Transdermal Drug Delivery Flashcards
Opportunities for skin delivery
Avoids issues with GI transit and first pass metabolism
Controlled/easily terminated
Companies can introduce transdermal products to extend the life cycle of products
Local delivery of dermatological and cosmeceutical products
New opportunities of passive and active technologies for local and systemic delivery
Why is skin an attractive route of delivery?
Skin protects us, warns us, maintains us and defines us
Skin is plentiful, readily accessible and can be monitored easily
Suitable portal for both local and systemic therapy (not first pass)
Drug delivery can be targeted, controlled and sustained
Effective and convenient for most
Potential benefits of transdermal delivery
Reduced dosage frequency
Improved patient acceptance (no needles), convenience (self-administration) and compliance
Sustained therapeutic action
Reduced first pass effect and GI incompatibility
Diminished side effects
More consistent delivery of drug
Retrievable dosage form that facilitates termination of dosing
Limitations of transdermal delivery
Only suitable for certain molecules (potent and permeable)
Skin irritation
Lag time
Cost
Direct trans-cellular path through stratum corneum
Solutes permeate directly across the stratum corneum, repeatedly partitioning between the lipophilic intercellular space and the hydrophilic corneocyte, passing across the cornified cell envelope
Biological factors affecting transdermal drug delivery
Age
Race
Cutaneous metabolism
Skin permeation
Most important determinants of rate and extent of permeation across skin are:
Skin/vehicle partitioning
Diffusivity through the stratum corneum
Most important attributes of a skin permeable molecule are:
Daily dose <10-20mg/day Half life 10 hours or less Molecular weight <500 daltons Melting point <200c Partition coefficient LogP 1-3 Non-irritating and non-sensitizing
Major limitations of models for predicting the permeability coefficient
The models are based on permeation from simple aqueous solutions
Physiological factors are not considered
Formulation effects are not considered
Competing processes
Competing processes can significantly modify the degree to which material within the SC is ultimately absorbed
Metabolism, exudation, abrasion, desorption, desquamation, washing
What molecules already work?
Scoploamine- motion sickness
Nitroglycerine- anti-angina
Clonidine- hypertension
Nicotine- smoking cessation
Estradiol +/- progestin, testosterone- HRT
Fentanyl, lidocaine, buprenorphine- pain management
How can we help molecules permeate?
Modify drug- improve properties Increase driving force- modify formulation Aid diffusion- loosen cells Alter partition- soften lipids Metabolise prodrug- change properties Increase clearance- induce vasodilation
Hair follicle permeation
Surface area of follicle wall much greater than area of follicle orifice, increasing area available for permeation into epidermis and dermis
Dense capillary networks around base of both hair follicles and sweat ducts provide good systemic access for most molecules that can permeate to those regions
Penetration enhancers
Work by:
Causing reversible damage to the SC (disrupt packing of the lipid bilayers)
Optimising thermodynamic activity of drug in the vehicle and/or skin
Increasing drug diffusivity in the SC
Establishing a drug reservoir in the SC
Increasing solubility of the active
Examples of chemical penetration enhancers
Dimethyl sulfoxide and related compounds
Azone and related compounds
Solvents and related compounds
Fatty alcohols, fatty acids and related structures
Fatty acid esters
Should be non-toxic, non-irritating and compatible
