201 skin Flashcards
what drugs can penetrate the skin
-intermediate partition coefficient (not too polar or non-polar)
-if weak acid or weak base, it should be unionized
-low molecular weight (<500)
-log p (1-3.5)
-high potency
- aqueous solubility (>100μg/ml)
-non-irritant to skin
-high permeability coefficient
what are different dosage forms in topical drug delivery
-creams (o/w or w/o)
-ointments (greasy, viscous)
-gels (aqueous)
-pastes (very viscous, contain undissolved solid)
-sprays
-dusting powders
-patches
how can we provide occlusivity
- hydrophobic polymer (plaster, patch)
-ointment (white soft paraffin)
-w/o cream
what is microdialysis
- use it to evaluate topical drug delivery
-involves insertion of a dialysis tubing into skin
-perfusate pump through tubing
-drug molecules enter perfusate
-analyisis
what are other methods of evaluating topical drug delivery
-tape stripping :layers of skin are removes using a tape
drug on tape removed with solvent and quantified
-physiological response: relies upon the drug having some form of physiological effect (vasodilation- laser droppler velocimetry used to monitor blood flow)
-franz-type diffusion cells (in vitro)- different skin membrane option (human, animal, synthetic)- samples removed and quantified (receptor fluid is aqueous and buffered at specific pH, co-solvents used, maintain at constant temperature 37C)
why is the transdermal route desirable
-avoids first pass metabolism
-controlled rate of drug delivery
-avoids GI problems
-can be administered by the patient
-favored by patients
-reduces dosage frequency
what are the challenges of topical drug delivery
-only potent drugs suitable
-drugs metabolized by skin
-unsuitable for irritant drugs
-more expensive to manufacture
-small volume of distribution required/ lag-time
-tolerance induced by plasma levels
how do we calculate the Kp (permeability coefficient)
log Kp= 0.71logP- 0.0061MW- 2.74
J=Kp*C (μg cm s)
how can we increase the number of drugs deliverable transdermaly
-formulation manipulation (switching to occlusive formulation or employing a cosolvent
-skin modification: penetration enhancers (increase rate of dissrupsion of permeant through the skin
disrupt the highly ordered multiple lamellar lipid arrangement
interact with intercellular properties
increase partitioning into the skin
what are the ideal propertied of enhancers
-non-toxic
-no pharmacological activity
-act rapidly reversibly
-compatible with drug and excipients
-cosmetically acceptable to patients
what are the ideal properties of adhesives
-non-irritant
-keep patch in place for the duration of treatment
-compatible with drug and excipients
-allow bathing but also removable
what are the ideal propertied of backing layer
-needs to be strong but permit multidirectional strech
-can be opaque or clear
-may be occlusive for shorter duration use but permeable for longer
-should not interact with drug or other excipients
what are the ideal properties of a liner
-should be easily removed by the patient
-polymeric or aluminum foil
-compatible with formulation
-usually occlusive to prevent loss of volatile adhesive components
what are the types of patches
-drug-in-adhesive patch
-drug-in-matrix patch (controlled release)
-rate-limiting membrane patch
what are the physical enhancement methods
- electrocorporation (high voltage electrical current is applied to skin to create pores
-sonophoresis (skin temperature increases, cavities and bubbles are created at corneocyte-lipid interface and this dirsupts the SC- ultrasound
-micorneedles (create channels through the SC)
-iontophoresis (involves use of low electric current to drive drugs across the SC), can work for neutral drugs by electroosmosis
works best for cationic drugs because skin has negative charge
-reverse iontophoresis: extract drugs/molecules from skin (both charges and uncharged molecules)- glucose monitoring
what are the functions of the skin
-protect against hear, injury, UV and infections
-regulation of body temperature
-retention/excretion of water
-sensory detection
-synthesis of essential molecules
what is the processes of keratinization
-s. basale : mitosis
-S.spinosum: cells become specialised
-s.granulosum: increased keratin and lipid production (organelle breakdown)
-s.lucidum: dead cells containing keratin filaments
-S.corneum: many layers of squamous cells containing keratin (waterproof)
what are the resident and the transient residents of the skin
-Resident: constantly found in microbiota, stable, not associated with infections
-transient: temporary, removed by washes, associated with opportunistic infections
why is skin a barrier for infections
-low pH
-low moisture content
-nutrient poor
-production of a range of antimicrobial molecules (antimicrobial peptides, lysozymes- phagocytose bacteria)
-constant exfoliation of cells
-microbiota residents prevent colonization
eg propionibacterium. acnes : release fatty acid (low pH)
staph.apidermis: inhibit s.aureus, induce keratinocytes to produce antimicrobial peptides
what can cause skin infections
-cuts
-alteration of normal microbiota (metabolic changes, antibiotic)
-co-infections
what are the virulence factors of S.aureus and strept. pyogenes? (both gram+)
-invade tissues (hyaluronidase: breaks down proteogycian)
-evade host defences (produce coagulase, neutralise AMPs)
-cause host damage (exfoliatins-skin separarion, toxic shock syndrome, enterotocins)
can cause impetigo
-strep.pyogenes: invade tissues (hyaluronidase)
evade host defences (M protein- evades phagocytosis)
exotoxins (streptolysis O and S- lyse RBC and neutrophils)
can cause non-bullous impetigo
what is bullous and non-bullous impetigo
what are the complication of impetigo
non-bullous: thin-walled vesicles that rupture quickly, leaking pus and becoming brownish crust
-bullous: larger fluid-filled blisters, their rupture leaves a thin flat yellow crust
-complications: scalded skin syndrome (exotoxins spread)
toxic shock syndrome (fever, hypotension, organ failure)
