Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHA 333 > transdermal drug delivery > Flashcards

transdermal drug delivery Flashcards

1
Q

define transdermal drug delivery

A

Delivery of a drug across the stratum corneum

and into the systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

define topical delivery

A

Delivery of a drug across the stratum corneum and

into the deeper skin layers for local action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the advantages of transdermal delivery systems?

A 
• Controlled release of drug into 
systemic circulation
• Decrease in dosage frequency
• Avoidance of liver metabolism
• Increased bioavailability, 
administration of a lower dose
• Safer –no G.I. side effects
• Patient compliance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the limitations of transdermal drug delivery?

A 
• Permeability barrier
– Only small, lipophilic molecules 
can permeate through the skin
• Low dose delivery
– Potent molecule
• Inter- and intra-patient 
variability in skin permeability
– Wide therapeutic window
• Skin irritation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 3 tissue layers of the skin?

A

epidermis, dermis, subcutaneous fat tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is the multicomponent organ the skin comprised of?

A

▪ Three tissue layers: epidermis, dermis, subcutaneous fat tissue
▪ Skin appendages: hair follicles, sweat glands
▪ Epidermal enzyme systems: e.g. esterases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the stratum corneum?

A

the main barrier to drug transport across the skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how is drug removed in the skin?

A

• Drug removed from blood supply in dermis
▪ Concentration gradient between drug on skin surface and the dermal
vasculature –sink conditions
▪ Driving force for diffusion across the skin membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how does drug delivery occur in the skin?

A

Multi-step process of alternating partition and diffusion
▪ Dissolved drug molecules diffuse along the vehicle, towards the vehicle/skin interface
▪ Partitioning of drug from vehicle into the SC, diffusion through SC
▪ Partitioning from SC into viable epidermis, diffusion through viable epidermis (aqueous)
▪ Partition from epidermis into dermis, diffusion through dermal tissue
▪ Partition into capillaries and removal by systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the other potential dates of drug delivery in the skin?

A

▪ “Reservoir effect” = drug binds to keratins in SC
▪ Enzymatic metabolism = drug degradation or activation (pro-drug) by skin enzymes in viable epidermis
▪ Partitioning into subcutaneous fatty layers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how does permeation occur through the stratum corneum?

A

“Brick and mortar” structure of stratum corneum
▪ “Bricks”: corneocytes (terminally differentiated keratinocytes)
▪ “Mortar”: intercellular lipid domain (ceramides, fatty acids, cholesterol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the intrercellular pathway of the SC?

A

▪ Diffusion via the intercellular lipid domain
▪ Main pathway for small, uncharged, lipophilic molecules
▪ Pathlength of permeation (~ 500 μm)&raquo_space; thickness of SC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is the intracellular pathway of the SC?

A

▪ Sequential partition and diffusion across the corneocytes

▪ Pathlength of permeation ~ thickness of SC ~ 20 μm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is appendageal transport?

A

▪ Significant in vivo contribution
▪ Important route for large, polar molecules and ions e.g. iontophoresis, and
vesicular structures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how do the pathways of the SC operate?

A

can operate concomitantly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the mathematical description of passive transdermal delivery?

A

▪ Significant in vivo contribution
▪ Important route for large, polar molecules and ions e.g. iontophoresis, and
vesicular structures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what does the diffusion coefficient D measure?

A

measures the diffusion speed of a molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what does the diffusion coefficient depend on?

A

▪ The viscosity of the diffusional pathlength (η)
▪ Size (radius) of diffusing molecule (r)
▪ Temperature of the skin (T)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the ideal therapeutic properties of a drug for passive transdermal delivery?

A
  1. Therapeutic properties
    • Low daily dose (<10 mg/day)
    • Short half-life (t1/2 ≤ 10 hours)
    • Non-irritating or sensitizing to skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the ideal physiochemical properties for transdermal drug delivery?

A

Low molecular weight (< 500 Daltons)
▪ D is inversely proportional to molecular size of drug
• Aqueous solubility
▪ > 1 mg/ml to be removed by blood supply
• Optimal partition coefficient K (log Ko/w = 1 to 3)
▪ Lipid solubility to diffuse across SC
• Low melting point (< 200 °C)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what are methods to increase drug diffusion via the skin?

A

• Alteration of K, D, Cv variables
– Increase Ksc/v of drug
– Increase D of drug across SC
– Increase Cs of drug in the vehicle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how do you make a hydrophilic drug into a lipophilic prodrug?

A

Attach a lipophilic functional group e.g. ester group
– Prodrug has optimal K
– Prodrug is converted to active drug by enzymes in viable
epidermis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is cmax?

A

maximum solubility of drug in vehicle = saturation concentration of drug
in vehicle i.e. dissolved drug molecules are in equilibrium with solid drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the purpose of chemical enhancers?

A

Diffuse into the skin and reversibly alter the properties of the
stratum corneum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what do chemical enhancers do?

A

• Increase D: disrupt the packing of the lipid bilayers
Accumulate within SC lipids
Aqueous channel formation
e.g. oleic acid, surfactants, sulphoxides (DMSO), azone, alcohols
• Increase D: disrupt protein structure
Alter keratin conformation
Proteins embedded in lipid bilayers
e.g. ionic surfactants, sulphoxides (DMSO, DMF, DMA)
• Alter K: change the solvent nature of stratum corneum
Pyrrolidones, propylene glycol, water, ethanol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the ideal properties with chemical enhancers?

A

– Pharmacologically inactive, non toxic/allergenic, compatible with drug
– Immediate & reversible effect
– Unidirectional action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is the problem with chemical enhacners?

A

safety issues

28
Q

what is an eutectic mixture?

A

Mixture of the drug with another component at a certain ratio where they
inhibit crystallisation of each other

29
Q

what properties does an eutectic mixture have?

A

– Stable formulation

– Eutectic system has a lower melting point than either of the two components

30
Q

what is the ideal solution therapy?

A

– “thelower the melting point of the drug the higher its solubility in the stratum corneum
lipids”

31
Q

why us mp suppression, using eutectic mixture at or below 32 degrease desirable?

A

because it results in a liquid eutectic mixture

32
Q

give examples of eutectic mixtures

A

Ibuprofen-thymol,

lidocaine-menthol, testosterone-menthol, lidocaine-prilocaine (EMLA cream)

33
Q

what are liposomes?

A

Definition: Phospholipid vesicles
– Modify lipid component to imitate stratum corneum lipids (e.g.ceramides): “Cerasomes”
– Topical delivery- reservoir formation in stratum corneum
– Not effective for transdermal delivery

34
Q

what are ethosomes?

A

– Liposomes with 30% ethanol

– Enhance transdermal delivery

35
Q

what are transfersomes?

A

– Elastic liposomes: phospholipid + surfactant + ethanol
– Squeeze through pores in stratum corneum
– Hydration gradient –non-occlusive vehicle

36
Q

define transdermal drug delivery patches?

A

Flexible pharmaceutical preparations containing one or more
active substances, intended to be applied on unbroken skin in
order to deliver the active substance(s) to the systemic
circulation after passing through the skin barrier”

37
Q

how long should you apply transdermal patches for?

A

1-7 days, depending on the medication

38
Q

what are the main patch components?

A

backing layer
liner
adhesive

39
Q

what is the backing layer responsible for?

A

•Protects patch components from environment throughout application
–Occlusive (low water vapor transmission)
–Flexibility

40
Q

what is the liner responsible for?

A
  • Polymer material that covers the adhesive
  • Removed to allow patch application on the skin
  • Occlusive, to minimise loss of volatile patch components
41
Q

what is the adhesive responsible for?

A
  • Attaches patch to skin
  • Polymer: acrylic, polyisobutylene (PIB), silicone
  • Visco-elastic material
  • May contain the drug and excipients
42
Q

what are the two optional patch components?

A

membrane

matrix polymer

43
Q

what is the purpose of the membrane?

A

Moderates the rate of drug release from drug reservoir into the adhesive
layer
• Steady-state drug release

44
Q

what is the purpose of the matrix polymer?

A

Layer containing drug dispersed or dissolved in a polymer matrix

45
Q

what does QC testing test for?

A
  • Uniformity of dosage units BP
  • Uniformity of content BP
  • Dissolution BP
  • Adhesive performance
46
Q

what release patters does a resevoir( membrane controlled) system follow?

A

steady state release

47
Q

what factors should be present in the BP dissolution for transdermal patches?

A

– Temperature of dissolution medium: 32 ±0.5C

– pH of dissolution medium ~ 5

48
Q

how do you test adhesive performance?

A
  • Peel test
  • Tack test
  • Rheological criteria for adhesive performance
49
Q

how does active transdermal delivery work?

A

– Increasing the energy of drug molecules - Iontophoresis,
Electroporation, Sonophoresis
– Bypassing or removing skin barrier - Stratum corneum bypass or
removal

50
Q

what is iontophoresis?

A

Movement of molecules across the skin under the influence

of an electric field

51
Q

what would be the ideal properties dor iontophoresis?

A

broad range of drugs, ideally charged mol

52
Q

what voltage is ued in iontophoresis?

A

use low voltage electric current <1V

53
Q

how can drug transport rate be monitored in iontophoresis?

A

by adjusting the

electrical current

54
Q

what are the properties of the drug resevoir in the iontophoretic patch?

A

– Aqueous, biocompatible gel
– pH to optimize iontophoretic delivery and skin tolerance
– +ve drug at anode, -ve drug at cathode

55
Q

what is the purpose of the return resevoir in the iontophoretic patch?

A

Saline and charged molecules to complete circuit

56
Q

what mechanisms does the ionotropic drug transport work by?

A

Electrophoretic mechanism
– Transport of molecules under direct interaction with electric field
– Charged molecules of low MW
• Electro-osmotic mechanism
– Transport of molecules under the influence of the electrically induced
solvent flow
– Solvent flow: Flux of skin cations from anode to cathode
– Uncharged, large molecules e.g. peptides, or +ve drug molecules

57
Q

how does an E-trans fentanyl system work?

A
  • 24-hour system, administration up to 6 times/hour

* Pain relief within a few minutes after pressing button

58
Q

what is electroporation?

A

Formation of transient aqueous pores in the skin by short

electrical pulses of high voltage

59
Q

what volts is used in electroporation?

A

100 -1000 Volts

60
Q

what does electroporation disrupt?

A

Disruption of lipid structure of stratum corneum

61
Q

how long does it take for electroporation effect to be reversed?

A

seconds to hours

62
Q

what is sonophoresis?

A

Low frequency ultrasonic energy (~ 20 kHz)

• Thermal effect by absorption of ultrasound

63
Q

how does microneedles work?

A

Array of m silicon needles or biodegradable needles
• Microneedles do not reach dermis: pain-free drug delivery
• Pre-treatment of skin or drug administration device
• Microneedles can be either drug-coated or drug-loaded

64
Q

how does powderject system work?

A

Supersonic wave of helium gas

• Solid drug particles (20-100 μm) fired into lower skin layers

65
Q

what does the laser alblation do?

A

Partial or complete removal of stratum corneum
• Has been used for cosmetic resurfacing of skin
• Requires specialised practitioner
• Reversible technique- skin regeneration

PHA 333 (42 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions