Transdermal DDS Flashcards
What is the main barrier of the Epidermis?
Stratum Corneum; prevents endogenous substances and water loss
Shu bi2alba el dermis
sweat, sebaceous glands, hair fllicles, nerves, blood vessels
what are keratinocytes
Dead cells bl stratum corneum
rate of Diffusion equation
m=(DKA/d) x (Cd-Cr)-t
(DK/d)=1/resistance=Permeability coefficient cm.sec-1
Total permeability= 1/Rvehicle + 1/Rsc + 1/Repi +1/Rdermis
What are the components of Resistance
Vehivle, Stratum corneum(aktr shi), Epidermis, dermis
Methods for measuring absorption through skin
In vivo blood studies, In vivo clinical efficacy studies, In vitro Human skin or artificial memberane
What are the biological factors affecting Drug delivery
Skin condition
Skin age
Regional Skin sites ( behind the ear aktr shi)
Blood flow ( increase bld flow = increase permeation
Skin metabolism
Physicochemical Factors
Skin hydration= kl ma aktr kl ma ahsn
Temperature= more fluid more permeable
pH of vehicle= ionized cross aktr
Diffusion Coefficient
Drug concentration
Partition coef
Mioecular size
What are the approaches used
Biochemical
Chemical
Physical
Formulation
Biochemical approach uses what?
Bio-convertible products (prodrugs) with better permeation profile e.g. theophylline
Also the co administration of skin metabolic products
What does the Chemical approach use?
Penetration enhancers that temporarily diminishes the impermeability of the skin
E.g. Of penetration enhancer that acts by improving solvent property of SC
urea (for skin hydration)
E.g. Of penetration enhancer that acts by Disrupting lipid matrix of SC
Dimethylsulfoxide (DMSO) and Azones
E.g. Of penetration enhancer that acts by Promoting partitioning
Propylene glycol
What are the 3 mechanism Penetration enhancers can act by:
Improving solvent properties (skin hydration)
Disrupting lipid matrix
Promote partitioning
What is an advantage of physical approach
Active transdermal drug delivery used to overcome limitation of previous techniques and deliver problematic drugs
E.g. of problematic drugs:
High conc of ionic molecules
Large molecular weight
High doses drugs ( low potency)
What are the physical approaches:
Stripping SC
Sonophoresis
Electronporation
Iontophoresis
Microneedles
How can the SC be removed
By the use of adhesive tapes
mechanical dermal abrasion
Laser
One disadvantage of SC stripping
Costly may cause skin damage
What is Sonophoresis
Use of ultrasound energy can lead to
Cavitation
Heating
What is cavitation and heating
Cavitation: leads to formation of holes, enlargement of intercellular spaces and perturbations of lipid SC
Heating: increases fluidity of SC and the diffusivity of molecules
What is Electroporation
The creation of aqueous pores in the lipid bilayer by the application of short electrical pulses ( micro to millisecond) of large voltage
What is Iontophoresis
Charged Molecules (ions) are forced through the SC by the use of small voltage electro repulsion
Drug diffusion is proportional to the current density
What is Micro needling array
Minimally invasive technique
SC is breached without pain using a device consisting of microneedles to insert the drug just below the barrirer without stimulating nerves in deep tissue
Deghre btusal aal dermis
Flux may increase by 1000 folds
4 types of microneedles
Solid removable: Drug free
Coated: Medicated; When the needle is inserted into the skin, the coating dissolves and releases the drug into the skin. Coated microneedles are often used for transdermal drug delivery, vaccination, and other medical applications.
Dissolving; dissolve in the skin, delivering a drug or other substance as they dissolve
Hollow; small hollow channel running through its center. This channel allows a drug or other substance to be delivered directly into the skin, bypassing the outer layers
What is formulation approach
Uses colloidal carriers i.e nanoemulsions
E.g. of colloidal carriers
Liposomes; 3andon lipid bilayer enclosing aqueous core
Nanoemulsion; lipid monolayer lipid cre
Solid lipid nanoparticles; lipid monolayer solid lipid core
Transdermal Patches
Multilayer polymer based
Two types
matrix and reservoire
Matrix Controlled Transdermal Patch Consists of
Impermeable occlusive baking layer
Core polymer matrix
Adhesive Layer
Release Liner
Impermeable occlusive baking layer
non absorptive, printable
i.e. Vinyl Polyethylene, polyester
Protection and promotes hydration
Core polymer Matrix
Contains drug with permeation enhancer to control release
i.e. HPMC, polymethylmethacrylate, Eudragit
Sustained release
Adhesive Layer e.g.
Polyacrylate
Polyisobutylene
Polydimethylsiloxane
(Prolonged Duration)
Release liner e.g.
Polyester
Styrene based films
( removed mtl plaster)
Matrix controlled is thin or thick?
What drugs are most appropriate
Thinner that reservoir
Appropriate for drugs that penetrate more readily and/or have low dose regimen
Reservoir Controlled; What does it consist of
Impermeable occlusive baking layer
Reservoirof gel containing drug and permeation enhancer
Rate controlling membrane; i.e. microporous PP or PE membrane
Adhesive Layer
Release Liner
When is Reservoir controlled used
used when Matrix system cannot penetrate skin
Drug require high penetration enhancement or high dose level
E.g. of Marketed Transdermal patches
Clonidine for ADHD
Estradiol
Fentanyl=Opioid
Nicotine for Smoking cessation
Oxybutynin= Antimuscarinic for urination control
