Transdermal Flashcards
Explain the Skin structure:
Dead Layer: Surface scale, outside hair, and nail
Living Layer: Viable epidermis (100-150
µm), dermis, subcutaneous + structures found within (blood vessels, sweat glands)
the different layers represent different stages of keratocytes in their development
What is the outermost layer?
Stratum corneum (dead layer or horny layer - 10-15 µm)
-scale-like dead keratinocytes or corneocytes (made of the protein keratin) tightly packed and thereby building a barrier; in between corneocytes there are lipids -> only drugs with a certain property or log P can cross the barrier
-relative acidic (acid mantle), around pH 5 maintained by sebaceous fluids
What is beneath the Stratum corneum?
The viable Epidermis: Stratum lucidum, granulosm, spinosum, basale (100-150 µm) -> they are constantly replenishing
-no nerves or blood vessels -> no sensation or bleeding
-envelope: controls the amount of moisture lost
-keratinocytes (cells that make keratin), melanocytes (making the pigment), and other specialized cells
Which layer is only found in palms and souls?
What is the layer of transition?
-Palms and Souls: Stratum lucidum
-Between dead and living layer: Stratum granulosm (Layer of transition)
What is the prickly layer?
Where are melanocytes and pigmented cells located?
-Live prickly layer: Stratum spinosum -> contains keratinocytes
-Stratum basale: contains melanocytes
Content of the dermis and Subcutaneous Layer:
-Dermis: connective tissue, nerves, collagen and
elastin fibers, blood, lymphatic vessels, and appendages (hair follicles, sweat glands, sebaceous glands)
-Subcutaneous Layer: consists of lipocytes, arranged as fat lobules, most of the body fat (80%) in this layer -> insulation from cold, endocrine function
Definition of Transerdemal DDS:
-Topically administered, long-acting medicated DDS designed to achieve systemic therapeutic effects
Applications of TDDS:
▪ Birth Control
▪ Cessation of Smoking
▪ Coronary Heart Disease and Angina
▪ High Blood Pressure
▪ Hormone Replacement
▪ Menopausal Symptoms
▪ Pain
▪ Motion sickness
▪ Schizophrenia
What are the advantages of TDDSß
-Bypass first-pass metabolism, no drug degradation/ irritation in the GI
-Sustained drug delivery, and can be stopped anytime
-patient compliance, clinician not required
-Non-invasive, can be given to unconscious patients, alternative route
Name an example of TDDS:
Diclofenac Gel for joint pain -> can cause GI irritation, and GI ulcers long-time
-no risk of bleeding GI-ulcers, renal impairment, and hypertension
-but systemic absorption is possible
What are the limitations of DDS?
-Major barrier for hydrophilic and large MW drug -> log P: 1-3, MW <500 Da, and MP < 250°C for passive permeation + no charged/ionic drugs for passive diffusion
-no high-dose drugs
-irritating to the skin and potential allergic reactions (skin rashes)
-Limited time of affixation, + Variable adhesion to different skin types
-Variable percutaneous absorption efficiency (skin type, placement tissues)
-Bacterial and enzymatic drug metabolism under the patch
-Complex technology/high cost
Characteristics of the ideal TDDS?
-MW < 500 Da (large molecules like protein drugs with long AA chains)
-log P 1-3 (under 1 is too hydrophilic, greater than 3 too lipophilic (f.e. steroid drugs, Estradiol) and gets stuck in stratum corneum)
-potent: <50mg/day -> too high dose is not possible
-Short half-life (<10hr) -> with Transdermal the drug doesn’t have to be taken as often
-Non-irritating and non-allergenic
Important Characteristis of Transdermal DDS
Delivery of a constant rate of drugs per hour
f.e. Fentanyl Patch: constantly12mcg/hr
-Onset is slow: f.e. Daytrana, therapeutic effect after 2h, needs to be removed after 9h, there still will be drug in the skin that is going to be delivered after removing the patch
Transdermal Patches:
-designed for sustained drug delivery
Matrix/Monolithic
Matrix/Monolithic:
-Top: Backing layer
-Adhesive matrix: drug either dissolved or dispersed in an organic-based pressure-sensitive adhesives
-Release liner: protection from air or water
->Skin-controlled Drug release bc there is no membrane controlling the rate of release: Single-layered (1 layer of drug), Bi-layered (2 layers of drug)
CAN IT BE CUT??
->System-controlled Drug Release contains a rate-controlling membrane:
Multi-layered -> Backing layer -> Drug layer -> Rate- Controlling membrane -> skin contact membrane -> Release liner
CANT BE CUT!!
Why should the System-controlling Patch never be cut?
The patch is losing its ability to release the drug at a constant rate
