methods of formulation, evaluation and iontophorosis

4. Advantage:
1. Avoidance of first pass effect
2. Stable and controlled blood level
3. Comparable characteristics with intravenous
infusions.
4. Long term duration
5. No interferance with gastric and intestinal fluids.
6. Administer drugs with very short half life,
narrow therapeutic window and poor oral
absorption.
7. Improved patient compliance.
8. Self administration is possible.
9. Systems are noninvasive.

5. Limitations:
1. Drug must have desirable physicochemical
properties for permeation through stratum
corneum.
2. Skin irritation or contact dermatitis due to
drug or excipients.
3. Barrier function of skin changes from one
site to another on the same person, person-
to-person and with the age of person.

10. PERMEATION OF DRUG MOLECULE THROUGH SKIN
• It express by Fick’s first law of Diffusion-Drug
molecule diffuse from a region of higher conc.
to one of lower conc. until equilibrium is
attained.
• The process of Diffusion of molecule is driven
by gradient between high concentration to low
concentration.
10

11. PERCUTANEOUS ABSORPTION

12. • Percutaneous absorption done by 2-ways-
A. Transepidermal Absorption
Stratum
Corneum
Intracellular
Pathway
Intercellular Pathway
Viable Epidermis
Dermis
Microcirculation

14. • B. Transfollicular Absorption
Pilosebaceous
unit
Eccrine Gland
Hair Follicles Sebaceous Gland
Dermis
Microcirculation

15.  Skin appendages offer only secondary route
of permeation.
 The follicular route is important route of
percutaneous absorption since the opening
of follicular pore where the hair shaft exits
the skinis relatively large and sebum aids in
diffusion of penetrants.

16. Steps involved in transdermal permeation of
drug:-
1. Sorption by stratum corneum
2. Penetration of drug through viable epidermis
3. Uptake of drug by capillary network in the
dermal papillary layer.

17.  Physicochemical property of Drug molecule,
 Partition co-efficient,
 pH Condition,
 Drug Concentration
 Physicochemical property of Drug Delivery
System,
Release characteristics,
Use of permeation enhancer,
Composition of Drug Delivery System.
17

18.  Pathophysiological condition of Skin,
Reservoir effect of Horney Layer,
Hydration of skin,
Lipid Film,
Skin Temperature,
18

19. 1. Partition coeff. : Drugs possessing both water and lipid
solubilities are favored .
 Lipid/water partition coeff. of 1 or more is required for
optimal transdermal permeability.
2. pH conditions: pH conditions of skin and in drug delivery
system affect dissociation and permeation of drug molecule.
3. Drug concentration: permeation is passive diffusion process
hence depends on drug conc. on surface of skin layer.
 more drug is absorbed through percutaneous absorption
when the drug is applied to a large surface area.
 Drug incorporated in an appropriate vehicle must interface
skin in sufficient concentration.

20. 1. Release characteristics: generally the more easily the
drug is released from delivery system, the higher the
rate of permeation.
 Drug subs. should have greater physicochemical
attraction to skin than to vehicle in which it is
presented in order for the drug to leave in favor of the
skin.
 Mechanism of depends on interfacial partition coeff. of
drug from delivery system to skin tissue.
2. Composition of drug delivery system: it has great
influence on absorption.
 It not only affect release rate but also permeability of
stratum corneum by means of hydration, mixing with
skin lipids or other promoting effects.

21. 3. use of permeation enhancers: permeation can be
improved by use of sorption or permeation
promoters.
 Drug absorption enhanced by the vehicles that
easily cover the skin surface, mix readily with
sebum and bring drug in contact with sebum for
tissue absorption.

22. 1. Reservoir effect of horny layer: horny layer or its
deep layer can act as depot or reservoir.
 Absorption appears to be greater when drug is
applied to skin with thin horny layer than with one
that is thick. thus, site of application affect degree
of drug absorption.
 Generally, longer the period of time of medicated
application is permitted to remain in contact with
skin, the greater will be the absorption.

23. 2. Vehicles that increase amount of moisture imbedded
by the skin generally favor percutaneous absorption of
drug. Oleaginous vehicles acts as moisture barrier
through which the sweat from the skin cannot pass and
skin therefore remain occluded resulting in increased
hydration of skin beneath the vehicle.
3. Skin hydration: imp factor of absorption.
 hydration of stratum corneum appears to increase rate
of passage of certain substances that penetrate the
skin.
 Increased absorption is probably due to softening of the
tissues and the consequent sponging effect with an
increase in size of the pore allowing greater flow of
substance, large and small molecules through them.

24.  Hydration of stratum corneum can enhance the
permeability of skin by as much as eight folds.
4. Skin temperature: skin permeation of acetyl
salicylic acid and glucosteroids was raised ten folds
when the environmental temp was raised from 10-
37 °C.

30. Permeation enhancers may be:-
1. Solvents: increase penetration by swelling the polar
pathway.
Eg, alcohols, dimethylsulfoxide (DMSO),
dimethylformamide, 2-pyrrolidone etc.
2. Surfactants: enhance polar pathway transport of
hydrophillic drugs. Eg, sodium lauryl sulfate,
Pluronic F127, Pluronic F68
3. Bile salts: sodium deoxycholate, sod.
taurocholate.

34. A. Rate-Programmed
Systems
 Drug in Reservoir
 Drug in Matrix
 Drug in Adhesive
 Drug in
Microreservoir
34
B. Physical Stimuli-
Activated Systems
Iontophoresis

35. 1.Drug in Reservoir
A.RATE-PROGRAMMED SYSTEMS-
-Drug reservoir is embedded between an impervious
backing layer and a rate controlling membrane.
-Drug release only through the rate controlling
membrane.
-In drug reservoir compartment, it can be in the form of
solution, suspension or gel or dispersed in a solid polymer
matrix.
-On the outer surface of polymer membrane a thin layer

36. 2.Drug in Matrix
•The drug is dispersed homogenously in a
hydrophilic or lipophilic polymer matrix.
•This drug containing polymer layer is then fixed
onto an occlusive base plate in a compartment
fabricated from a drug impermeable backing layer.
•Instead of applying adhesive on the face of the drug
reservoir, it is spread along the circumference to
form a strip of adhesive rim.

37. 3.Drug in Adhesive
Here, adhesive layers are also responsible for
releasing of drug.
Drug reservoir is formd by dispersing drug in
adhesive polymer and then spreading medicated
polymer adhesive by different methods on
impermeable backing membrane.

38. 4.Drug in Microreservoir
-It is a combination of reservoir and matrix dispersion
system.
- For drug reservoir, the drug is first suspended in
aqueous solution of water soluble polymer and then
dispersing the solution homogenously in lipophillic
polymer to form thousands of unleachable, microscopic
spheres of drug reservoir.

39. B. Physical Stimuli-Activated Systems-
1. Iontophoresis-
It involves transport of ionic or charged molecules
into a tissue by a passage of direct or alternating
electric current through electrolyte solution
containing the ionic molecules to be delivered.
It involves electromotive force for transfer of ions.

40.  Ions with positive charge are driven into the skin at
the anode and those with negative charge at the
cathode.
 Drug is administered through an electrode having
same charge as that of drug and a return electrode
opposite to charge of drug.
 Operator then selects current intensity below the
pain threshold level of the patient and allows the
current to flow for an appropriate period of time.
 Current intensity should be increased slowly ,
maintained for the length of the treatment and
then slowly decreased at the end of the treatment.
 Current must be between the tolerance of the
patient with a current density less than 0.5
m.amp/cm2 of the electrode surface.

41.  Placing a moist pad between electrode plate and
the skin is necessary for making perfect contact,
preventing any skin burns, overcoming skin
resistance and protecting the skin from absorbing
any caoustic metallic compound formed on the
metal plate surface.
 The drug should be applied through the electrode
with correct polarity , since any reversal of polarity
may result in no penetration of the drug.

42. 1. Evaluation of Adhesive
a. Peel Adhesion Properties-
 It is the force required to remove coating from a test
substrate.
 peel adhesion properties are affected by molecular
weight of adhesive polymer , type and amount of
additives ad polymer composition.
42

43. Tack Properties- It is the ability of polymer to adhere
to a substrate with little contact pressure.
 Thumb tack test- press thumb briefly on the
adhesive.
 Rolling ball tack test – measurement of distance
that a stainless steel ball travels along an upward
facing adhesive.
the less tacky the adhesive, father the ball will
travel.

44.  Quick-Stick test/ peel tack test- peel force
required to break he bond between the adhesive
and substrate is measured by pulling the tape
away from substrate at 90° at speed of 12
inch/min.
force is recorded as tack value and expressed in
ounce per inch width.

45.  Probe tack test: force required to pull a probe away
from the adhesive at a fixed rate is recorded as tack.

46. c. Shear Strength Properties-
It is the measurement of the cohesive
strength of an adhesive polymer.
Shear strength is determined by measuring
the time it takes to pull an adhesive coated
tape off a stainless steel plate when a
specified weight is hung from the tape
which pulls tape in a direction parallel to
the plate.

47. A. In vitro Permeation
Studies-
 In-Vitro skin Diffusion cells
B. In vitro Release Studies-
 Paddle Over Disc Apparatus (USP Apparatus 5)
 Reciprocating Disc (USP Apparatus 7).
47