2: Polymers

a large molecule made up of many small repeating units

polymer

small molecule that combines with other molecules of the same OR different types to form a polymer

monomer

do all of the monomers of a polymer have to be identical ?

NO

H-(O-CH2-CH2-)n -OH

is polyethylene glycol (PEG) a monomer or polymer?

monomer

depending on how many units there are determines if it is a dimer, oligomer, or polymer

H-(OCH2-CH2-)₁₀₀ -OH

is the following a monomer, oligomer, or polymer

OLIGOMER because number of repeating units is between 30-100

if 200+ then polymer

What are polymers used for?

1. to develop devices for controlling ____ _______

2. for replacing failing natural _________

3. _________ delivery

4. transdermal patches use polymers as ________, adhesives, or drug _______________ in _______ or membrane products

1. drug delivery

2. organs

3. oral

4. backing, carriers in matrix

how can polymers be used in oral delivery?

1. coating

2. taste maskers

3. protective agents

4. releasing controlling agents

5. drug carriers

6. binders

metoclopramide is a capsule that uses polymers as a coating for a controlled/extended-release

controlled

Polymers are mixed into lactose pellets to control/extend their release in the body.

what does that mean?

extend

allows for small portions of the drug to come out at a time so they can remain effective for a longer period of time

how are polymers used in transdermal patches

• carries drug and controls how much of the active ingredient reaches the patient

• backings

• adhesive

can ALL polymers turn into glass or only certain ones?

ALL polymers can turn into glass

what allows a plastic polymer to turn to glass?

Glass Transition Temperature (Tg)

If the polymer experiences temperatures BELOW the Tg it will turn to glass

polymers above the Tg remain plastic

Do all polymers melt at a certain temperature Tm?

NO

some without Tm will burn instead of melting such as tires

What value will always appear of a differential scanning calorimeter for a polymer? Which value will only appear for certain polymers?

Tg - glass transition temperature ALWAYS

Tm - melting point SOMETIMES

Tg is an expression of _______ __________

and is an important factor for _______ dosage forms

molecular motion

SOLID

a chewable dosage form needs to be soft and flexible at mouth temperature at about ______ without MELTING or turning into GLASS

37 degrees Celsius

what are the two ways monomers come together?

1. addition

2. condensation

ADDITION METHOD OF POLYMERIZATION:

polymerization starts by the addition of a _____ ______ on the MONOMER which contains a _____ _______

free radical on MONOMER which contains DOUBLE BOND

does the addition or condensation method of polymer synthesis produce high molecular weight polymers?

addition

in order for the CONDENSATION method of polymerization to work

• monomers must contain ______ ________ such as ______, _______ ,or _______

• when the monomers react, what is the byproduct that escapes?

functional groups

hydroxyl, carboxyl, amines

WATER ESCAPE

does the addition or condensation method of polymer synthesis produce low molecular weight polymers?

condensation

Polymer _________ describes whether a polymer is

• linear

• branched

• cross-linked

determines the degree of freedom of polymer

which has the most restricted movement?

TOPOLOGY

most constricted = cross-linked

Does the following describe Linear or Crosslinked Polymers ?

• viscous

• soluble

• processable

linear polymers

does the following describe cross linked or linear polymers?

• higher transition temperature

• highly swellable

• Ridgid

• thermally stability

cross linked polymer

If a linear polymer is cross- linked it is

• less _____________

• more ____________

less soluble

more swellable

a cross-linked polymer can swell in a solvent to an extent that is ____________ related to the amount of cross-linkers

inverse

a cross-linked polymer is more likely to swell with less cross-linkers which makes it rigid but cross-linkers are more likely than linear polymers to swell as opposed to dissolve (lose solubility with increased ridgitity)

physical cross links are composed of which types of bonds?

• hydrostatic (hydrogen bonds)

• hydrophobic (vanderwalls)

• electrostatic (ionic)

what would happen if you added water to a physical cross-link

adding water would turn the polymer to swell into a gel and decompose

physical cross links are composed of which types of bonds?

ionic (electrostatic)

hydrogen (hydrostatic)

hydrophiboc (vanderwalls)

what happens when you add water to chemical cross-links? whats an example?

polymer will swell and expand but will not dissolve/degrade

ex. orbeez

polymer chains are in a ________ conformation at rest

they assume ______ conformation once they are loaded

coiled

extended

in the dissolution of a polymer and polymer swelling,

the load originates from the interaction of a polymer and a solvent as well as the ______ ________ of ions inside the polymer structure and the solution

concentration gradient

how do gels form form polymer chains originally in coiled conformations?

once you add water the coil of the polymer extends and the polymer makes new points of contact with itself creating a gel

depending on the nature of _____-_______, a hydrogel is classified as chemical or physical

cross-linking

Covalently cross-linked gels that DO NOT dissolve in water or other organic solvents unless the cross links are broken apart

NOT good for the release of biologics

chemical gels

________ bonding, _________ interaction, and ______ are the three major tools in preparing a physical gel

hydrogen

hydrophobic

complexation

are physical or chemical gels more often used?

what are two examples of physical gels?

methylcellulose

polyethylene glycol

when placed in excess _________, hydrogels such as ORAJEL are able to swell rapidly and retain large ________ of _______ in their structures

why is this useful?

water

retain large volumes of water

drug gets trapped in the polymer gel

hydrogels such as Orajel are usually hydrophobic/ hydrophilic

cross-linked by either _________ bonds or by other __________ forces such as ionic interaction, hydrogen bonds, hydrophobic interactions

• hydrophilic (can retain water)

• chemical or cohesion

___________ are polymers used in solid dosage forms to help drugs with disintegration

can speed up the disintegration process from hours to 30 seconds

superdisintegrants

what are two examples of superdisintegrants ?

Crospovidone and Croscarmelose

Allza’s Oros technology is based on an _________ concept providing 24 hour CONTROLLED/EXTENDED drug release that is independent of many factors such as diet status

OSMOTIC

Controlled

how does Oros work?

• osmotic core contains _____

• _____-______ ___________ allows water to enter and pill to swell

• ______ ______ is a hole in the tablet which allows the drug to be released based on the concentration of the active ingredient outside the tablet

• drug

• semi permeable membrane

• delivery orifice

what makes up the semipermeable membrane that selectively allows water to enter Oros and prevents responsiveness to any pH CONTROLLING its release

cellulose acetate

what is the difference between type A and type B osmotic tablets and pumps

type A has a solid osmotic core

Type B has a liquid osmotic core

both swell with water entering its permeable membrane and leave with the additional pressure through the delivery orifice

polymers in LIQUID dosage forms are generally used as

• ________ induced agents

• _________ stabilizers

• viscosity

• suspension

Cellulose ethers such as __________ or _________ are used in LIQUID oral or ophthalmic suspensions

Methyl Cellulose or Hydroxypropyl Methylcellulose

what are disadvantages of using natural gums such an guan or xanthum gum as liquid dosage stabilizers?

• since they are found in nature they is a lack of consistency within batches

• they allow for bacteria growth

Pharmaceutical polymers are widely used to achieve :

• taste masking

• controlled release

• enhanced stability

• improved bioavailability (prevent metabolism before reaching target)

what are the different types of controlled released?

• extended: drug released gradually to maintain levels in bloodstream for long periods of the time

• pulsatile: release drug periodically to mimic internal rhythms

• targeted: prevents the release of the drug until it reaches the targeted organ

what two polymers are NON bioderodable/degradable

poly-methyl-metha-crylate (PMMA)

ethylene vinyl acetate copolymer (EVA)

which polymers are biodegradable/erodable ?

1. polylactic acid (PLLA)

2. polylactic/ glycolic acid (PLGA )

3. polycaprolactone (PCL)

4. polyanhydride

nexplanon is involved in the controlled release of etonogestrel contraceptive

is nexplanon biodegradable?

NO

why is it better for a drug to be biodegradable?

if a drug is biodegradable then you don’t need to remove it from your system through surgery

ex. nexplanon is non biodegradable and must be removed surgically

• Glycolide

• Dl-Lactide

• e-Caprolactone

are the following monomers or polymers?

are they biodegradable or nonbiodegradable?

MONOMERS

BIODEGRADABLE

what are a few uses for biodegradable polymers?

• pin into broken bone will dissolve on its own, no need to surgically remove

• deep gum infections

• poly anhydrides are placed into brain and do not need to be surgically removed after

Poly Anhydrides such as

• Sebacic Acid (SA)

• bis(p-carboxyphenoxy)propane

are biodegradable/nonbiodegradable dime-sized wafers that deliver _______to the brain to kill surrounding tumor cells post-surgery

BIODEGRADABLE

BCNU

Gliadel Wafers are biodegradable ________ _________ used to kill surrounding tumor cells post tumor removal surgery

poly anhydrides

What are the three types of drug delivery systems associated with BIOERODIBLE polymers ?

1. Diffusion Controlled

2. Swelling Controlled

3. Chemically Controlled

what is the difference between the different types of controlled tablets

• diffusion

• swelling

• chemically

diffusion: high —> low until matrix biodegrading

swelling: water enters and releases drug from tablet

chemically: layers released overtime through EROSION

what are the two different types of diffusion controlled systems?

1. reservoir

2. matrix

what is the difference between the two diffusion controlled systems? (reservoir vs matrix)

matrix= extended release (mixed into drug)

reservoir= controlled release (coats drug)

How to make a matrix system:

1. crush drug and __________

2. add a ________ to the mixture

3. evaporate __________

4. ___________

what is an example?

1. polymer

2. solvent

3. solvent

4. compress

VOLTAREN

which system involves a polymer coating on top of the drug causing a certain amount of drug to be released each hour ?

what is an example?

reservoir system

ex. metoclopramide

which diffusion system

• polymer coating

• zero order (current concentration doesn’t determine how fast the drug is eliminated— same amount released every hour)

• CONTROLLED RELEASED

reservoir system

which diffusion system

• crushed and mixed with crushed drug

• first order (the amount of drug remaining influences how fast it is going to be eliminated)

• EXTENDED-RELEASE

matrix

is the matrix or reservoir system used for extended-release?

are they released in zero order or first order fashion?

matrix

first order (as time goes on it is released slower)

is the matrix or reservoir system used for controlled release?

are they released in zero order or first order fashion?

reservoir

zero order (same amount released every hour once you reach destination)