M8. Percutaneous absorption Flashcards
permeation of drug molecules across the skin
Drug permeation is governed by diffusion: Fick’s law applies → conc gradient will determine diffusion properties
- main rate limiting factor for drug diffusion= stratum corneum followed by a series of partitioning steps from one layer to the next
- Highly hydrophobic drug molecules can form a depot in the SC or in the dermis eg. corticosteroids
- drugs can be metabolized in the viable epidermis and dermis: can decrease effect OR could be used for a prodrug approach
target site for topical delivery v transdermal
- Topical delivery: target site is the skin
- Transdermal delivery: target site is the systemic circulation
what are the routes of percutaneous absorption
- Across stratum corneum
- brick and morar model of stratum corneum
- corneocytes (keratin filled dead cells), lipids glue them together
- forms a lipid bilayer
- Via Appendages (drugs penetrates throuhg pores of the skin0
- sweat ducts
- sebaceous glands
- hair follicles
*
What are the drug factors that influence percutaneous absorption
- conc of drug in the preparation (provide a hgih conc gradient across skin)
- partition coefficient (hydrophilicity/hydrophobicity)
- Vehicle-to-stratum corneum partition
- ratio of conc. drug in stratum corneum to the conc. drug in the vehicle
- Kp (permeability coefficient) large: INC paritioning
- drug/skin binding
Vehicle facotrs affecting percutaneous absorption
- pH -> determines ionizaition of the drug
- co-solvents -> concentrate drug on skin
- release of drug from vehicle -> optimize with appropriate vehicle
- penetration enhancers temporarily increase permeabiltiy of the skin (enhance percutaneous abs
**want unionized form bc more hydrophobic, good for compounding
skin factors that infleunce percuraneous abs
age of the skin (children vs. adults)
skin condition (e.g., hydration of stratum corneum, disease state)
thickness of stratum corneum (regional skin sites eye area is permeable; back is relatively impermeable)
skin metabolism
circulation effects
species differences (animals vs. humans)
What are topical corticosteroids
- contain derivates of natural corticosteriod hormones
- applied to skin for localized treatment of inflammatory skin conditions
- hydrocortisone = backboens tructure of most topical corticosteroids (not very potent itself)
- can alter functional groups
- removal or replacement of hydrozyl groups can change lipohliicty, solubility and percutaneous abs
what factors influence topcial corticosteroid absorption kinetics
- concentration of corticosteroid used
- hydration
- application to hydrated skin after bathing can increase abs
- occlusion
- ex plastic wrap, esp in case of severe lesions
- other factors
- can incorporate the drug into two preparations
- one with propylene glycol or urea and salicylic acid (penetration enhancer) to get high potency produc
- mixing baes
- can increase or reduce potency and shelf life
- can incorporate the drug into two preparations
how are topical corticosteroids classified
- according to relative potencies
- class I: ultra high potency
- have greater anti inflammrort actiivty with higher risk of side efects
- used for severe dermatoses on non facial and nonintertrigenous areas (scalp, palsm, soles and thick plaques)
- ex use for psoriasis and where areas of skin penetration are poor
- Classes II-V: med- high potentcy
- used for mild -> moderate non facial and nonintertriginous areas
- class VI-VII: lowest potency
- areas where penetration is high (face, eyelid, axilla, genital and intertrigous)
- used in young childran, infants and elderly
- recommended inc ase of long term therapy or to large areas
what does the calss of a corticosteroid determine?
potency
not the % concentration
- potency within a class is influenced by formulation: ointment>ream > lotion > gel > foam/spray/solution
ointments as topical corticosteroid vehicles
- more effective bc of occlusive nature
- preferred in treating chronic lesions (psoriasis) or young children with infantile atopic dermatitis where dryness of the skin is a particular problem
- should not be used in areas such as the axilla, groin, or skin folds due to their occlusive effect and high risk of corticosteroid side effects
creams as topical corticosteroid vehicles
preferred for non-acute dermatoses bc cosmetically more acceptable
proper application requires rubbing fully into the skin in such a way that a residue is not visible after application
lotions as topical corticosteroid vehicles
non-occlusive, easy to apply
useful when large skin areas or skin flexures are affected
Some lotions, such as scalp lotions, are suitable for hairy areas
Gels as topical corticosteroid vehicles
non-greasy, non-occlusive, non-staining, and quick drying
most useful when applied to hairy or facial areas where residue from a vehicle is unacceptable
Foams, sprays and solutions as topical corticosteroid vehicles
non-greasy, non-occlusive, non-staining, and quick drying; if contains alcohol it can be very drying and can sting sore skin
used on scalp and hairy areas
localized side effets of topical corticosteroids
- Skin atrophy
- Usually occurs after several weeks of treatment.
- Reversible within 2 months (sometimes longer)
- Striae
- Most common around the groin, axillae, and inner thigh
- Usually not reversible may fade over time
- Telangiectasia:
- Visible distended capillaries. Often seen on the face, neck, chest. Usually reversible, but can be permanent
- Purpura:
- Bruising with minimal trauma
- Fine hair growth
- , hypertrichosis
- Acne like eruptions:
- Common on the face, reversible
- Hypopigmentation:
- Especially in dark skinned people Rebound dermatitis: occur with sudden discontinuation Mask fungal infections
dosing of topical corticosteroids
FTU- figner top unit
*qty of topical medication dispensed from a 5 mm nozzel placed on a pad of index finger
- 4 hand areas on body = 2 FTU units = 1 g of cream
* 1 FTU is enough to cover whole two palm areas
