Topical Flashcards

1
Q

Stratum corneum

A
  • main barrier to permeation
  • the dead cells of the bricks are not permeable
  • permeation occurs by going through the lipid material (mortar) between the dead cells (bricks)

Function: lipid protective barrier

STATE OF HYDRATION IS DIRECTLY RELATED TO EASE OF PERMEATION

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2
Q

Living epidermis

A
  • living cells that do not contain capillaries
  • obtain nutrition by diffusion from dermis
  • source of skin color and tanning
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3
Q

Dermis

A
  • contains capillaries
  • DRUGS MUCH REACH THESE CAPILLARIES TO HAVE SYSTEMIC EFFECT
  • contains pain, thermal, and tactile sensors
  • must reach this layer to cause scarring
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4
Q

Hair Follicles & Sweat glands

A
  • secondary form of drug absorption that bypasses the stratum corneum
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5
Q

Functions of Skin

A

Containment
- confine the tissues and restrain the movement

Microbial Barrier
- pH is 5 which inhibits growth of bacteria

Chemical Barrier
- permeability resistance of stratum cornerum

Radiation Barrier
- exposure of UV stimulates melanin synthesis absorbing UV rays

Electrical Barrier
- high impedance to flow of electrical current
- must use salt solutions to overcome impedance

Thermal Barrier
- maintains 98.6 degree F

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6
Q

Topical Drug Delivery

A

local effects on barrier function

  • surface effect
  • stratum corneum effect
  • effects skin’s glands
  • effects on deep tissue
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7
Q

Transdermal Drug Delivery

A
  • systemic effects
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8
Q

Topical Local Effects

A

Surface Effects
- zinc oxide for diaper rash
- sun block/sunscreen
- lip balm
- calamine lotion
- deodorant
- soap

Stratum corneum Effects
- emolliency: softening horny tissue
- keratolysis: chemical digestion and removal of horny tissue

Glands
- Antipersipriants: aluminum chloride
- Acne: soap, alcoholic solution, antibiotics, retinoids
- Hair remover (depilatory)

Deep Tissues
- corticosteroids
- NSAID (diclofenac)
- anesthetic (benzocaine)
- lighten pigmented skin (hydroquinone)
- skin cancer (5-fluorouracil)

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9
Q

Ointments

A

Hydrocarbon Base (most hydrophobic)
- petrolatum
- polyethylene dissolved in mineral oil

Silicone Base (slightly hydrophobic)
- contains polydimethylsiloxane oil

Absorption Base
- ointment containing W/O emulsifiers

Water Soluble Base (most hydrophilic)
- polyethylene glycol ointment

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10
Q

Pastes

A

ointment into which a high concentration of insoluble particulate solid is added

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11
Q

Creams

A

O/W or W/O emulsion

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12
Q

Gels

A

liquid phase trapped in matrix of natural or synthetic polymer (tragacanth, pectin, carrageenan, methylcellulose)

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13
Q

Foams

A

air or gas emulsified liquid phase

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14
Q

What type of drugs are we interested in transdermal delivery?

A
  • short systemic 1/2 life
  • extensive 1st pass metabolism
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15
Q

Advantages of Transdermal

A
  • good compliance
  • constant delivery of drug
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16
Q

Components of Transdermal Patch

A

Backing membrane
Drug Reservoir
Rate Controlling membrane
Skin contact adhesive

17
Q

Requirements for Transdermal Drug

A
  • high skin permeability
  • low dose requirement (high potency)

Desire hydrophobic small drugs

18
Q

Types of Transdermal Patch

A

Membrane Modulated
- backing membrane
- drug reservoir
- rate controlling membrane
- adhesive

Adhesive Dispersion
- backing membrane
- drug reservoir
- rate controlling adhesive

Matrix Dispersion
- backing membrane
- drug + adhesive = matrix

19
Q

Active Ingredients in Patches

A

Clonidine (very small; not very hydrophobic)
estradiol/noregestromin
lidocaine
lidocaine + epinephrine
nicotine (very small; not very hydrophobic)
nitroglycerin (very small; not very hydrophobic)
estradiol (very small and hydrophobic)
oxybutynin
scopolamine
tesosterone
fentanyl (relatively small and hydrophobic)

Commonality: small and/or hydrophobic

20
Q

Example of Membrane Modulated

A

Nitroglycerin (227 Da)
- 1/2 life: 3 min
- slightly water soluble
- Indication: prevent angina due to CAD

21
Q

Example of Adhesive Dispersion

A

Rivastigmine (250 Da)
- sparingly water soluble
- very soluble in ethanol, acetonitrile, n-octanol, ethyl acetate
- LogP: 2.3 (in between)
- Indication: dementia associated with Alzheimer’s Disease/Parkinson’s
- 4.6mg/24h
- 9.5mg/24h
- 13.3/24h

22
Q

Example of Matrix Dispersion

A

Xulane
- 150 mcg/day norelgrstromin + 35 mcg/day EE
- Backing Layer: polymer layer for structure support
- Middle Layer: adhesive + matrix + drug
- Third Layer: release liner
- once a week for 3 weeks on upper arm, abdomen, butt, back

Warning
- smoking can cause CV risk
- risk of VTE
* risk is higher for patch than oral because Css is 65% higher

23
Q

Drug Diffusion in Skin

A
  1. across cellular-intercellular regions
  2. across lipid intercellular spaces
  3. across thin lipid layers sandwiched between flattened protein cells
24
Q

Factors Affecting Permeability

A

Hydration
- more hydrated, great drug permeability
- water with polar head groups of lipid bilayer loosens lipid packing

Solubility

Excipient
- solvent, surfactant

pH
- affects drug ionization status –> desire unionized drug

25
Alternatives to Help With Permability
Iontophoresis - uses low voltage electrical current to drive charged drugs through skin Electroporation - uses high voltage to create transient pores in skin Ultrasound - uses low frequency ultrasonic energy to disrupt stratum corneum Prodrug - makes lipophilic (hydrophobic) Enhancers (most common): alcohol, DMSO, surfactant, acetone, ethyl acetate
26
Ionic Surfactant
disorders lipid layer of stratum corneum to swell or leach out some structural components reducing resistance
27
Ascorbate/Diothiothreitol
reducing agent that disrupts disulfide bonds of proteins in cells
28
Azone
nonpolar, oil liquid that fluidizes intracellular lipid lamella of stratum corneum in the hydrophobic tails
29
DMSO
dipolar solvent that enters the aqueous region of stratum corneum interacting with lipid polar heads to expand hydrophilic region between the heads
30
Microneedles
- make the holes mechanically Type 1: pretreatment to increase permeability before patch is applied Type 2: needles coated with drug and released while embedded into skin
31
Common Errors
Preparation - removal of patch from packaging - removal of protective foil - alternation of patch Removal Application Monitoring heat Storage