1. Percutaneous absorption Ms.Wajiha Iffat Objective: After the end of this lecture, student will be able to : Describe Structure of skin define the percutanous absorption Its importance Factor affecting percutaneous absorption Ways to maximize drug bioavailibility

2. Percutaneous Absorption Skin also known as cuteneous membrane or integument. It means any external membranous covering or integument of an animal body. Skin is the largest organ of the body,it is thin at some places (eye lids thickness =0.5mm) where as thick at other places (sole of foot, palm of hand thickness=5mm). Average thickness of skin is 1-2mm.(0.04- 0.08in).

3. Percutaneous Absorption In adults, the skin covers an area of about 2 square meter and weight 4.5-5kg, about 16% of total body weight.

6. Percutaneous Absorption Skin is made up of two layers, 1.Outer epidermis, 2.Inner dermis. 1:-Epidermis epi =above, dermis=skin It is the superficial, thinner portion composed of keratinized stratified squamous epithelial tissue.

7. Percutaneous Absorption Epidermis replaces itself. about every two and half months. It has no blood vessel but it is nourished by diffusion of nutrients from a vascular network of dermis. It is composed of 4 type of cells 1-keratinocytes 2-melanocyets 3-langerhans cell 4-merkel cell.

8. Percutaneous Absorption keratinocytes keratino=horn like, cytes=cell 90% of epidermal cells are keratinocytes. These are arrange in 4 to 5 layers and are responsible for production of protien keratin,which is a tough fibrous protein responsible to protect the skin and underlying tissues from heat, microbes and chemical. Melanocytes Melano=black, cytes=cell 8%of epidermal cells are melanocytes. They produces a pigment melanin (a yellow red or black brown pigment) contribute in skin colour and also absoorbs damaging u-v light

9. Percutaneous Absorption Langerhans cells They participate in immune responses against microbes that invade the skin and they are easily damaged by u-v light. Helps other cells of immune system to recognize an invading microbe and destroy it. Merkel cell Participate in detection of touch sensation.

10. Percutaneous Absorption DERMIS : The sensitive connective tissue layer of the skin located below the epidermis, containing nerve endings, sweat and sebaceous glands, and blood, hair follicles, fibroblast, histocytes and lymph vessels. Also called corium, cutis, Also called derma. Composed of strong connective tissue containing collagen ( for strength ) and elastin ( for stretch ) Derma blood vessels not only supply blood to the dermis and epidermis but also play major role in temperature regulation.

11. Percutaneous Absorption Hypodermis : Below the dermis is hypodermis also k/as subcutaneous layer Sub mean under and cutaneous mean skin. It is a loose layer of connective tissue which is anchored to the underlined tissue ( muscle and bones). Most fats cells are present in hypodermis collectively known as adipose tissues act as insulator to protect the body from excessive heat and cold environment

12. Percutaneous Absorption Appendages of the skin: Hair follicles with hair Nails Glands of skin: There are two types of glands Sweat glands Sebaceous glands Sebaceous glands : They are simple or branched alveolar glands situated in the dermis of skin They secrete an oily secretion c/as sebum active at the time of adolescense.

13. Percutaneous Absorption Percutaneous Absorption: Percutaneous absorption involves the transfer of drug from skin surface in to stratum corneum, under the aegis of a concentration gradient and its subsequent diffusion through the dermis and in to microcirculation the skin behaves as a passive barrier to diffusing molecules

14. Percutaneous Absorption Percutaneous absorption of a drug generally results from the direct penetration of the drug through stratum corneum,10-15µm thick layer of flat partially desiccated non living tissues. SC is composed of 40%protein & 40%water with a balance being lipid. SC acts as a semi permeable membrane & drug molecules penetrates by passive diffusion. it is the most rate limiting barrier to TDDS TRANSPORT.

15. Percutaneous Absorption RATIONAL APPROACH TO DRUG DELIVERY TO & VIA THE SKIN: Surface treatment Strarum corneum treatment Skin appendage treatment Viable epidermis & dermis treatment Systemic treatment via transdermal absorption

16. Percutaneous Absorption FACTOR AFFECTING PERCUTANOUS ABSORPTION: BIOLOGICAL PARAMETERS: Skin condition Skin age Blood flow Regional skin sites Skin metabolism

17. Percutaneous Absorption PHYSICOCHEMICAL PARAMETERS: Physicochemical Attraction Of Drug Mol Wt Of Drug Hydration Of Skin Temperature & pH Drug Concentrations Diffusion coefficient Partition coefficient Area Of Applications Contact Time

18. Percutaneous Absorption MAXIMIZING THE BIOAVAILIBILITY OF DRUG TO SKIN: Drug or pro drug selection Hydration Ultrasounds(phonophoresis) Ionophoresis elctroporation Stratum corneum removal Microneedle array Chemical penetration enhancers