in increased permeability and water loss.

7. DERMIS The dermis is made up of regular network of robust collagen fibers of fairly uniform thickness and regularly placed cross striation. This network or the gel structure is responsible for the elastic properties of the skin. Below the dermis is a fat containing subcutaneous tissue. Upper portion of the dermis formed ridges containing lymphatic and nerve endings.

8. Subcutaneous This is a sheet of fat containing areolar tissue known as the superficial fascia attaching the dermis to the underlying structures.

9. Permeation Through the Skin This occurs by the following routes Transepidermal Absorption Transfollicular (Shunt Pathway Absorption) Clearance by Local Circulation

10. Transepidermal Absorption : Stratum corneum is the main resistance for absorption through this route. Permeation involves partitioning of the drug into the stratum corneum. Permeation through the skin depends upon the O/W distribution tendencies of the drug. Lipophilic drug concentrate in and diffuse with relative ease. Permeation through the dermis is through the interlocking channels of the ground substance.

11. Transfollicular Absorption The skin appendages are considered as shunts for by passing the stratum corneum. The follicular route is important for the permeation because the opening of the follicular pore is relatively large and sebum aids in the diffusion of the penetration. Partitioning into the sebum followed by the diffusion to the depths of the epidermis is the mechanism.

12. Clearance by Circulation The earliest point of entry of drugs into the systemic circulation is within the papillary plexus in the upper epidermis. The process is thus regarded as the end point.

13. Factors Affecting Permeation through Skin Age Blood Flow (dermal clearance of the molecule transversing the tissue) tends to decrease with age and could reduce transdermal flux. Other factors Stratum corneum thickness Presence of hair follicle Injury or trauma to the skin Hydration of the skin Effect of humidity and temperature Chemical exposure Chronic use of certain drugs.

14. Basic Components of TDDS The components of TDDS include Polymer Matrix The drug The permeation enhancers Other excipient.

15. Polymer Matrix It releases drug from the device and should satisfy the following molecular weight, chemical functioning of the polymer should be such that specific drug diffuses properly and gets released through it. It should be stable, non reactive with the drug, easily manufactured and fabricated into the desired product. The polymer and its degradation products must be non toxic or non antagonistic to the host. The mechanical properties of the polymer should not deteriote excessively when the large amount of the active agents are incorporated into it. These polymers used in the transdermal drug delivery system are NATURAL POLYMERS; cellulose derivatives, zein, gelatin, shellax , waxes, proteins, gums and their derivatives, natural rubber starch etc.

16. Synthetic elastomers ; poly butadiene, hydrin rubber, poly siloxane silicon rubber, nitrile, acrylonitrile, butyl rubber, butadiene neoprene etc. Synthetic polymers -polyvinyl chloride, polyethylene, poly propylene, polyacrylate , polyamide, polyurea , etc SKIN SURFACE The skin surface has a population of microorganisms and can contribute to enzymology. The diversity and abundance caries from individual to individual. The microorganisms alter the skin surface lipid composition via hydrolysis of secreted sebum.

17. Clearance by Local Circulation The earliest point of entry of drugs into the systemic circulation is within the papillary plexus in the upper epidermis. The process is thus regarded ad the end point.

18. Drug For successful development of transdermal drug delivery, the following are desirable properties of a drugs for transdermal drug delivery. Physicochemical properties Biological properties Physicochmeical Properties it is generally accepted that the best drug candidates for passive adhesive transdermal patches must be; Non ionic Low molecular weight Adequate solubility in oil and water. Low melting point (less than 200 o ) Potent (dose is less than 50mg per day and ideally less than less than 10mg per day)

19. Biological Properties The drug should be potent with a daily dose of order of few mg/day. The half life of the drug should be short. The drug most not induce a cutaneous irritant or allergic response Drugs degraded in the GIT or inactivated by the hepatic first pass are suitable candidates for transdermal drug delivery.

20. Permeation Enhancers These are compounds which promote skin permeability by altering the skin as a bearier to the flux of the desired penetrant. Classification of Enhancers Solvents Surfactants Binary systems Miscellaneous chemicals

21. Other Excipients Adhesives; the fastening of the transdermal device is usually done by the adhesive. The adhesive should satisfy the following. Do not irritate or sensitize the skin Adhere to the skin during the dosing interval It should be easily removed. It should not leave any unwashable residue. The face adhesive system should satisfy the following criteria: It should be physically and chemically compatible with the drug, excipients and the enhancers. The delivery of the permeation enhancers should not be affected. Polymers used in the adhesives are polyisobutylenes , acrylic and silicones.