Percutaneous delivery of cosmetic actives to the skin Flashcards
Types of transepidermal routes
transcellular
intercellular
essentials for characterization of actives
Molecular weight dissociation constant solubility octanol/water partition coefficient net ionic charge
Penetration ability based on ionic charge
un-ionized penetrates better than ionized
penetration can be enhanced by keeping the pH of the formulation close to
pKa of active
Optimal partition coefficient
intermediate (log P O/W 1-3)
- adequate solubility within lipid domains of SC to permit diffusion
- sufficient hydrophilic nature to allow partitioning into viable tissues of epidermis
What is partition coefficient
ratio of concentrations of an active molecule in oil and water phases in the skin, due to the fact most compounds are soluble to some extent in both organic and aqueous phases.
Formulation strategies to enhance skin penetration
- Increasing drug diffusion in the skin
- increasing drug solubility in the skin
- increasing degree of saturation of drug in formulation
The ability of vehicles to deliver actives is based on
diffusion of actives through various skin compartments (epidermis and dermis)
Partitioning of actives from dosage form is highly dependent on
relative solubility of active in components of delivery system and SC
Sequence of percutaneous absorption
- Partitioning of molecule from applied vehicle phase –> SC
- molecular diffusion through SC
- Partitioning from SC –>viable epidermis
- diffusion through epidermis/upper dermis/capillary uptake
Supersaturation boosts active penetration by
creating diffusional concentration gradient across SC
Eutectic blends increase solubility of a material in skin lipids by
lowering melting point of active to around or below skin temperature
Ultimate goal of penetration enhancement
target active in SC and/or epidermis without allowing for systemic absorption
effect of alcohol on delivery
fluidizes SC
alters permeability of SC
effect of propylene glycol on delivery
alter permeability of SC
alter vehicle SC partition coefficient
Surfactants effect on delivery
reduce emulsion particle size
solubilize active
Types of submicron delivery systems
Liposomes
niosomes
lipid particles
nanocapsules
Liposomes are used for ______ actives, and the phospholipids forming these liposomes has what effect
hydrophilic
enhance penetration of encapsulated active ingredients
composition of liposomes
heterogeneous lipid composition with several coexisting domains exhibiting different fluidity characteristics
Niosomes are used for ________ because _______
active molecules with a wide range of solubilities
they consist of hydrophilic, amphiphilic, and lipophilic moieties
Lipid particles (SLNP) can be used as penetration enhancers through the skin because of this method protects drug against chemical degradation due to
occlusive and hydrating properties
little or no access for water to enter inner area core of lipid particle
Franz cell apparatus measures _______ skin permeation by
in vitro
formulation added to top of cell covered with biologic membrane/skin substitute
periodic samples are taken to develop time-penetration profile
In vivo active penetration can be measured with _______, in which penetration of the active is estimated from _______
tape stripping
amount recovered in SC by adhesive tape stripping
Microdialysis is used for ______ and ________, and is based on _________
in vivo and ex vivo cutaneous delivery of actives
passive diffusion of compounds down concentration gradient across semi-permeable membrane
Real time tracking of drug in skin layers can be obtained through
Confocal Roman Microspectroscopy, which gives information from deep layers under skin surface
