Transdermal Drug Delivery

Question 1

state how to deliver a drug through Transdermal delivery

Answer 1

Iontophoresis

microneedles

Question 2

explain Transdermal patches

Answer 2

Transdermal patches- medical adhesives placed on the skin to deliver a dose of medication through the skin into the bloodstream

Question 3

what was the first transdermal delivery

Answer 3

1st Transdermal drug delivery- TransdermalScop (1979) scopolamine based patch for motion sickness, nausea and vomiting

Question 4

The highest selling transdermal patch is _________________

Answer 4

the nicotine patch

Question 5

state facts about the skin

Answer 5

Skin is the largest human organ and serves primarily as a protective coating

Barrier to microorganisms
Barrier to abrasion and physical damage
Protection from UV radiation 
Prevents excessive water loose/gain
Provides mean of regulating body temperature 
Transduces sensory information

Question 6

explain the fact about the skin absorption

Answer 6

Despite the relative importance of the protective function of the skin, it largely resides in the outermost layer, known as stratum corneum

Skin is permeable to lipid-soluble low molecular weight drugs

Epidermis, dermis and hypodermis (subcutaneous tissue)

Question 7

advantages of transdermal delivery

Answer 7

Avoids hepatic first pass metabolism – !Skin Metabolism!
Avoids pain associated with injections
Continuous “Sustained Release” drug delivery with infrequent dosing
Permits self-administration – Vaccines
Non-invasive (no needles or injections) – Needle injuries /contamination
Improves patient compliance
Reduces side effects
Allows removal of drug source
Patient preferred

Question 8

disadvantages of transdermal delivery

Answer 8

Potent drugs only (few mg/24 hours)
Lag Time (not good for acute conditions)
Development of tolerance
Poor diffusion of large molecules
Allergic and Irritant reactions

Question 9

what are the routes in transdermal absorption?

Answer 9

Trans cellular route
Intercellular route
Trans follicular route

Question 10

state facts about Trans cellular route

Answer 10

Water soluble drugs
99% of relative surface are 25 m diffusion path length
Drug Delivery is through the lipid structures of SC + corneocytes

Question 11

state facts about Intercellular route

Answer 11

Lipid-soluble drugs
0.70% of relative surface are 350 m diffusion path length
Drug diffuses through endogenous lipid within SC

Question 12

state facts about Trans follicular route

Answer 12

0.10% of relative surface are 200 m diffusion path length

Question 13

state the Formulation principles

Answer 13

Select a suitable drug

Release the drug

Use thermodynamics

Alcohol can help

Occlusion

Question 14

describe “Release the drug” as a formulation principle

Answer 14

Appropriate release e.g. rapid release or sustained over 7 days
If lipophilic drug in lipophilic base then drug will stay in formulation, aqueous base more suitable
Vehicle should not retain drug

Question 15

describe “Use thermodynamics” as a formulation principle

Answer 15

Use concentration gradient in favour by using drug at near saturated solution levels (solid or saturated solutions has maximum thermodynamic activity)
- Drive to escape vehicle is high

If drugs is added to finely divided suspension formulation with saturated drug, drug concentration increases, but no ‘effective concentration’ which is soluble drug therefore flux is the same

If this suspension becomes diluted then particles dissolve and saturation is still maintained until drug reduces below saturation

Question 16

describe “Alcohol can help

“ as a formulation principle

Answer 16

Many formulations contain low MW alcohols or other volatile ingredients

Alcohols partition into skin and provide a transient reservoir into which drug can partition

May improve the diffusion coefficient of drug into stratum corneum

Good solvent but evaporates from skin

Ibuprofen hydro-alcoholic gels: ibuprofen has low solubility (1mg/ml) in water, but 10mg/ml can be dissolved in 20:80 w/w ethanol:water. Gel of 5mg/ml rubbed into skin will loose ethanol by evaporation, formulation becomes more aqueous and saturated. Maximum thermodynamic activity and therefore transport into skin.

Question 17

describe “Occlusion” as a formulation principle

Answer 17

Covering skin with impermeable membrane

Hydrates skin by blocking trans epidermal water loss (TEWL) to environment

Water content of SC can rise to 400 % dry weight which improves transdermal and topical delivery

Some preparations require it (EMLA – lidocaine and prilocaine)

Some inadvertent – hydrocortisone ointment to treat nappy rash under tight fitting waterproof nappy

Only under care of GP etc. Very short term treatment if no other barrier cream helps.
Growth inhibition and thins the skin

Question 18

what is the take home message from the lecture slide?

Answer 18

Low Molecular weight
Less than 500 Daltons

Lipophilic character (log Poctanol/water)
Drug possessing both water and lipid solubility are favourably
absorbed through the skin
Log P=1-4 generally required for optimal transdermal permeability

Sufficient solubility in water at pH 6-7.4
more than 1mg/mL if targeted drug delivery rate is in the mg/day range

Low dosage administration

Question 19

what are factors for the Fundamentals of skin permeation

Answer 19

penetration 
partitioning 
diffusion
permeation
absorption

Question 20

state facts about Fundamentals of skin permeation

Answer 20

The movement of matter from one region to another following random molecular motion

The rate of transfer (the flux) per unit area is proportional to the concentration gradient across a membrane (i.e. skin)

In the direction of diffusion (from most concentrated to least concentrated regions)

Defined by Fick’s First Law of Diffusion

Sink conditions

Fick’s second law of diffusion states that the rate of change of concentration with time at a point with in diffusional field is proportional to rate of change in the concentration gradient at that point

Question 21

state facts about Fundamentals of skin permeation

Answer 21

The movement of matter from one region to another following random molecular motion

The rate of transfer (the flux) per unit area is proportional to the concentration gradient across a membrane (i.e. skin)

In the direction of diffusion (from most concentrated to least concentrated regions)

Defined by Fick’s First Law of Diffusion

Sink conditions

Fick’s second law of diffusion states that the rate of change of concentration with time at a point with in diffusional field is proportional to rate of change in the concentration gradient at that point

Question 22

what are the Two important parameters important for the Fundamentals of skin permeation

Answer 22

lag-time and steady state flux

Question 23

what is lag time and steady state flux?

Answer 23

Lag-time: effects the time period that is required to reach therapeutic level
LT=h^2/ 6D

Steady state flux: determines whether therapeutic levels can be reached

Question 24

Maximise ___ and ________( affinity for SC > affinity to the vehicle)

Answer 24

Cv and Kp

Question 25

In steady state situation: | Jss = ______________ = ___________________

Answer 25

Jss = {DP/h} Cv = Kp Cv Jss= flux of drug (g/m2) D = drug’s apparent diffusivity in the stratum corneum (m2/s) P= the stratum corneum-formulation partition coefficient h= thickness of the barrier Cv = Concentration in vehicle (donor solution) kp= drug’s permeability coefficient across the skin (formulation dependent) (Assuming that Cv (formulation concentration) is constant and on the other side of the membrane “sink conditions” prevail or the local concentration Cd is much less compared to Cv)

Question 26

in The steady state concentration profile (Fick’s Law), when we assume that : the drug concentration in the topical (Cv – C vehicle) is constant on the other side of the membrane “sink conditions” prevail DUE TO THE EFFICIENT UPTAKE OF DRUG BY THE DERMAL MICROCIRCULATION what happens

Answer 26

Thus Cd (local concentration) is much less than the Cv and Cv-Cd ~ Cv At steady state, the concentration gradient across the membrane is linear , and thus Ficks Law 1st of diffusion applies Fick's first law relates the diffusive flux to the concentration under the assumption of steady state. It postulates that the flux goes from regions of high concentration to regions of low concentration, with a magnitude that is proportional to the concentration gradient (spatial derivative). In one (spatial) dimension And Thus the Flux J is calculated

Question 27

what are the facts when you Consider the steady state situation in slide 23

Answer 27

The drug concentration in the topical (Cv – C vehicle) is constant On the other side of the membrane “sink conditions” prevail ``` DUE TO THE EFFICIENT UPTAKE OF DRUG BY THE DERMAL MICROCIRCULATION Thus Cd (local concentration) is much less than the Cv and Cv-Cd ~ Cv ``` At steady state, the concentration gradient across the membrane is linear , and thus Fick's Law 1st of diffusion applies

Question 28

Fick's first law relates ____________________

Answer 28

the diffusive flux to the concentration under the assumption of steady state. It postulates that the flux goes from regions of high concentration to regions of low concentration, with a magnitude that is proportional to the concentration gradient (spatial derivative). In one (spatial) dimension And Thus the Flux J is calculated

Question 29

The rate of transfer (the flux) per unit area is proportional to __________________

Answer 29

he concentration gradient across a membrane (i.e. skin)

Question 30

state transdermal drugs, their molecular weight and indication

Answer 30

``` Buprenorphine = chronic pain Capsaicin = neutropathy pain ``` Clonidine = hypertention Diclofenac epolamine = Acute pain Estradiol= Menopausal symptoms Estradiol/levonorgestrel =Menopausal symptoms Estradiol/norethidrone = Menopausal symptoms Ethinyl = Contraception Fentanyl = Chronic pain Granisetron = Chemo-induced emesis Influenza-virus vaccine = Influence virus lidocaine with tetracaine = Local dermal analgesia Methylphenidate = Hyperactivity disorder Nicotine = Smoking cessation Nitroglycerin = Angina pectorls Oxybutynin = Overactive bladder Rlvastigmine = Dementia

Question 31

what are the general formulation options?

Answer 31

General: semi-solid formulation for increased residence time transdermal patches for extended drug delivery through the skin liquid formulation for rapid short term input of permeant into skin

Question 32

how do skin types affect choice of formulation?

Answer 32

Skin type may affect choice of formulation: Normal to oily: often gels Normal to dry: often lotions Dry skin: creams Skin site: hairy areas often lotions, gels and sprays and where skin touches or rubs creams or lotions

Question 33

how does Clinical rational mainly dictates choice for topical delivery

Answer 33

Wet, vesicular or weeping lesion - ‘wet’ usually aqueous based formulation (cream, lotion, gel) - Hydrophilic drug: Aqueous based system including water May contain co-solvents e.g. propylene glycol Avoid alcohol -Hydrophobic drug: Mineral oils or aqueous with co-solvent e.g. water with propylene glycol but avoid alcohol Dry, thickened scaly lesion – ‘dry’ usually fatty formulation (ointments and pastes) -Oils and waxes which may include surfactants, glycols depending on formulation and drug solubility

Question 34

how do we Seek delivery to the skin

Answer 34

Aqueous or oil-based formulation which may include isopropyl myristate, propylene glycol Alcohol based formulations may enhance delivery by volatisation and supersaturation

Question 35

how do we aim to enhance delivery through the skin:

Answer 35

Aqueous or oil based formulation May include: alcohols, glycols, oleic acid (can be a combination) Combination of solvents As above alcohol may enhance delivery

Question 36

what are the Various approaches try to increase flux by manipulating

Answer 36

the skin’s barrier properties (increasing diffusivity) nature of the permeant (increasing partitioning) Or to increase the concentration of the drug in the vehicle/formulation (thermodynamic activity) Manipulating skin thickness is difficult but thin skin can be selected

Question 37

state facts about Enhancement of transdermal drug delivery?

Answer 37

Various approaches try to increase flux by manipulating: the skin’s barrier properties (increasing diffusivity) nature of the permeant (increasing partitioning) Or to increase the concentration of the drug in the vehicle/formulation (thermodynamic activity) Manipulating skin thickness is difficult but thin skin can be selected proven by J = { DP / h} Cv

Question 38

state things to know about formulation manipulation?

Answer 38

Maximum flux achieved at saturation Supersaturated solution is where drug is present in excess of solubility E.g. hydro-alcoholic gel containing -Alcohol (good solvent) evaporates and drug exceeds - its solubility in water and becomes supersaturated -Unstable and crystallisation can occur -If formulation is viscous or anti-nucleating polymer is included this can be inhibited for a time -Many of these formulations are dynamic including patches and volatile ingredients can partition into skin or evaporate resulting in transient supersaturates states. -Can also be achieved with a combinations of solvents one poor and one good. If good solvent is removed or balance disturbed the supersaturated solution is created in poor solvent. Partitioning can be encouraged into the SC by using a vehicle in which drug is only moderately soluble Active should have appropriate physicochemical properties e.g. using a pro-drug containing lipohilic moiety Enhances partitioning in lipophilic SC Ester-linked fatty acids can help and link can be cleaved in skin by esterases liberating the active. Control over pH can ensure that neutral compounds are maintained that permeate better Ion-pairing agents can also assist

Question 39

how does Adhesive patch work? give a brand that uses this

Answer 39

simple concept, one layer of drug containing adhesive polymer serves as reservoir with high loading capacity But can constrain period of delivery (nicotine patch for 1 day) the degree of control is small and the ultimate control barrier is the stratum corneum e.g. (Nitro-Dur®)

Question 40

how does Layered patch work? give a brand that uses this

Answer 40

Use different polymer compositions or different polymers to provide drug-containing matrix It might consist from one or more sub-layers Can increase the drug content in system or control drug release allowing longer term delivery The main drawback is the area of contact between the patch and the skin is significantly greater than the “active” area e.g. Deponit ®

Question 41

how does Reservoir patches work? give a brand that uses this

Answer 41

Pioneered from Alza The concept: -a reservoir of the drug (in liquid state) and a polymeric membrane separating the reservoir from the adhesive tape -the membrane acts a rate-controlled element for the drug and is frequently referred to as “rate-controlling membrane Patch should have a reasonable size Area not large enough if high concentration of drug needed to maintain steady state (input depends on clearance and concentration at steady state) e.g. Transiderm-Nitro® and Durogesic®

Question 42

what are the different Components in a patch?

Answer 42

``` Release liner Adhesive Backing layer Matrix/reservoir Rate-limiting membrane ```

Question 43

state facts about the Release liner as a component in a patch

Answer 43

Temporarily covers adhesive layer and when removed allows adhesion to skin Made from polymers e.g. ethylene vinyl acetate or aluminium foil depending on adhesive it covers Must easily peel away but must be bonded firmly to prevent accidental removal Usually occlusive to prevent loss of volatile components e.g. ethanol

Question 44

state facts about the Adhesive a component in a patch

Answer 44

Adhesive Crucial component of all TDDS Pressure sensitive adhesives usually used, e.g. acrylates, polyisobutylene or polyloxane adhesives

Question 45

state facts about the Backing layer as a component in a patch

Answer 45

Backing layer Numerous materials depending on design, size and length of use Relatively short use small patches, occlusive backing layer Will hydrate skin and improve drug absorption, e.g. polyethylene or polyester films Larger longer use patches, some vapour transmission is preferred e.g., polyvinylchloride films Backing layer should allow multidirectional stretch and should be pliable to move with the skin

Question 46

state facts about the Matrix/reservoir as a component in a patch

Answer 46

Usually prepared by dissolving drug and polymers in common solvent before adding excipients e.g. plasticizer Viscosity can be modified by concentration of polymer or by cross-linking chains in matrix and can be used to control diffusion through matrix to adhesive layer and ultimately skin Reservoirs rather have viscous liquids, e.g. silicone or a co-solvent system, occasionally with ethanol In this case drug diffusion is unhindered

Question 47

state facts about the Rate-limiting membrane as a component in a patch

Answer 47

Rate-limiting membrane Transdermal patches were originally designed to control rate of delivery of active ingredient (flux) In reality it is more the stratum corneum that controls the rate Semi-permeable membranes can separate reservoirs from underlying adhesive or multiple drug-in adhesive- layers E.g. co-polymers of ethyl acetate with vinyl acetate, with or without plasticizers Membrane must be compatible with the drug, non-toxic, stable and pliable

Question 48

what must an adhesive have?

Answer 48

Stick to the skin for the patch lifetime Must be non-irritating and non-allergenic (may be in place for up to 7 days) Compatible with drug and other excipients Should allow painless removal without leaving residue on the skin surface Be aware that presence of drug can affect properties and this is only seen in in vivo situ

Question 49

describe Rate control in transdermal delivery (Clonidine)? picture the graph of it release?

Answer 49

Potent antihypertensive Well absorbed in the GI tract (95 %), long half life (6-20h) and modest clearance(13 L/h) Transdermal patch to reduce side effects and patient compliance Reservoir type Patches (3.5 7.0 and 10.5 cm2) allowed dose titration No peaks and valleys” as with b.d. oral administration Induces immunological skin reaction

Question 50

describe Rate control in transdermal delivery (oestradiol)? picture the graph of it release?

Answer 50

Potent drug, high clearance (600-800 L/hr) and short half-life (1hr) High hepatic first-pass effect results to an unfavourable ratio of estrone to the drug itself Sustained plasma concentrations with transdermal application First patch a reservoir worn for 3 up to 4 days (new generation monolithic) Pharmacologically beneficial effects on frequency of hot flushes, sleep disturbance, irritability and mental acuity

Question 51

Transdermal delivery is very much ________________

Answer 51

determined by the area of contact between patch and skin

Question 52

state facts about Rate control in transdermal delivery

Answer 52

Transdermal delivery can be achieved by adjusting the size of the system rather by altering the formulation The delivery is not so sensitive to the loading of the patch especially when the input rate is controlled by the skin (enough loading to ensure that delivery is maintained for certain period, diffusional driving force) The design of a patch does not guarantee that it will control the delivery rate

Question 53

what are the advantages of Transdermal drug delivery: opioid therapy

Answer 53

Advantages: Peaks and troughs avoided of intermittent dosage regimens that can lead to side-effects such as sedation, nausea and vomiting, and respiratory depression The reduced need for dosage administration (72 hourly or weekly) also improves patient compliance. Fentanyl and buprenorphine patches are used in the treatment of cancer and chronic pain. Patch pharmacokinetics render them unsuitable for the treatment of acute pain.

Question 54

referencing slide 46 Comparison of plasma concentrations of buprenorphine after single application of 35 µg h−1 patch (removed after 72 h) and sublingual dosing of 400 µg buprenorphine, eight hourly: After steady state is achieved drug concentrations constant. what happens?

Answer 54

Upon removal slow decrease depending on half-life and if reservoir is built up

Question 55

describe Fentanyl TDDS (reservoir and matrix)?

Answer 55

Fentanyl: Soluble in both fat and water, with a low molecular weight and high potency, it is ideal for transdermal delivery. Fentanyl patches are designed to deliver fentanyl at four constant rates: 25, 50, 75, and 100 µg h−1 for a period of 72 h. After initial application, a depot of fentanyl forms in the upper skin layers and serum fentanyl concentrations increase gradually, generally levelling off between 12 and 24 h. The steady-state serum concentration is reached after 24 h and maintained as long as the patch is renewed. The Durogesic® reservoir patch is mostly phased out and replaced with Durogesic® Dtrans®—a matrix design. In addition to decreasing the risk of accidental overdose with membrane damage, the new matrix system is smaller and thinner than the reservoir.

Question 56

how do Penetration enhancers disrupt the highly organised lipid bilayer packing?

Answer 56

Interacting with cellular proteins Increasing partitioning into the membrane Or a combination

Question 57

Penetration enhancers should be what?

Answer 57

Pharmacologically inert Modify skin barrier in a reversible manner Non-toxic Non- irritating Compatible with drugs and excipients Acceptable to patients (good skin feel, odourless, colourless etc)

Question 58

what are the mode of action of Chemical permeation enhancers

Answer 58

Increasing the fluidity of the SC lipid bilayer Interaction with intercellular proteins Disruption or extraction of intercellular lipids Increasing the drug thermodynamic activity Increasing the SC hydration

Question 59

state different Chemical permeation enhancers?

Answer 59

Solvents alkyl-esters, dimethyl sulfoxide, pyrrolidine Surfactants- sodium lauryl sulfate, SDS Fatty acids-oleic acid, undecanoic acid, linoleic acid Alcohols-octanol, nonanol Terpenes-menthol, limonene, thymol Lactam-laurocapram (Azone)

Question 60

state different Chemical permeation enhancers?

Answer 60

Solvents alkyl-esters, dimethyl sulfoxide, pyrrolidine Surfactants- sodium lauryl sulfate, SDS Fatty acids-oleic acid, undecanoic acid, linoleic acid Alcohols-octanol, nonanol Terpenes-menthol, limonene, thymol Lactam-laurocapram (Azone)

Question 61

what are the limitations of Chemical permeation enhancers?

Answer 61

Poor efficiency and toxic

Question 62

_____is the safest and most widely used Chemical permeation enhancers?

Answer 62

Water

Question 63

describe water as a Chemical permeation enhancer?

Answer 63

Water: safest and most widely used Transdermal flux in most through hydrated skin compared to dry tissue Occlusion is an effective means to increase permeability

Question 64

describe Ethanol and other low MW alcohols as a Chemical permeation enhancer?

Answer 64

Ethanol and other low MW alcohols: Ethanol can disrupt the intercellular lipid packing and increase diffusivity but can also diffuse into membrane act as solvent within SC into which drugs can easily partition

Question 65

describe Dimethyl sulfoxide (DMSO) as a Chemical permeation enhancer?

Answer 65

Dimethyl sulfoxide (DMSO): can interact with lipid bilayer head groups and disrupt close packing

Question 66

describe Fatty acids as a Chemical permeation enhancer?

Answer 66

Fatty acids e.g. oleic acid: insert along the SC lipid chains to disrupt packing

Question 67

describe Azone as a Chemical permeation enhancer?

Answer 67

Azone: posesses and bulky polar head group and lipid chain | Can insert with in the lipid lamellae and disrupt at both head groups and chains

Question 68

describe Terpenes as a Chemical permeation enhancer?

Answer 68

Terpenes (fragrance agent) and surfactant

Question 69

describe Microporation?

Answer 69

Most effective strategy to overcome the skin’s barrier properties is based on the formation of micropores into the stratum corneum ``` Microchannels can be formed by external means such as Microneedles Ultrasound Electroporation Radiofrequency Lasers ``` The further success of transdermal drug delivery of large pharmaceuticals drugs is believed to be the understanding and maintenance of skin pores

Question 70

what are the Mechanical approaches

Answer 70

Tape stripping: Simple method to remove the stratum corneum using a single adhesive tape Microneedles (MN) arrays: First envisioned in 1971- patented in 1976 Multiple microscopy projections assembled on one side of patch Length: 25-200 um Based width: 50-250 um Tip diameter: 1-25 um

Question 71

describe Microneedles

Answer 71

Offer painless and powerful dermal permeabilization Long enough to perforate the topmost layer of epidermis but too short to excite nerve ending in the skin Skin recovers its barrier function within 3-4 hr and microchannels are closed within 15 hr of poration

Question 72

what was the Case report on slide 49?

Answer 72

Naltrexone, hydrophilic molecule that when administered orally undergoes significant first-pass metabolism with a highly variable 5–40% systemic bioavailability but the microneedle patch improved bioavailability and the Plasma levels of NTX are 2–4 ng/ml, ACHIEVED

Question 73

describe the Other Microporation techniques

Answer 73

Various energy forms are applied to the skin to induce cavitation pores or channels. These approaches are particularly adapted for the delivery of hydrophilic macromolecules, pores closed after 48-72hr Examples: human growth hormones (radiofrequency), gene transfer (laser), insulins (sonoporation, electroporation, laser), vaccine (sonoporation, electroporation). Depending on the energy used, one can use electrically facilitated approaches such as Iontophoresis (application of electrical currents) Electroporation (high voltage pulse) As well as : Sonoporation (low frequency ultrasound cavitation) Thermal ablation (Heating sources such as laser, radiofrequency)

Question 74

state types of microporation Electrical technique

Answer 74

Electroporation | Iontophoresis

Question 75

state facts about Iontophoresis

Answer 75

Skin patches use physically acceptable electrical currents between 0.1-1 mA centimetre squared, applied for minutes to hours from an externally placed electrode in order to drive the drug across the stratum corneum. This approach has shown success for drugs that can be benefiting from the use of an electric current to increase the speed or rate of delivery, such as lidocaine, fentanyl, or most lately, a drug against migraines, Sumatriptan, known under the commercial name of Zecuity The transdermal transport rate is proportional to the applied constant current, an enabling enhancement of transdermal dose and control of drug delivery kinetics The amount of drug delivered is determined by the maximal current applied before the pain level is reached. This approach is not adapted to the delivery of large molecules

Question 76

state a brand that used Iontophoresis?

Answer 76

Glucowatch®

Question 77

state facts about Glucowatch®

Answer 77

The GlucoWatch Biographer is a glucose-monitoring device The GlucoWatch® It apply reverse iontophoresis

Question 78

describe Electroporation

Answer 78

Pores are formed through the application of short and high voltages, 50-500 volts Properly designed systems can minimize the sensation from the voltage pulses and facilitate drug delivery, especially of hydrophilic and charged molecules into the skin Small and higher molecular weight drugs can be delivered into the skin Main drawbacks are the lack of quantitative delivery, cell death with damage of proteins and, thus, the bioactivity This approach is only at the research states, with regards to transdermal delivery

Question 79

Sonophoresis is an____________

Answer 79

Ultrasound based delivery

Question 80

describe Sonophoresis

Answer 80

The concept of ultrasound for transdermal drug delivery was initially reported in 1950, with the first transdermal application approved in 2004 for the delivery of a local anesthetic. Ultrasound is an oscillation sound pressure wave and can be used to transport drugs across the skin. Frequencies of 20 kilohertz to 60 megahertz have a sufficient intensity to reduce the resistance of the skin.

Question 81

state facts about Sonophoresis

Answer 81

Delivery of drugs independently of charge and size. The proposed mechanisms by which ultrasound affects tissue and cells include thermal effects, as well as cavitation effects This concept has been approved as a pre-treatment prior to the application of lidocaine as a means of accelerating local anesthesia. High-intensity ultrasounds can cause second-degree burns, limiting the delivery of many macromolecules

Question 82

state facts about Thermal approaches

Answer 82

Thermal ablation approaches are methods based on drug deliveries through the skin by heating the surface of the skin The stratum corneum is selectively depleted at the site of heating without deeper tissue damage Many methods can be used to cause thermal ablation, such as lasers, radiofrequency, and electrical heating elements To avoid damaging the underlying epidermis, the thermal exposure should be short, so that the temperature gradient across this stratum corneum can be high enough to keep the skin surface hot, but that the temperature of the viable epidermis does not experience a significant temperature rise When the skin is exposed to a temperature above the physiological temperature over an extended period of time, skin tissue damage can occur Here you can see the histological analysis of skin using conventional staining, heating for 10 minutes at 52 and 60 degrees At 52 degrees, normal dermis characteristics are seen. The epidermis, as well as the dermis, are unharmed. At 60 degrees, however, one sees tissue necrosis

Question 83

summarize the lecture?

Answer 83

Transdermal drug delivery technologies are one of the fastest growing sectors within the pharmaceutical industry Advances in drug delivery systems are having increases in prolonged rate-controlled delivery with several side effects as well as increased efficiency and constant drug delivery The development of physical enhancement methods allows for the delivery of micropolar drugs. The future of transdermal drug delivery might, therefore, be bright