Download Adhesive diffusive controlled systems

TRANSDERMAL DRUG
DELIVERY SYSTEMS
Department of Pharmaceutics
TRANS DERMAL DRUG DELIVERY SYSTEMS
DEFINITION:
TDDS are adhesive-drug containing device of defined
surface area that deliver a predetermined amount of drug to
the surface of intact skin at programmed rate to reach the
systemic circulation
Advantages
• Self administration is possible and Continuous, sustained release
of drug
• multiday dosing interval
• Avoids first-pass hepatic metabolism and enzymatic degradation
by gastrointestinal tract
• Less frequent dosing improves patient Compliance
• Alternate route for patients who are unable to take oral
medications
• Dose delivery unaffected by vomiting or Diarrihoea
• Drug administration stops with patch removal
Disadvantages
• Only small, lipophillic drugs can be delivered currently
through the skin
• Not suitable for high drug doses
• Adhesion may vary with patch type and environmental
conditions
• Skin irritation and hypersensitivity reactions may occur
• The barrier function of the skin changes from one site to
another on the same person, from person to person and with
age
The skin is one the most extensive organs of the human body covering an
area of about 2m2 in an average human adult.
The skin separates the underlying blood circulation network from the
outside environment
Anatomically, the skin has many histologic layers but in general, it is
described in terms of three major tissue layers:
The epidermis,
The dermis and
The hypodermis
.
There are critically three ways in which a drug molecule can cross the
intact stratum corneum:
(a)through the walls of the hair follicles,
(b) through the sweat glands or the sebaceous glands,
(c) or between the cells of the horny layer
BASIC COMPONENTS OF TDDS
The components of transdermal devices include:
Polymer matrix
Drug
Drug permeation enhancers
Other excipients
1. POLYMER MATRIX
The polymer controls the release of the drug from the
device.
Materials used for polymer matrix:
Natural polymers
Cellulose derivatives, Zein, Gelatin, Shellac, Waxes, Proteins, Gums
and their derivatives, Natural rubber, starch etc.
Synthetic elastomers
Polybutadiene, Hydrin rubber, Polysiloxane, Silicone rubber, Nitrile,
Acrylonitrile, Butyl rubber, Styrenebutadiene rubber, Neoprene
etc.
Synthetic polymers
Polyvinyl alcohol, Poly vinyl chloride, Polyethylene, Polypropylene,
Polyacrylate, Polyamide, Polyurea, Polyvinylpyrrolidone,
Polymethylmethacrylate, etc.
2.DRUG
Ideal properties of drug for TDDS
Dose Should be low (less than 20mg/day)
Half-life 10/less (hrs)
Molecular weight < 400 Da
Partition co-efficient (octanol-water) between 1.0-4.0
Skin permeability coefficient > 0.5×10-3 cm/h
Skin reaction Non irritating and nonsensitizing
Oral bioavailability Low
Therapeutic index Low
Melting Point < 2000F
pH Between 5.0-9.0
3. PERMEATION ENHANCERS
These are compounds which promote skin permeability by altering the
skin as a Barrier to the flux of a desired penetrant
surfactants,
azone,
dimethylsulfoxide (DMSO),
dimethylacetamide,
dimethylformamide,
alcohol,
acetone,
propylene glycol, and
polyethylene glycol.
APPROACHES FOR DEVELOPMENT OF TDDS
Membrane moderated systems
Adhesive diffusive controlled systems
Matrix dispersion type systems
Micro reservoir systems
Membrane moderated systems
The intrinsic rate of drug release from this type of drug delivery system is defined by
Cr
dq/dt =
1/Pm + 1/Pa
Pm=Km/r(Dm/δm)
pa =Ka/m(Da/ δa)
where
Cr- is drug concentrate in the reservoir compartment.
Pa & Pm- are permeability coefficients of the adhesive layer and the rate controlling
membrane respectively
Adhesive diffusive controlled systems
The rate of drug release is defined release is defined by
dq /dt = Ka/r Da Cr
δa
where
Ka/r is partition coefficient of drug from the reservoir layer
to the adhesive layer.
Matrix dispersion type systems
Rate of drug release from this matrix dispersion type TTS is defined as
dq/dt = (ACp Dp/ 2t)1/2
where
A -is initial drug loading dose dispersed in the polymer matrix.
Cp and Dp- solubility and diffusivity of the drug in the
polymer respectively.
Micro reservoir systems
The rate of release of drugs from the microreservoir system is defined by
dQ/dt = Dp.Dd.m.kp/Dp.hd+Dd.hp.m.kp
EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEMS
1.Evaluation of adhesive
Pressure sensitive adhesives are evaluated for the following
properties
a.Peel adhesion properties
b.Tack properties
Tack is the ability of a polymer to adhere to a substrate with little
contact pressure. It is important transdermal devices which are applied
with finger pressure.
Tests for tack include
i.Thumb tack test
This is a subjective test evaluation is done by pressing the thumb briefly
into adhesives. Experience is required for using this test.
ii.Rolling ball tack test
iii.Quick-stick (or peel-tack) test
iv.Probe tack test
c.Shear Strength Properties
2.In-vitro drug release evaluation
 8 – Cell Trans Diffusion Cell
 Keshary Chein Diffusion Cell
 Franz Diffusion Cell
Franz Diffusion Cell
3.In-vivo evaluation
In vivo evaluation of transdermal drug delivery systems can be carried
out using:
a. Animal models
b. Human volunteers
c. Biophysical models
Marketed Products of Transdermal Patches
Brand Name
NicotinellR
NuPatch 100
Alora
Androderm
Drug
Nicotine
Diclofenac
diethylamine
Estradiol
Manufacturer
Novartis
Zydus Cadila
TheraTech/Proctol and
Gamble
Testosterone
Nitroglycerin
Catapres TTSR
Clonidine
OxytrolR
oxybutynin
Pharmacological
smoking
cessation
Anti Inflammatory
Postmenstrual
syndrome
Hypogonadism in
TheraTech/GlaxoSmithKl
ine
Nitrodisc
Indications
Roberts
Pharmaceuticals
Alza
Watson Pharma
males
Angina pectoris
Hypertension
Overactive bladder
REFERENCES
•Chein YW. Transdermal Controlled Systemic Medication. New
York and Basel, Marcel Dekker Inc. 1987; 159 – 176
•http://www.pharmainfo.net
•http://en.wikipedia.org/wiki/Transdermal_patch
•http://www.bentham.org/cdd/sample/cdd2-1/003AP.pdf
•http://molinterv.aspetjournals.org/content/4/6/308.full
•http://www.docoop.com/drug-delivery/drug-deliverysystems.asp