Patches

Question 1

Objective of Dermal Therapeutic Systems (DTS)?

Answer 1

maximize delivery of drugs into the SC, upper epidermis, or dermis and at the same time minimize further absorption into the systemic circulation
used for local skin conditions

Question 2

Advantages of DTS

Answer 2

More uniform delivery (local anesthetics)
Longer duration (ability to retain drug in the stratum corneum longer (eg. Salicylic acid for warts and calluses)
Substantivity (resistance to wash-off the active during showering/swimming)
Deeper penetration (local anesthetics, anti-inflammatory agent, analgesics-->under occlusion)
Reduced side effects (reduces irritation due to lower dose

Question 3

Examples of DTS use

Answer 3

treatment of corns, calluses, and warts 
Pain-relief 
occlusive dressings 
antimicrobial agents 
non-invasive diagnostic patches

Question 4

Objectives of TTS

Answer 4

Delivery and maintenance of therapeutic levels of drug in the systemic circulation over a long period of time with the most convenience to the patient
Drug has to get into the bloodstream to get to the systemic circulation

Question 5

What is the rate-limiting step of TTS

Answer 5

Diffusion across the SC is still the rate-limiting step

Question 6

advantages of TTS

Answer 6

No need for frequent dosing: more convenient
Have better patient adherence
Avoid GI irritation, good if the patient cannot swallow
Avoids first-pass metabolism (advantage for drugs that undergo extensive metabolism)
Multi-day therapy can be achieved by a single application
Easy to terminate the drug effect: just remove the patch

Question 7

disadvantages of TTS

Answer 7

Local site irritation: from active ingredient or excipient in the patch
Other people can see the patch
Patches can only be applied to certain areas of the body
Structure of the drug comes in because drugs that arent lipophilic enough to penetrate the SC
Onset of the drug may be slower than other dosage forms
Skin conditions affect the rate of absorption (only apply to healthy skin)
Can only incorporate drugs that are potent (cannot have too large of a dose)

Question 8

Drugs that make good candidates for TTS

Answer 8

Drug with high potency (dose requirement of less than 25mg/day)
Low molecular weight
Lipophilic
Small half-life
Low melting point
High skin permeability
Non-irritating and non-sensitizing to the skin
Low oral bioavailability
Small therapeutic index (requires tight control of plasma levels)

Question 9

Examples of TTS

Answer 9

Female reproductive hormonal therapy (menopausal, postmenopausal, contraceptive)
Cardiovascular system disease (angina, HTN)
Pain control (chronic pain)
Treatment of certain allergies (OTC antihistamine)
CNS disorders (motion sickness, Parkinson’s syndrome, Alzheimer)
Smoking cessation

Question 10

what are the types of TTS

Answer 10

Reservoir Type
Matrix Type
Drug-in-adhesive (DIA)
Dot-matrix

Question 11

What is in the drug compartment of reservoir type patches

Answer 11

contains drug solution or suspension in reservoir space

Formulation contains: Drug dissolved/suspended in solvent, liquid excipients, penetration enhancer

Question 12

How is drug delivery controlled in a Reservoir type

Answer 12

rate controlling membrane
shows zero-order release kinetics (higher concentration of drug doesnt mean the drug will have a high rate of absorption)

Question 13

Where is the adhesive located in reservoir type patches

Answer 13

Mostly a continuous layer on the membrane (face adhesive)

Or in a concentric configuration on the perimeter of the patch

Question 14

Disadvantages to reservoir type patches

Answer 14

Adhesive and drug or adhesive and excipient interactions/incompatibilities can occur
Vulnerable to dose dumping (cannot cut the patch, can rupture the membrane due to material defect, or inadvertent puncture)

Question 15

Examples of reservoir type patches

Answer 15

Estraderm (menopausal symptoms)
Estracomb (birth control) 
Transderm-Nitro (nitroglycerin for angina) 
Duragesic (fentanyl for chronic pain) 
Androderm (testosterone)

Question 16

What is in the drug compartment of the matrix type patch

Answer 16

Contains drug solution or suspension form in a matrix
Most simple design: a drug containing semisolid disc is held in contact with the skin by an adhesive tape
formulation contains (drug dissolved/suspended in semisolid and penetration enhancer)

Question 17

how is the drug delivery controlled in a matrix type patch

Answer 17

rate controlling matrix and the SC
follows first order kinetics
NO membrane

Question 18

what is the location of the adhesive in the matrix type patch

Answer 18

Mostly in a concentric configuration on the perimeter of the patch The drug doesn’t come into contact with the adhesive (this gives more flexibility for excipient selection)

Question 19

Disadvantages of matrix type patches

Answer 19

The protective overlay may be mistaken for the part to be applied on the skin
Total patch surface area can be a lot longer then the actual drug delivery surface
Matrix is large and stiff therefore very visible

Question 20

examples of matrix type patches

Answer 20

Nitrodisc (nitroglycerin for angina)
Prostep (nicotine for smoking cessation)
Exelon (alzheimers)

Question 21

what is in the drug compartment of Drug-in-adhesive (DIA) type patches

Answer 21

Contains the drug dissolved in an adhesive formulation
Formulation contains drug dissolved in a pressure sensitive adhesive (PIB, silicone, or acrylate type)
Adhesive composition must be customized for each drug

Question 22

advantages of DIA patches

Answer 22

extremely comfortable

maximum utilization of surface area of the patch

Question 23

How is the drug delivery controlled in DIA type patches

Answer 23

rate controlling adhesive and the SC
show first-order kinetics
NO membrane

Question 24

what is the multi-laminate design

Answer 24

used where more drug can be released through the membrane in the upper DIA compartment into the lower DIA compartment

Question 25

Disadvantages of DIA

Answer 25

□ The first-order release characteristics (when drug concentration in adhesive falls, constant drug delivery profile is difficult to maintain) to overcome this problem

Question 26

Examples of DIA

Answer 26

Nitro-Dur
Estalis (combination estrogen)
Estradot
Transderm-Scop (motion sickness)

Question 27

What is in the drug compartment of the dot matrix type patch

Answer 27

Acrylic: to hold the drug in high concentration
Semisolid suspension: the microscopic drug-in acrylic droplets evenly dispersed in the non-compromised silicone adhesive
Formulation contains (Drug dissolved in acrylic and Adhesive: silicone)

Question 28

What are some ways patches can be improperly applied

Answer 28

Peeling not just the protective layer but the adhesive overlay
Should be applied directly on the skin (a patient once had 4 patches on top of each other)
Must remove the protective liner
Location where the patch should be applied (number of blood vessels differs based on where in the body so the sink effect differs, thickness of the SC also differs)
One patch at a time (old patch isnt removed when the new one is applied)
Clear patches are difficult to find on the body when it is time to remove

Question 29

Other issues with patches

Answer 29

Nomenclature issues 
Differing dosing intervals 
Physician errors (dosing interval confusion, duplicate therapy with 2 dosage forms of the same drug) 
Pediatric patch issues (cannot cut reservoir type but can be done with matrix of DIA types)

Question 30

How to apply a patch

Answer 30

Apply to non-hairy areas (increases drug absorption through the hair follicle and the patch may not adhere to the skin as well)
Site of application should be dry–>don’t use in sauna/hot/humid place
Remove the old patch before applying the new patch
Don’t apply to areas with cuts/skin damage
Don’t apply below the knee or elbow ( vascularization might be different which results in a different sink effect which results in varying drug concentrations
DON’T TAKE HOT SHOWERS)