PHA 327-Transdermal Systems
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What are concentration dependant mass transfer systems that are commonly used?
What is M in the definition of flux?
The grams of material flowing through a cross-sectional area in time t
What are the Units for C1 and C2 in Fick's law of diffusion?
What are the units for the Diffusion Coefficient?
What is D a function of (5)?
- Solvent properties
- Chemical nature of the solute
Why is Fick's law important in pharmaceutics?
- Creation of Controlled release dosage forms
- Physiological phenomena
- Bioavailability of drugs
- Efficacy of Dialysis
What specific uses are common for Fick's Law?
- Design of transdermal systems
- Design of membranes for different release profiles
- Determination of Diffusion coefficient to predict bioavailability
What are the advantages of Transdermal delivery?
- Controlled delivery
- Less enzymatic breakdown
- No GI or hepatic first pass degredation/metabolism
- Local and systemic effects
What type of molecules are delivered transdermally?
- Peptide therapeutics
What is the outermost part of the skin?
Name the skin layers form outer to inner:
- Stratum corneum
What are the four routes of percutaneous absorption?
- 1.) Intercellular diffusion SC
- 2.) Transcellular diffusion through the SC (between cells)
- 3.) Diffusion through aqueous phase sweat ducts
- 4.) Diffusion through oil phase hair follicles
What is the equation of the Partition Coefficient?
Kp = Jss/Cv
What chemicals can enhance Percutaneous absorption (7)?
- Bile salts
- Dimethyl sulfoxide
- Propylene glycol
- Oleic Acid
What are the methods of enhancing percutaneous absorption?
How does Iontophoresis work?
- Two electrodes on skin
- Drug reservoir is at one of the electrodes
- Uses existing pathways but may affect skin morphology
What are the two types of Iontophoresis?
Cathodal and Anodal
What is electroporation?
- High voltage pulse of 100-400 DC per ms or us
- Creates tiny pores in the SC
What is another name for phonophoresis?
How does Phonophoresis work?
- Disorganizes the lipid bilayer, creating channels
- Ultrasound of frequency >50KHz is applied
- Creates air pockets in the cells and expands them
How is skin barrier function measured?
Transepidermal water loss
How does TEWL work?
- Microprocessor with two sensors that read temperature and moisture
- All in a cylindrical probe head
What measures skin captance?
What does a Corneometer read?
Inflammation has what effect on percutaneous absorption?
What is Acute uraemia?
Deposition of urea under the skin
What effect does Acute uraemia have on percutaneous absorption?
Decreases percutaneous absorption
Occlusive dressing enhance the percutaneous absorption of what?
What is a transdermal drug delivery system?
A controlled, predetermined delivery of a drug through the skin
What specific type of drugs are optimal for Transdermal systems?
- Short half lives
- Narrow therapeutic window
What are the four dosing and bioavailability benefits of Transdermal delivery systems?
- Concentration can be maintained within a narrow therapeutic window
- GI breakdown is eliminated
- No First pass effect
- Good for drugs w/ narrow therapeutic widows ad short half lives
What are the patient benefits of Transdermal delivery systems?
- Adherence is easier (less dosing)
- Self administration is easy
- Easy to stop therapy
- Hard to overdose
What physical factors affect the ability of a drug to be delivered transdermally?
- Melting point
What systemic drug factor prevents Transdermal administration?
Drugs that require a high plasma level
What are some of the factors that limit Transdermal delivery use?
- Irritation of drug to skin
- Drug binds to skin
- Too expensive
- Drug requires high plasma levels
What are the indications for using Transdermal delivery systems?
- Oral is contraindicated
- The GI is not working or not working consistently
What four things should you consider before formulating a drug transdermally?
- Kinetics of permeation
- Features of the skin
- Physio-chemical properties of the drug
- Features of the transdermal system
What are the steps in transdermal drug transport?
- Release of drug from the device
- Partitioning on the skin surface
- Diffusion and binding in the Stratum corneum
- Partitioning and binding to the SC and viable epidermis boundary
- Diffusion into and bioconversion of the drug in the viable epidermis
- Entry into the blood vessel
What are the four design types for Transdermal delivery?
What type of Reservoir type transdermal systems exist?
- Without rate limiting membrane
- With rate limiting membrane
What types of reservoirs without a rate limiting membrane exist?
- 1.) With a rate limiting membrane
- 2.) Microencapsulated drug reservoir
Give an example of a Reservoir type TDS that has a rate limiting membrane?
- Estraderm (Ciba)
Give an example of a Reservoir TDS without a rate limiting membrane that has a rate limiting adhesive layer:
- FrandolTM (isosorbide dinitrate)
- DeponitTM (nitroglyceride)
What are the parts of reservoir type TDS?
- Backing, Drug reservoir, Control membrane, Adhesive layer, Protective peel strip
What is a Matrix type device?
Drug is dispersed through a hydrophobic or lipophilic membrane molded into a certain size
What is an example of a Matrix TDS?
Nitro-Dur (Key Pharm)
What is a Microsealed drug delivery system?
- A mixed system
- Incorporation of microdispersion in spheres of matrix
What is an example of Microsealed Drug delivery systems?
What type of TDSs are Mixed systems that utilize both Matrix and Reservoir systems?
What are Poroplastic TDSs?
Ultramicroporous cellulose triacetate membranes
What types of Poroplastic TDSs are out there?
- Simple monolithic
- Zero-order monolithic system
- Distinct reservoir system
Name the five established drugs for Transdermal delivery?
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