PHARMACEUTICS 2: TRANSDERMAL SKIN PATCHES EXAM 1

what type of absorption does the skin use?

percutaneous absorption

what is percutaneous absorption? what is the goal?

it is absorption through the skin. the goal is for thr drug to reach systemic ciruclation through the skin

what are the 4 functions of the skin?

protection, thermoregulation, sensory organ, and endocrine functions sucha s vitamin d synthesis

why is knowing that the main function of the skin is protection important wjen delivering a drug through the skin?

when delivering a drug through the skin we have to break some of the barriers of protection

how is a drug topically delivered? where does it go?

it is delivered locally on the skin. it stays in a particular region of the body. it stays on top of the skin

what is the goal of transdermal delivery?

the goal is for the drug to reach the blood circulation

why is it important that a transdermal drug penetrates through the skin into blood circulation in terms of localized vs non localized effect?

when the drug reaches systemic circulation it has a systemic effect across the whole body

what are the main differences between topical and transdermal deliveries?

topical is local and doesnt go into blood stream, transdermal goes into the blood stream which makes an effect across the whole body

what is the stratum corneum composed of?

composed of dead cells 

what is the dermis composed of?

composed of blood vessels, nerves, hair follicles, and sweat glands

why if you damage the stratum corneum will you not feel any pain?

this is because it is a avascular layer. there is no blood vessels or nerve endings here

what is the 2 main functions of the stratum corneum?

it prevents the loss of water from the body and acts as a barrier for the penetration of any foreign objects such as a drug

"what are the ""bricks"" of the stratum corneum?"

corneocytes

what do corneocytes do in the stratum corneum?

they contain water and moisturizing factors which helps retain water

what component in the stratum corneum is the hydrophobic component?

the bound lipid component

what holds the corneocytes together in the stratum corneum? why is this important?

intercellular lamellar lipid (mortar) holds the lipids together which is important because it provides a continous pathway for lipid components to penetrate into the skin

how does anything that is hydrophilic go through the stratum corneum?

anything that is hydrophilic will go through carneocytes which is a discontinous pathway not directly connected to each other. so the substance has to partition between hydrophobic and hydrophilic regions

what way do drugs go through the stratum corneum?

passive diffusion

what is the major barrier for percutaneous absorption?

stratum corneum

describe the surface of the stratum corneum

the surface is covered with a film of sweat, sebum, and epidermal cells. it is 40% water, 40% proteins, and 20% lipids

what does the rate of drug absorption in the stratum corneum depend on?

it depends on the concentration of drug in the vehicle (concentration of drug on the skin or where the drug is coming in contact with the skin), aqeuos solubility of the drug (solubility in water and lipid phase), and oil/water partition coefficient

what are the 4 different routes a drug can penetrate through the skin?

intercellular pathway, transcellular pathway, polar pores pathway, and pilosebaceic pathway

what is the intercelluar pathway?

drug goes through the intercellular lipids

what is the transcellular pathway?

passing through keratinocytes or carneocytes

what is the polar pores pathway?

aqeous islands present between cells surrounded by lipids

what is the pilosebaceic pathway?

going through a skin opening such as a hair follice

what are the steps in percutaneous absorption of a drug?

the drug is applied onto the skin, it goes through the stratum corneum, goes through the epidermal tissues and vascular dermal layer and then gets absorbed into the blood

how does a drug partition through the stratum corneum?

the stratum corneoum is predominantly water so the drug partitions into water then it partitions into lipids in the epidermal membrane and then it partitions into water and goes into the blood

what are the factors that effect percutanous absorption?

molecular weight, solubility, high partition coefficent, pka, polarity of drug, drug concentration, and area of application

how does molecular weight affect percutanous absorption? what is the ideal size?

the drug should be between 100 to 800 daltons ideally but most drugs are less than 400 daltons. this is because too large molecules will not go through pasive diffusion

why is solubility important in percutaneous absorption?

the drug must be soluble in both lipids and water. if its only lipid soluble it will stay in the lipid component of the skin so it will not reach the blood

what must the parititon coefficent be and why?

it must have a log P between 1 and 4 because it needs to be soluble in both oil and water 

why does pka matter in percutaneous absorption? (ionzied or unionized)

unionized penetrates faster than ionized form because passive diffusion works bettger with unionized drugs

why does polarity of drug matter in percutnaeous absorption?

non polar absorbs better than polar because of the continous lipid pathway. non polar drugs easily follow the pathway. a polar durg has to partition through cells

why does drug concentration matter in percutaneous absorption?

higher drug concentration leads to higher absorption because the more concentration you have the better the concentration gradient is for passive diffusion so you will have more absorption

how does area of application affect percutaneous absorption? does this effect the rate?

larger area you cover with product the more absorption you have. this effects the amount not the rate

what are other factors that are more human like that affect percutaneous absorption?

hydration of skin, site of application, occlusion, and individual variation

how do hydration of skin effect percutaneous absorption?

if the skin is hydrated it favors absorption of the drug because it will favor hydrophilic absorption

how does site of application effect percuteneous absorption?

apply in thin areas of skin because we want a thin stratum corneum

what do most transdermal drugs have that help with hydration?

they have occlusive moisture barrier to help keep the skin hydrated due to the hydration of the lipids near top layer of skin

what individual variations effect percutneaous absorption?

age and gender because skin changes with both

what are important factos for transdermal drugs?

they should be potent, have a short half life, and be non irritating to the skin

why are potent drugs and drugs with a short half life good transdermal drugs?

potent drugs are good candidates because you dont need to apply a patch so many times and because you can achieve constant delivert across the skin for a prolonged period of time

what is the goal daily dose of a drug for transdermal delivery?

less than 20 mg/day

what is the goal half life to make a drug a good transdermal drug?

8 to 10 hours or less

can every drug be delivered transdermally?

no they must meet certain criteria

what is the primary goal of transdermal patches?

maintain constant drug concentration at the skin surface

what are the 2 types of transdermal patches?

matrix and reservoir

what are the 3 components of a transdermal patch?

backing layer, drug layer, and adhesive layer

what does the backing layer of a transdermal patch do? why is this important?

it helps maintain skin moisture this is important because it helps with penetration of the drug

what does the drug layer do? what does it control?

it ensures that there is enough concentration gradient to achieve the required amount of drug to be penetrated over a period of time. it controls drug delivery rate 

what does the adhesive layer do?

helps stick the patch to the skin

can matrix trandermal patches be cut in half?

yes they can because they are a uniform mix of drug

can reservoir trandermal patches be cut?

no they can not because the drug is present in some sort of liquid or gel form so if you break it that reservoir/drug will come out

can microreservoirs be cut open?

yes because it is small beads dispersed so if you tampter with it not everything will come out

as the release rate of drug increases, does the patch size increase or decrease?

it increases

why is proper disposal of transdermal patches important?

it is important because there is a higher concentration of drug than the amount that is released therefore at the end of patch wear time there will be residual drug which can be harmful to pets or kids 

how do metered dose transdermal sprays work?

drug is dissolved in a solution then you apply one spray on the skin, drug is deposited on the skin and the volatile components evaporate, and a concentration of drug solution stays on the skin

is transdermal delivery fast or slow?

slow

what does transdermal absorption of a drug depend on?

concentration of drug in the patch, partition coefficient (log P), and diffusion coefficient

how can you change the concentration of drug in the vehicle to improve absorption of the drug?

by increasing formulation strength

how can you change the partition coefficient (log P: tells how water loving or lipid loving something is) to improve absorption?

by altering formulation chemistry

how can you change the diffusion coefficient in drug absorption?

alerting the skin chemistry through penetration enhancers

what are penetration enhancers? why are they useful?

increase the permeability of stratum corneum either in lipid region or through the cells. it decreases diffusion resistance so the drug can be absorbed better

what are the different groups of penetration enhancers?

chemicals, enzymatic, vesicular carriers, and physical techniques

what is a huge advanatage of transdermal drug delivery systems?

it allows effective use of drugs with short half life because you have constant delivery

why are transdermal patches not good for acute conditions?

this is because there is a lag time for the patch to start working