P11, P12 & P13: Topical Drug Delivery Flashcards
what is the structure of the stratum corneum
bricks= dead keratin-filled cells
mortar= complex lipid mixture
has rivets holding corneocytes together are specialised protein structures called corneodesomes
what are corneodesomes
major structures to be degraded for desquamation of the skin
what are the pathways through the stratum corneum
transcellular
intercellular
via which pathway does H2O cross the stratum cornea
intercellular
what is the drug/delivery system supposed to do
modulate barrier function, treat disease states in the epidermis an dermis, alleviate local pain/inflammation in subcutaneous tissues, elicit systemic pharmacological effect
where is the therapeutic target and how accessible is it
surface, stratum corneum, viable epidermis/dermis, skin appendages, suncutaneous tissue, systemic circulation
what happens during percutaneous absorption
absorption of drugs from the skin surface into the body
drug penetrates into skin and is taken up by microcirculation
what does percutaneous absorption depend on
physiochemical properties of a drug, interactions of drug with vehicle or delivery system and with the skin, condition of the skin
how are topical formulations optimised
many are lipophilic with very low aqueous solubility
introduction of co-solvent into a formulation can increase Csat but this has the opposite effect on Ksc/v
how does pH of vehicle influence absorption
skin surface pH is acidic
unionised drugs best absorbed
extreme pH values damaging to skin, formulations mostly neutral
how does skin permeation affect absorption
some excipients, when incorporated in wehicle, can improve drug flux, but correlation between enhancement efficacy and skin irritation produced
what is the ideal vehicle in drug formulation
elicits no pharmacological effects, solubilises the drug, releases the drug with appropriate kinetics, is chemically and physically stable, is cosmetically appealing, is non-allergenic and non-irritating
what are the issues during drug formulation
interaction of vehicle with skin, interaction between drug and vehicle, no ‘rules’ for matching a formulation to a particular drug, enhancing delivery without irritating the skin
what physiochemical considerations need to be made during drug formulation
MW, lipophilicity, H-bonding, solubility in different solvents
how are formulations selected
type of emulsion, lipid content and occlusivity
what type of formulation is preferred for chronic skin disease
hydrocarbon-based formulations
how can drug solubility be enhanced
by formulation with hydrocarbon-miscible solvents like isopropyl myristate or propylene glycol
what is the water-free PEG-gel formulation
polar, 1-phase, semi-solid system, based on polyethylene glycols
what is the water-free lipogel formulation
polar, 1-phase, semi-solid system, principally based on triglyceride derivatives
what is the water-free oleogel formulation
polar, 1-phase, semi-solid system compromising triglycerides and/or hydrocarbon/ silicon oils and inorganic filter
what is the water-free fatty ointment formulation
apolar, 1-phase, semi-solid system, based on hydrocarbon materials
what are water-free formulations used to treat
psoriasis, chronic eczema, mycosis
small area of application to very dry skin
what is the base for polar gel formulations
water and/or alcohol-based with low lipid content or even lipid free
variety of gelling agents for thickening solutions and suspensions, allowing creatino of diverse formulations
what is an emulsion gel
hydrogel containing a dispersed lipid phase
what are suspension gels
suspensions of water-insoluble drugs in hydrogels
what is hydrogel
semi-solid system, typically compromising large organic molecules inter-penetrated by water
what is emugel
2-phase system, consisting of large organic molecules inter-penetrated by water and small fraction of emulsified lipids
what are gel formulations used to treat
acne, acute eczema, allergic skin conditions
small application areas to normal-to-oily and inflamed skin, transparent to opaque semi-solid gels, rapidly absorbed
what are emulsions
creams, disperse systems and the majority of aqueous formulations
readily adjustable properties, require emulsifiers
what are the features of w/o emulsions
blend easily with SC lipids, improving bioavailability of lipid-soluble drugs and moisturising skin via slight occlusive effect
what are the features of o/w emulsions
more cosmetically appealing as lipids therein are finely dispersed
can withdraw moisture from the skin due to surfactant-like emulsifiers
what is w/o lotion
hydrophobic, semi-liquid, 2-phase system, compromising water and a continuous lipid phase
what is w/o cream
hydrophobic, semi-solid, 2-phase system, compromising water and a continuous lipid phase
what are w/o creams used to treat
psoriasis, chronic eczema, mycosis
broad areas of application to normal to dry skin
what is o/w cream
hydrophilic, semi-liquid, 2-phase system, compromising lipids and a continuous aqueous phase
what is o/w cream
hydrophilic, semi-solid, 2-phase system, compromising lipids and a continuous aqueous phase
what are o/w creams used to treat
acne and acute and sub-acute eczema
broad areas of application to normal to slightly dry skin and to inflamed areas
what is the absorption base of dermatological formulations
apolar, 1-phase, semi-solid system compromising mainly hydrocarbon structures
what is the liposome formulation
bi- or multi-lamellar phospholipid structure entrapping a hydrophilic core
what are nanoemulsions
vesicles of phospholipids, surfactant and other lipid dispersed un water
what are microemulsions
transparent o/w or w/o colloidal emulsions compromising lipophilic and hydrophilic surfactants and water
what are emulsifier-free systems
2-phase, semi-solid and hydrophilic, comprising various lipids, a continuous aqueous phase and polymers/co-polymers
what are multiple emulsions
3-phase, semi-solid, hydrophilic (w/o/w) or hydrophobic (o/w/o) systems
what are spray emulsions
stable, sprayable, 2-phase, semi-liquid emulsions
what are foam/mousse formulations
gas dispersions in liquids containing lipids and water stabalised with surfactants
what are water-free 2-phase systems
physical mixture of 2 non-miscible organic phases forming semi-solid stabalised with polymers/co-polymers
what are lacquers
polymeric film-builders in volatile solvents and plasticiser leaving transparent, elastic and adhesive film on skin/nail
what happens to formulations when they are applied to skin
structural matrix of formulation may change due to rubbing or loss of volatile excipients leading to increased viscosity
rubbing may cause emulsifying effects
