Transdermal Drug Delivery Flashcards
state how to deliver a drug through Transdermal delivery
Iontophoresis
microneedles
explain Transdermal patches
Transdermal patches- medical adhesives placed on the skin to deliver a dose of medication through the skin into the bloodstream
what was the first transdermal delivery
1st Transdermal drug delivery- TransdermalScop (1979) scopolamine based patch for motion sickness, nausea and vomiting
The highest selling transdermal patch is _________________
the nicotine patch
state facts about the skin
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
explain the fact about the skin absorption
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)
advantages of transdermal delivery
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
disadvantages of transdermal delivery
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
what are the routes in transdermal absorption?
Trans cellular route
Intercellular route
Trans follicular route
state facts about Trans cellular route
Water soluble drugs
99% of relative surface are 25 m diffusion path length
Drug Delivery is through the lipid structures of SC + corneocytes
state facts about Intercellular route
Lipid-soluble drugs
0.70% of relative surface are 350 m diffusion path length
Drug diffuses through endogenous lipid within SC
state facts about Trans follicular route
0.10% of relative surface are 200 m diffusion path length
state the Formulation principles
Select a suitable drug
Release the drug
Use thermodynamics
Alcohol can help
Occlusion
describe “Release the drug” as a formulation principle
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
describe “Use thermodynamics” as a formulation principle
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
describe “Alcohol can help
“ as a formulation principle
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.
describe “Occlusion” as a formulation principle
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
what is the take home message from the lecture slide?
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
what are factors for the Fundamentals of skin permeation
penetration partitioning diffusion permeation absorption
state facts about Fundamentals of skin permeation
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
state facts about Fundamentals of skin permeation
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
what are the Two important parameters important for the Fundamentals of skin permeation
lag-time and steady state flux
what is lag time and steady state flux?
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
Maximise ___ and ________( affinity for SC > affinity to the vehicle)
Cv and Kp
In steady state situation:
Jss = ______________ = ___________________
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)
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
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
what are the facts when you Consider the steady state situation in slide 23
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
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
The rate of transfer (the flux) per unit area is proportional to __________________
he concentration gradient across a membrane (i.e. skin)
state transdermal drugs, their molecular weight and indication
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
what are the general formulation options?
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
how do skin types affect choice of formulation?
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
how does Clinical rational mainly dictates choice for topical delivery
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
how do we Seek delivery to the skin
Aqueous or oil-based formulation which may include isopropyl myristate, propylene glycol
Alcohol based formulations may enhance delivery by volatisation and supersaturation
how do we aim to enhance delivery through the skin:
Aqueous or oil based formulation
May include: alcohols, glycols, oleic acid (can be a combination)
Combination of solvents
As above alcohol may enhance delivery
what are the 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
state facts about Enhancement of transdermal drug delivery?
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
state things to know about formulation manipulation?
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
how does Adhesive patch work? give a brand that uses this
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®)
how does Layered patch work? give a brand that uses this
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 ®
how does Reservoir patches work? give a brand that uses this
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®
what are the different Components in a patch?
Release liner Adhesive Backing layer Matrix/reservoir Rate-limiting membrane
state facts about the Release liner as a component in a patch
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
state facts about the Adhesive a component in a patch
Adhesive
Crucial component of all TDDS
Pressure sensitive adhesives usually used, e.g. acrylates, polyisobutylene or polyloxane adhesives
state facts about the Backing layer as a component in a patch
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
state facts about the Matrix/reservoir as a component in a patch
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
state facts about the Rate-limiting membrane as a component in a patch
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
what must an adhesive have?
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
describe Rate control in transdermal delivery (Clonidine)?
picture the graph of it release?
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
describe Rate control in transdermal delivery (oestradiol)?
picture the graph of it release?
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
Transdermal delivery is very much ________________
determined by the area of contact between patch and skin
state facts about Rate control in transdermal delivery
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
what are the advantages of Transdermal drug delivery: opioid therapy
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.
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?
Upon removal slow decrease depending on half-life and if reservoir is built up
describe Fentanyl TDDS (reservoir and matrix)?
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.
how do Penetration enhancers disrupt the highly organised lipid bilayer packing?
Interacting with cellular proteins
Increasing partitioning into the membrane
Or a combination
Penetration enhancers should be what?
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)
what are the mode of action of Chemical permeation enhancers
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
state different Chemical permeation enhancers?
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)
state different Chemical permeation enhancers?
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)
what are the limitations of Chemical permeation enhancers?
Poor efficiency and toxic
_____is the safest and most widely used Chemical permeation enhancers?
Water
describe water as a Chemical permeation enhancer?
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
describe Ethanol and other low MW alcohols as a Chemical permeation enhancer?
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
describe Dimethyl sulfoxide (DMSO) as a Chemical permeation enhancer?
Dimethyl sulfoxide (DMSO): can interact with lipid bilayer head groups and disrupt close packing
describe Fatty acids as a Chemical permeation enhancer?
Fatty acids e.g. oleic acid: insert along the SC lipid chains to disrupt packing
describe Azone as a Chemical permeation enhancer?
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
describe Terpenes as a Chemical permeation enhancer?
Terpenes (fragrance agent) and surfactant
describe Microporation?
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
what are the Mechanical approaches
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
describe Microneedles
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
what was the Case report on slide 49?
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
describe the Other Microporation techniques
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)
state types of microporation Electrical technique
Electroporation
Iontophoresis
state facts about Iontophoresis
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
state a brand that used Iontophoresis?
Glucowatch®
state facts about Glucowatch®
The GlucoWatch Biographer is a glucose-monitoring device The GlucoWatch®
It apply reverse iontophoresis
describe Electroporation
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
Sonophoresis is an____________
Ultrasound based delivery
describe Sonophoresis
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.
state facts about Sonophoresis
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
state facts about Thermal approaches
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
summarize the lecture?
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
