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Activity 5 & 6: Factors affecting percutaneous absorption of drugs…
Activity 5 & 6: Factors affecting percutaneous absorption of drugs from topical products
Percutaneous absorption
the transfer of drugs from the skin surface, into the stratum corneum, under the aegis of a concentration gradient and its subsequent through the underlying epidermis, through the dermis and the microcirculation
Human skin
the stratum corneum, being
keratinized tissue
, behaves as a semipermeable membrane, and drug molecules penetrate by passive diffusion
it is the major rate-limiting barier to transdermal drug transport
once through the stratum corneum, drug molecules may through the deeper epidermal tissues and into the dermis
when the drug reaches the vascularized dermal layer, it becomes available for absorption into the general circulation
routes of penetration
hair follicles with their associated sebaceous glands
via sweat ducts
transceullular or interceullar
their fractional area available for absorption is small (about 0.1%) and this route usually does not contribute appreciably to the steady-state flux of a drug. However, the route may be improtant for ions and large polar molecules that cross intact stratum corneum with difficulty.
factors affecting absorption
physicochemical factors
skin hydration
temperature and pH
diffusion and coefficient
drug solubility
drug should have a greater physicochemcial attraction to the skin than to the vehicle so that the drug will the vehicle in facor of the skin
some solubility of the drug in both lipid and water is though to be essential for effective percutaneous absorption
the aqueous solubility of a drug determines the concentration presented to the absorption site, and the partition coefficient influences the rate of transport across the absorption site
paritition coefficient
molecular size and shape
drug concentration
the amount of drug percutaneouls absorbed per unit of surface area per time interval increases with an increase in the concentration of the drug in the TDDS
area and time of appliccation
the longer and larger, the more drug absorbed
biological factors
skin condition
hydrated skin favors percutaneous
the TDDS acts as an occlusive moisture barrier through which sweat cannot pass, increasing skin hydration
intact, healthy skin is a strong barrier
permeability increases: the skin inflamed, with loss of stratum corneum and alterted keratinization
permeability decreases: the organ thickened, with corns, callueses, and warts
skin age
blood flow
regional skin sites
skin metabolism
IVPT
when:
characterizes the rate and extent to which a drug permeates into and through the skin for a product bathc
characterize the influence of prtocess, formulation and/or manufacturing differences on a drug product by comparing the rate and extent to which a drug permeates into and through the skin. this may occur in the context of comparing prototype formulations of a topical product or potentially in the context of comparing postchange (test) and prechange (reference) products
characterize the influence of prtocess, formulation and/or manufacturing differences on a drug product by comparing the rate and extent to which a drug permeates into and through the skin for a prospective generic (test) product and an approved (reference standard) product, which can support a demonstration of bioequivalence in certain situation
parts
receptor chamber
compartment where the drug released from the dosage if collected
must have a stirring mechanism
sampling port
heated in awater abth
donor chamber
where the dosage form is place
must be covered to prevent product contents evaporation
biological membrane
dermatomed human skin sourced from cadaver or elective surgery or dermatomed procine
enhancers
chemical
increases skin permeability by reversibly damaging or altering the physicochemcial nature of the stratum corneum to reduce it diffusion resistance
among alterations are
increased hydration of the stratum corneum and a change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action, or denaturation or both
characterisitics of an "ideal" penetration enhancer
pharmacologically inert, chemically stable
potent at low conc
compatible with all formulation components, excipients and drugs
nontoxic, nonsensitizing, nonirritant
barrier function readuliy restored on removal of the enhancer
unidirectional action (i.e. enhancing drug penetration without causing loss of material from inside the body)
physical