michniak transdermals and topicals

physicochemical properties of skin

- there is a water gradient, calcium gradient, and pH gradient

- more lipophilic and acidic towards the surface of the skin

differentiating between topicals and transdermals

- distance from surface to get to target site

- topicals applied to unhealthy skin

- transdermal must be healthy to apply

- ingredients that could further irritate already affected skin

- in vitro release, penetration testing, and clinicals

dosage forms used for topicals

- ointments and creams

- lotions, pastes, collodions, powders

- plasters, tapes, gauzes

- solution, tinctures, liniments, hydrogels

- liposomal preparations, microemulsions, nanoemulsions

topical delivery: site

- deeper is more challenging to get to; run the risk of drug being picked up into systemic circulation

- top of stratum corneum

- stratum corneum

- epidermis

- dermis

- combination of epidermis and dermis

- known are percutaneous absorption

factors to remember

- site of drug action

- pH on top of skin is 4.2 to 5.6

- skin is negatively charged

- need to consider which is rate-limiting step in the process

- need to consider which dosage form to use

steps in process

- dissolution of drug in vehicle

- diffusion of drug through vehicle to skin surface

- route: transepidermal or transappendegeal

- partitioning into SC

- diffusion through protein-lipid matrix of SC

- partitioning into viable epidermis

- diffusion through cellular mass of epidermis

- diffusion through fibrous mass of upper dermis

- capillary uptake and systemic dilution

why can't you take steroids for more than X number of days

- they are lipophilic and accumulate in the area because they are more lipophilic than their environment

biochemistry of drugs and layers of the skin

- a lot of drugs that you take aren't active, and they may get metabolized on surface of skin or in the skin because of enzymes

- adipose tissues serve as a reservoir for lipophilic drugs after diffusion downwards

factors affecting percutaneous absorption: biological

- skin age

- skin condition

- skin site

- skin metabolism

- blood flow

- species

- ex: psoriasis skin is more permeable to drugs

physicochemical properties affecting absorption

- skin-hydration

- drug-skin binding

- vehicle-effects/partitioning

- temperature

- penetration enhancers

- presence of sin conditions

- thermodynamic activity of drug

- time of contact

vehicles

- occlusive to waxy emulsion to powder

- most to least covering

amount delivered depends on

- vehicle and solvents/additives such as permeation enhancers

- using a particular vehicle/penetration enhancer combination

- physicochemical properties of the active drug

what does a formulation depend on

- the drug; important

ointments

- semisolids which have plastic rheological behavior

- ophthalmic ointments applied to eye

- latin term: unguents

- most occlusive to skin

- patient compliance low-greasy feel

ointment bases: classification

- hydrocarbon bases [most occlusive; most greasy]

- absorption bases [2nd most occlusive]

- water-removable bases [3rd-most occlusive]

- water-soluble bases [least occlusive]

occlusive

- how does it keep water from leaving skin

hydrocarbon bases/oleaginous bases class I

- water-free; insoluble in water; not water washable

- maintain high skin hydration

- most occlusive in this group

- Petrolatum USP/Yellow Petrolatum/ Petroleum Jelly/Vaseline

- White Petrolatum

- Yellow Ointment USP/Simple ointment

- mineral oil/liquid petrolatum

Absorption bases types class II

- already have water in it, which comes in a w/o emulsion [hydrophilic petrolatum and anhydrous lanolin]

- can include water into it, which results in a w/o emulsion [lanolin or hydrous wool fat and cold cream]

- not as much occlusion

- not easily washed off the skin

- ability to incorporate aqueous solutions in these bases is important

hydrophilic petrolatum

- ability to absorb water and produce a w/o emulsion

- formula: cholesterol, stearyl alcohol, white was, white petrolatum

- refined version of Aquaphor which can absorb 3X its weight in water

Anhydrous Lanolin

- refined wool fat

- anhydrous wool fat

- may not contain more than 0.25% water

- insoluble in water but mixes with 2X its weight of water

- w/o emulsion

lanolin USP

- hydrous wool fat

- already a w/o emulsion with 25-30% water already in it

- semisolid, fat like substance obtained from sheeps' wool

- allows further incorporation of water or aqueous solutions

cold cream USP

- semisolid white w/o emulsion

- can be used as emollient or as a base

- formula: white wax, mineral oil, Na Borate, purified water

- cetyl esters wax = cetaceum = spermaceti = spermwax

- Na borate + spermaceti forms and EMULSIFIER

water removable bases class III

- water washable bases

- o/w emulsions, which can be washed off more easily

- ability to also absorb serous discharges in certain derm conditions

- resemble creams in appearance

hydrophilic ointment USP

- methyl paraben, propyl paraben, N lauryl sulfate, propylene glycol, stearyl alcohol, white petrolatum, water

- Na lauryl is anionic emulsifier

- incompatible with acids

- can use nonionics

example of non ionics

- Brij series, which is a polyoxyethylene lauryl ether

Water-soluble bases

- greaseless bases

- unlike class III, only contain water soluble components

- soften greatly on addition of water, so it is better to add non-aq solutions or solids

- ex: PEG

PEG Ointment

- vary from soft to very hard waxes

- not occlusive

- may hinder percutaneous absorption and lead to dehydration of the skin

selection of base

- depends on rate of release of drug from base

- does percut, penetration need to be increased by base?

- does skin need to be occluded?

- short/long term stability of drug in base?

- consistency of base required?

preparation of ointments

- incorporation method

- fusion-fatty materials are added in order of increasing melting points

- method depends on ingredients and whether heat can be used

- fusion method involves heat

- can degrade drug components-examine stability

creams

- viscous liquid or semisolid emulsions

- either w/o or o/w

- used as emollients/medicated bases

- easier to spread on skin, so it is preferred over ointments by patients

- no greasy feeling on skin

- easily removed

vanishing creams

- stearic acid creams

- o/w

- large amount of water and stearic acid

- after application, water evaporates leaving this residue film of stearic acid

- very popular cream base

- high patient compliance

cream bases contain either

- long chain alcohols: cetyl C16 or stearyl C18

- long chain esters: myristates C14, palmitates C16, or stearates C18

- Long chain acids: palmitic C16, or stearic C18

Cream Base o/w Vanishing Cream -

2 Phases: __________ & __________ phase.

- oleaginous

- aqueous

pastes

- highly concentrated suspensions

- similar to ointments but stiffer with larger % of solid

- good for acute lesions that are oozing or crusting

- Ex: Zinc oxide paste USP or Lassar's Paste

- triamcinolone acetonide Dental paste USP

antioxidants

- quinoline type: tocopherol

- organic acids: ascorbic, citric acids

general preservatives for topicals

- mercurials: thimerosal

- hydroxybenzoates: methyl, propyl, butyl parabens

- quaternary ammoniums: benzalkonium chloride, cetrimide

products: ointments and creams

- analgensics: capsaicin cream

- antiacne: tretinoin cream/Retin-A

- antianginal: nitroglycerin ointment

- antibacterials: nystatin cream and Neosporin ointment

- antifungals: miconazole nitrate

- antineoplastics: fluorouracil cream

- astringents/protectants: zinc oxide ointment

- depigmenting agents; hydroxycinnamic acids

marketed products: topical gels

- clindamycin

- clobetasol propionate

- metronidazole

- podofilox

- timolol male

- tretinoin