Percutaneous absorptionMs.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

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).

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.

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 portioncomposed of keratinized stratified squamousepithelial tissue.

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-keratinocytes2-melanocyets3-langerhans cell4-merkel cell.

Percutaneous Absorptionkeratinocyteskeratino=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.

MelanocytesMelano=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

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.

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.

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

Percutaneous AbsorptionAppendages of the skin:• Hair follicles with hair• NailsGlands of skin:• There are two types of glands • Sweat glands• Sebaceous glandsSebaceous 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.

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

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.

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

Percutaneous Absorption

FACTOR AFFECTING PERCUTANOUS ABSORPTION:

BIOLOGICAL PARAMETERS:• Skin condition• Skin age• Blood flow• Regional skin sites• Skin metabolism

Percutaneous AbsorptionPHYSICOCHEMICAL 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

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