Transcript Advantages - pharmacist

Definition:
Transdermal drug delivery system can deliver the
drugs through the skin portal to systemic circulation
at a predetermined rate and maintain clinically the
effective concentrations over a prolonged period of
time.
• Reasonably constant dosage can be maintained.
• First pass metabolism in the liver and GI tract is avoided
• Reduced need for drug readministration (some patches can
last 7 days)
• Easy to apply, to remove, and to monitor
• Allows effective use of drugs with short biological half-life.
• Allow administration of drugs with narrow therapeutic
window because drug levels are maintained within the
therapeutic window for prolonged periods of time.
• Reduced inter and intra patient variability.
• Drugs
that
administered
require
high
blood
levels
cannot
be
limited only to potent molecules, those
requiring a daily dose of 10mg or less.
• Transdermal administration is not a means to achieve
rapid bolus type drug input.
• Adequate solubility of the drug in both lipophilic and
aqueous environments, to reach dermal microcirculation
and gain access to the systemic circulation.
• The molecular size of the drug should be reasonable to be
absorbed percutaneously.
The drug must traverse three layers, the stratum cornium,
the epidermis, and the dermis.
Of these, the toughest barrier is the stratum corneum,
which consists of 10-25 layers of keratinized cells.
• Hydrophilic drugs permeates by Intercellular pathway drug
molecule passes through the cells of the stratum corneum, As
stratum corneum hydrates, water accumulates near the outer
surface of the protein filaments
• Lipophilic drugs permeates by Transcellular mechanism.
These molecules dissolve in and diffuse through the nonaqueous lipid matrix imbibed between the protein filaments
• Penetration enhancement is the most critical factor in
transdermal systems, so as to improve flux.
• Flux (J) can be defined as the amount (M) of material flowing
through unit cross section (S) of a barrier in unit time (t).
• Flux can be given by: J=dM/S.dt.
• Each phase of the membrane have a diffusional resistance(R),
which usually is the function of :
• thickness (hs) of the phase
• the permeant diffusion coefficient (Ds) within the phase
• the partition coefficient (Ks) between the membrane phase
and external phase.
• It can be expressed as: R=hs/Ds.Ks
• P=Ds.Ks/hs
• where P is permeability coefficient.
• The permeability coefficient is related to membrane flux
(J) as given
J=APs (Cp-Cr)
• where:
• Cp-Cr is the difference in permeant concentration across
the membrane
• A is the area of application.
• Ps is permeability coefficient
1- Prodrugs interactions
• The
prodrug enhance
transdermal
delivery
of
drugs
with
unfavourable partition coefficients.
• involves addition of a pro-moiety (ester moiety) to increase
partition coefficient and solubility to increase the transport of the
drug in the stratum corneum.
•
Upon reaching the viable epidermis, esterases enzyme release the
active drug by hydrolysis thereby optimizing concentration in the
epidermis
2.Ion-pairs
Charged drug molecules do not readily partition into or
permeate through human skin.
Formation of lipophilic ionpairs increase stratum corneum
penetration of charged species.
This strategy involves adding an oppositely charged species
To the charged drug, forming an ion-pair in which the
Charges are neutralized so that the complex can partition into
And permeate through the stratum corneum. The ion-pair
Then dissociates in the aqueous viable epidermis releasing
The parent charged drug that can diffuse within the
Epidermal and dermal tissues.
3-Chemical permeation enhancers :
• Chemical permeation enhancers A substance that will
increase the permeability of the epithelial barrier by
modifying its structure also termed as accelerants or
absorption promoters-can enhance drug flux.
• Ideal Penetration Enhancer Non-toxic, non-irritating, nonallergenic. Immediate onset of increased permeability.
Immediate recovery of normal barrier properties upon
removal (reversible). Physically and Chemically compatible
with a wide range of drugs
• permeation enhancers include the following :
1. Sulphoxides
3. Polyols
5. Fatty acids
7. Amines and amides
9. Surface active agents
2. Alcohols
4. Alkanes
6. Esters
8. Terpenes
Basic components of TDDS :
• Drug
•
Polymer matrix
•
Penetration enhancers
• Rate controlling membrane
• Adhesive : Serves to bind the components of the patch to the
skin e.g : Acrylic copolymers, polyisobutylene and polysiloxane.
• Release liner: Protects the drug during storage and is removed
prior to use
• Backing membrane :Protects the patch from the outer
environment.
include water impermeable polymer e.g.: Poly urethane films,
Ethyl vinyl acetate, Poly olefins.
•
•
•
•
Transdermal patches
Iontophoresis
Microneedles
High velocity jet injectors
Transdermal patches
•
•
•
•
Advantages of skin patch:
Easy to apply and to remove.
Avoids liver (“first pass” effect)
Improves patient compliance
•
•
•
•
Disadvantages of skin patch:
Can irritate skin
Adhesive bond may fail
Sometimes slow to take an effect
• Transdermal matrix system :
• Rate controlling factors include:
• Drug concentration in polymer matrix
• Chemical nature of polymer matrix
• Geometry of device
Polymers: PVP, Ethylene vinylacetate, polypropylene.
Initially the drug is released rapidly, then rate declines as matrix
Is depleted.
Advantages:
• Sleeker and thinner
• daily or multiple-day Applications.
• Appropriate for drugs that penetrate readily and/or have low
dosage requirements.
Schematic Drawing of the Matrix patch.
Film Backing
Drug suspension/semisolid
matrix
Adhesive Layer
Protective Liner (removed prior to use)
skin
• Transdermal reservoir system :
• Rate controlling factors include:
• Membrane thickness
• Membrane permeability
Polymers: Cellulosic esters, polyamides or PVC.
Advantages:
• Used when matrix systems cannot penetrate skin
• Used when drugs require significant penetration
enhancement and/or high dosage levels.
Reservoir Patches
• The reservoir system has a drug layer that is
separate from the adhesive.
Schematic Drawing of the Reservoir type of patch.
Film Backing
Drug Layer
Rate-controlling Membrane
Contact Adhesive
Protective Liner (removed prior to use)
skin
• Drug-in-Adhesive
• Single-layer Drug-in-Adhesive
The adhesive layer of this system also contains the drug. In this
type of patch the adhesive layer not only serves to adhere the various
layers together, along with the entire system to the skin, but is also
responsible for the releasing of the drug. The adhesive layer is
surrounded by a temporary liner and a backing
• Multi-layer Drug-in-Adhesive
is similar to the single-layer system in that adhesive layers are also
responsible for the releasing of the drug. One of the layers is for
immediate release of the drug and other layer is for control release of
drug from the reservoir. The multi-layer system is different however
that it adds another layer of drug-in- adhesive, usually separated by a
membrane .
•
•
•
•
•
Rate controlling factors include:
Thickness of adhesive layer
Polymers: crosslinked gelatin , lecithin
Advantages:
A system in which the drug is incorporated directly into the
adhesive, rather than into a separate layer. Usually used for
smaller molecular weight compounds.
• Iontophoretic patches use a tiny electrical current run
through a drug containing electrode in contact with the skin
to promote flow of the drug (usually charged) through the
skin.
• The most popular electrodes are based on the silver/silver
chloride redox couple.
Three main mechanisms enhance molecular transport:
1. Electro-repulsion Charged species which driven primarily
from the driving electrode.
2. Flow of electric current may increase the permeability of skin
3. Electro osmosis affect uncharged molecules and large polar
peptides.
Limitations: Hair follicle damage is possible.
The mechanism of iontophoresis
Mechanism is based on the physical phenomenon that “like charges
repel and opposite charges attract”. The drugs are forced Across the
skin by simple electronic repulsion of similar charges. Thus, anionic
drugs Can cross the skin by using a negatively charged electrode.
Similarly, cationic drugs enter the skin when a positively charged
electrode is used.
While delivering a negatively charged drug across skin, it is placed
between the negative electrode (cathode), and the skin. The drug ion
is then attracted through the skin towards the positive electrode
(anode) by the electromotive force provided by the cell. In case of
positively charged drug, it is placed between the positive electrode
(Anode), and the skin. Once the drug has passed through the outer
barrier layer of skin, it reaches to its site of action by rapidly going into
the circulation.
• The system fires solid particles (20–100µm) through
stratum corneum into lower skin layers, using a supersonic
shock wave of helium gas. Intraject is a development of
the vaccine gun designed to deliver liquids through skin
without using needles.
• Advantages :
• Pain-free delivery — particles are too small to trigger pain
receptors on the skin.
• Improved efficacy and bioavailability.
• Targeting to a specific tissue, such as a vaccine delivered
to epidermal cells.
• Accurate dosing and Overcomes needle phobia.
• Safety — the device avoids skin damage or infection from
needles or splash back of body fluids.
• A device containing 400 solid or hollow silicon needles,
approximately 150 μm in length, that penetrate through the
stratum corneum into the upper epidermis
• When a current is passed through the PCB heater the
composite heat up and expands into the liquid reservoir,
consequently ejecting through the hollow microneedles.
Advanteges:
• Microneedles patches are currently being explored as
mechanisms to deliver vaccines and larger macromolecules.
• Pain-free delivery — microneedles are too small to trigger
pain receptors on the skin.