Pharm 734 Final Flashcards
Topical Drug Delivery: Action, Uses
Local Action Only
- Protect injured areas of skin
- Hydrate skin
- Local therapeutic effect
Layers of Skin Anatomy
Epidermis
Dermis
Hyperdermis
Epidermis Features
0.006 to 0.008mm thick Stratum Corneum (outermost layer, 10-20% moisture)
Dermis Features
3-5mm thick
matrix of connective tissues, woven fibrous proteins, nerves, blood vessels
Hyperdermis Features
Subcutaneous Tissue
Mechanical cushion, thermal barrier, energy storage
Skin Appendages
Hair Follicles
Sweat Glands
Sebaceous Glands
Nails
Drug Travel Path from Skin (Cream, Gel, Lotion, Patch etc)
Skin Surface –> Stratum corneum –> Viable Epidermis –> Dermis –> Blood Circulation
Epidermis Layers and maturation
Stratum Basale (bottom, Hydrophilic)
Stratum Spinosum
Stratum Granulosum
Stratum Corneum (Top, Hydrophobic)
Protective Function of Skin
- Microbiological Barrier
- Chemical Barrier
- Radiation Barrier
- Heat/Temperature Regulation
- Immune response
Targeted Region of Topical Drug Delivery
Surface Treatment (e.g. insect repellant, sunscreen) Stratum Corneum (Emolient, Keratosis) Skin Appendage (Acne, Antibiotics, Antiperspirant) Viable Epidermis/Dermis (antihistamine, anesthetics)
Skin Problems at Different Regions of skin
Stratum Corneum (Psoriasis, Dry Skin) Viable Epidermis (Eczema) Dermal/Epidermal interface (warts) Dermis (scarring) Hair Follicle/Sebaceous/Sweat gland (Hirsutism, Acne, Heatrash) Other (Fungal/Athlete's foot)
Topical Dosage forms
Semi-Solids
Solids
Liquids
Semi Solid topical forms
Ointments Creams Pastes Gels Jelly
Solid topical forms
Powders
Aerosol
Plaster
Liquid topical forms
Solutions Emulsions Suspensions lotions Liniments Aerosols
Advantages of Topical Drug Delivery
High drug concentration at site of application
Low risk of systemic side effects
Non-Invasive
Easy to Use
Disadvantages of Topical Drug Delivery
Contact time for drug is limited Ointments and creams are messy to use Potential for systemic absorption formulations can cause skin irritation Difficult to measure exact dose Rubbing, Heat, Exercise inc systemic absorption
Semi Solid Dosage Forms (applications)
Intended for topical application Medicated or non-medicated Emolient (softens skin, no absorption) Protective (protects skin against environment) Vehicles
Antipruritics
Relieve Itching of Skin (menthol, Camphor, coal tar)
Keratolytics
Remove/soften the thickened or scaly stratum corneum
Antieczematous agents
Assist in removal and treatment of oozing and vesicular excretions.
Antiparasitics
Destroy or inhibit living infestations
Antiseptics and Antibiotics
Bacteriostatic, bactericidal, fungistatic, Fungicidal
Antiseborrheics
Reduce discharge from sebaceous glands and remove symptoms
Types of ointment bases
hydrocarbon (oleaginous)
absorption bases
emulsions (W/O and O/W)
Water-miscible bases
Gels are:
3D network of inorganic molecules and large organic molecules in a liquid
Water-washable
Drug is dispersed/dissolved in water or a water/ethanol mixture in gel
Rate of drug release is usually fast
Sunscreen gels, gel for anti-fungal and anti-inflammatory
Pastes are:
A large proportion of solid material than ointment, not less than 20% solid
Less greasy than ointment
Pastes are stiffer than ointments
Good for absorption of secretions
Not good for application to hairy areas due to stiffness
Not water washable
Creams and Lotions are:
Homogenous semi-solid preparations consisting of opaque emulsion systems.
Consistency and rhelogical properties depend on the type of emulsion.
Creams can contain one or more medicinal agents dissolved in W/O or O/W
O/W cream and water = Lotion
What physiological factors affect drug penetration
Thickness of SC
Condition of SC
What drugs can cross skin? (how can drug diffusion be increased?)
Small hydrophilic polar molecules
Small hydrophobic molecules
(Decreasing MW, Occluding the skin, damage to skin)
What is required for Drugs to penetrate SC?
Drug dissolved in base
Drug diffuse to surface of skin
Drug must partition into SC
Drug must diffuse to site of action in epidermis
How can Drug penetration be increased?
Higher Drug Concentration
Thicker Layer of Ointment
Larger Surface Area
What is Levigation?
The process of reducing the particle size of a solid by triturating it with small amount of liquid or melted base to wet the solid
What are Humectants?
Ingredients that attract water (Glycerin, PEG, urea, lactic acid)
Pulls water into SC from deeper layers
Prevents drying of o/w creams/lotions
What are Astringents?
Substances that control oozing, discharge or bleeding
Coagulate Protein, acts as protective coat, allows new cells to regenerate underneath
Used for “weeping” wounds
(E.g. Gallic Acid, Aluminum Sulfate)
Topical Patches (NOT transdermal)
Intended for local action at skin
E.g. Diclofenac
Nails
100x thicker than SC
very impermeable to topical drugs
Difficulty in retaining formulation on nail
Occlusive covering helps penetration
Transermal Drug Delivery Systems
Facilitate the passage of therapeutic quantities of drug substance through skin into general circulation for systemic effect
TDDS Advantages
Bypass Hepatic "First Pass" Bypass GI Incompatibility Reduced Side Effects Greater Compliance Minimize Inter/Intra patient variation Terminate therapy by removing patch Etc.
TDDS Disadvantages
permeation through skin limited
Skin irritation
patches uncomfortable
May not be economical
TDDS Drug properties
- Drugs w/ Short Hal-life
- Proper lipophilicity/hydrophilicity
- low molecular weight (~100-500 Da)
- Potent drug (narrow therapeutic window)
- should not bind extensively to skin
- should not be irritating to skin
- clinical necessity for steady state delivery
- drugs can be subject to high 1st pass
Layers of Epidermis
Stratum Corneum
Stratum Granulosum
Stratum Spinosum
Stratum Basale
Epidermis Notable Facts
- Turnover ~28 days (14 days dehydrate, 14 days shed)
- Avascular
- Stratum Corneum most important barrier
Dermis notable features
- Rich blood supply, lymphatic vessels and nerve endings
- Drugs quickly diffuse
- Collagen fibers (structural strength)
- Elastin FIbers (Elasticity)
Fick’s Law of diffusion in TDDS
J = Pe x Co J = Flux, movement of mass/area/time
TDDS LogP target zone
1-4 (partition coeffecient)
Construction of TDDS
- Impermeable Backing membrane (occlusive)
- Drug Reservoir/ Matrix
- Rate-controlling membrane
- Adhesive Layer
- Protective Liner
