Transdermal Drug Drlivery System

Question 1

Define transdermal drug delivery system

Answer 1

Are systems that Utilize skin as a site for continuous drug administration into the systemic circulation

Question 2

Advantages of TDD’s

Answer 2

Bypasses first pass hepatic metabolism
Decrease side effects
Maintains constant blood levels for longer period of time
Increase patient compliance
Maintains constant blood levels for longer period of time
Easy to discontinue in case of toxic effects

Question 3

Disadvantage of TDD’s

Answer 3

Local irritation at the site of administration may be caused by excipients /adhesives
TDD can’t deliver ionic drug
TDD can’t achieve high drug levels in Blood/plasma
Drug of large molecular size can’t be formulated as TDD
TDD can’t deliver the drugs in pulsation fashion

Question 4

List skin structure

Answer 4

1. Epidermis - stratum corneum, stratum spinosum, stratum granulosum, statum lucidum
   2.Dermis
2. Subcutaneous

Question 5

Describe stratum corneum, viable epidermis, viable dermis(cornium), subcutaneous connective tissue (hypodermis)

Answer 5

1.outer most layer of skin , physical barrier(stratum corneum)
2.layer between stratum corneum and dermis(viable epidermis)
3.consists of matrix of loose connective tissue composed of fibrous protein(cornium)
4.contains blood, lymph vessels, base of hair follicles , secretory portion(hypodermis)

Question 6

Routes of drug penetration across skin(macro)

Answer 6

Macro routes- via sweat ducts, across the continuous stratum corneum(diffusion) , through hair follicles with their associated sebaceous glands

Question 7

Routes of drug penetration across skin

Answer 7

1.transcellular permeation-through stratum corneum
2.intracellular permeation-through stratum corneum
3.Transappendageal permeation via hair follicle , sebaceous and sweat gland(allow diffusional leakage of polar molecules into epidermis and direct permeation into dermis)

Transcellular and intercellular permeation requires diffusion through epidermis and dermis

Question 8

Give factors that affect routes of drug administration

Answer 8

Physiochemical properties - pKa, molecular size, stability
Integrity and thickness of stratum corneum
Density of sweat glands and follicles
Skin hydration
Metabolism and vehicle effects

Question 9

Factors influencing dermal penetration of drugs

Answer 9

Biological factors- blood flow, skin age, skin condition, skin metabolism,
Physiochemical factors -skin hydration , temperature and pH, drug concentration, molecular size and shape, solubility and ionization

Question 10

Fundamentals of skin permeation

Answer 10

See formula

Question 11

Mechanism of precutaneous drug absorption

Answer 11

Transepidermal pathway responsible for drug diffusion across skin through partition into stratum corneum.Extremely polar compounds and ions pass by microscopic path through stratum corneum and lipophilic molecules concentrate in and diffuse easily through horny layers.Enters viable epidermis and both extremely hydrophilic and hydrophobic have difficulty passing through viable epidermis as cell membranes are tightly joined

Question 12

Describe transaapendageal route

Answer 12

Waiter soluble substances are diffused faster through appendages . Sweat glands and follicles act as shunts. The follicular pore is large and sebum aids in diffusion of penetrant then diffusion to depths of epidermis

Question 13

Factors affecting transdermal permeability

Answer 13

Partition coefficient, drugs with both water and lipid solubility are favorably absorbed . A lipid/water partition of 1 or greater is generally required for optimal transdermal permeability
Increase conc of drug in vehicle increases amount of drug absorbed per unit of surface area per time interval
Surface area more drug is absorbed when applied to large surface area
Drug should have greater Physiochemical attraction to skin than to diapered vehicle

Question 14

Give benefits if oleaginous vehicles

Answer 14

Increase amount of moisture imbedded by skin to improve drug absorption
Ie hydration of skin-softens stratum cornium , increased size of pores allowing greater flow of substances
Also longer contact period of drug with skin greater will be absorption

Question 15

Permeation enhances

Answer 15

Promote skin permeability by altering skin barrier to the flux of desired penetrant
Classier as :solvents , surfaces , miscellaneous chemicals

Question 16

List materials /components/ formulation of transdermal patch

Answer 16

Polymer matrix
The drug
Pressure sensitive adhesives
Permeation enhancers
Excipients

Question 17

Ideal characteristics of polymer matrix

Answer 17

Stable and non reactive with the drug
Polymer and it’s degradation products must be non toxic or non antagonistic to the host
Mechanical properties of polymers should not deteriorate excessively when large amount of active agents are incorporated into it

Question 18

Examples of polymers used in TDD

Answer 18

Natural polymers - gelatin, waxes, proteins
Synthetic elastomers -nitrile, butyl rubber , neoprene
Synthetic polymers-polyvinyl chloride , polyethylene, poly propylene

Question 19

Physiochemical properties of the drug

Answer 19

Non-ionic
Low molecular weight
Low melting pint
Potent
Aq solubility in oil and water

Question 20

Biological properties of drug

Answer 20

Half life of drug should be short
Tolerance of drug must not be developed
Drug mustn’t induce cutaneous irritant or allergic response

Question 21

Ideal properties of pressure sensitive adhesives

Answer 21

Shouldn’t irritate or sensitize skin
Should adhere to skin aggressively shouldn’t be removed easily
Permeation of drug should be affected

Question 22

3 classes of pressure sensitive adhesives

Answer 22

1. Polyisobutylene based adhesive - good for low solubility and polarity drugs
2. Acrylic -they are moderately polar and have moisture permeability
3. Silicon based adhesives-have high permeability to moisture and oxygen which reduces degreee of oclusion

Question 23

Permeation enhancers ideal properties

Answer 23

Work rapidly
Shouldn’t have pharmacological activity
When removed barrier properties should return rapidly and fully
Activity and duration of effect should be both predictable and reproducible

Question 24

Permeation enhancers act through 3 possible mechanisms

Answer 24

1. Disrupt statum corneum lipid organization making it permeable and increases drug diffusion coefficient ex oleic acid and terpenes these form permeable pores to allow access to viable epidermis for polar molecules
   2.enhancers interact with keratin in corneocytes to open up dense protein structures and make them more permeable ie ionic surfactants
2. Many solvents enter stratum corneum changes it’s solution properties by altering the chemical env and increasing partitioning of second molecule in the horny later ie ethanol increases penetration of nitroglycerin

Question 25

Job of permeation enhancers

Answer 25

Act on skin to improve drug diffucibilty/solubility/both DSMO and axons can increase diffusability in stratum corneum by acting as solvents to dissolve skin lipids to denature skin proteins Ethanol, ketones, lactones can modify drug solubility parameters , partition coefficient from vehicle to skin

Question 26

Speak on solvents, surfactants

Answer 26

Solvent- increase penetration by swelling polar pathway transport je water, ethanol Surfactants -enhance polar pathways transport of hydrophilic drugs ie anionic surfactants-SLS

Question 27

Give examples of excipients/other supportive materials

Answer 27

Release liner-prevents loss of drug that has migrated through adhesive layer during storage and protects against contamination ex: metal foils Backing layer-prevent drug from leaving the dosage form from the top ex: metallic plastic laminate Microporous or semi permeable - used to limit the flow of drug from both the reservoir and matrix systems ex:ethylene vinyl acetate membranes Packing substance- for stability and integrity

Question 28

3 main layers used for pouches

Answer 28

External printable layer Aluminum foil layer Internal plastic heat sealable layer

Question 29

List 4 types of TDDs

Answer 29

Single layer drug in adhesive Multi layer drug in adhesive Drug reservoir in adhesive Drug matrix in adhesive r

Question 30

Single layer drug in adhesive

Answer 30

Inclusion of drug directly within skin - contacting adhesive. Serves as for lunar ion foundation containing drug and all excipients under a single backing film

Question 31

Multi layer drug in adhesive

Answer 31

Drug is incorporated directly into the adhesive Multi- layer encompasses either the addition of membrane between 2 distinct drug in adhesive layer or addition of multiple drug in adhesive layer under a single backing film

Question 32

Drug reservoir in adhesive

Answer 32

Inclusion of a liquid compartment containing a drug solution/suspension separated from release liner by semi -permeable membrane and adhesive

Question 33

Drug matrix in adhesive

Answer 33

Inclusion of semi solid matrix containing a drug solution or suspension which is in direct contact with release liner The component responsible for skin adhesion is incorporated in an overlay and forms concentric configuration around semisolid matrix

Question 34

Evaluation of TDDs

Answer 34

Physical -film thickness, tensile strength Weight variation Drug content % of moisture content % of moisture uptake Adhesive evaluation Skin uptake and evaluation

Question 35

Criteria to asses physical evaluation

Answer 35

Film thickeners %of flatness- is equal to average %length after cut 3 strips of 7cn of short form film length measure with out applying pressure Tensile strength - measure force required to break the system

Question 36

Weight variation

Answer 36

Weigh randomly selected 19 patches and calculate avg and %of weight variation

Question 37

%moisture contents

Answer 37

Initial weight of film , store in dedication with activated silica , room temo . 24h. Repeatedly weigh film until constant weight

Question 38

Adhesive evaluations

Answer 38

Peel adhesion test -force required to remove adhesive coating from test substrate it is tested by measure ig force required to pull single coated tape applied to a substrate at an 180degree angle. If higher value indicates good bond strength

Question 39

Under adhesive evaluation also have tack properties

Answer 39

Tack being ability of polymer to adher to substrate with little contact pressure 1. Thumb tact test-briefly press thumb into adhesive 2Rolling ball tack test 3. Quick -stick test 4. Probe tack test

Question 40

In vitro drug release evaluation

Answer 40

Franz-diffusion cell . Consist of permeation area of 1cm2 and receptor cell volume and bar magnet for stirring solution in receptor compartment