Pts.1-3 Modified- Release Dosage Forms- Mirza

Can two dosage forms be prescribed interchangeably?

• exam q???

no

Say we had carvedilol IR tablets and carvedilol CR capsules. What would these be referred to as?

pharmaceutical alternatives

What is controlled (modified) release?

• exam q

forms designed to alter and/or control the pattern of drug release in a certain way as compared to that of a conventional (IR) dosage form

What 3 THINGS do controlled release forms control?

• exam q

1. timing of drug release

2. rate of drug release

3. location of drug release

Think: timing, rate, location

What are some types of controlled (modified) release oral dosage forms?

• FYI

• extended-release

• delayed-release

• targeted-release

• orally disintegrating tablets

What is the difference between extended and delayed release DFs?

• exam question!!!!!!!!!!!!!!

extended- DF that allows at least a twofold reduction in dosage frequency compared to IR DF

• ex: Coreg CR

delayed- release a discrete portion of drug at a time other than promptly after administration

• ex: enteric coated tables

BASICALLY: extended releases drug more slowly, delayed releases the product shortly after administering like going to another organ, then releasing

What are the advantages of controlled/modified release dosage forms?

• exam question

• avoid fluctuations (shifting) in drug blood levels

• reduced dosing frequency

• more convenient and more pt. compliance

• reduce ADRs

• cost effective for pt

What are the typical ROAs for controlled/modified release products?

• “memorize”-mirza

• oral (most common)

• parenteral

• transdermal

• ocular

• subdermal

• vaginal

• implants

What do each of the following abbreviations mean?

• “memorize”-mirza

CD	Controlled dose
CR
CRT
LA
SA
SR
TD
TR
XL
XR
PA

CD	Controlled dose
CR	controlled release
CRT	controlled release tablet
LA	long acting
SA	sustained action
SR	sustained release
TD	time delay
TR	timed release
XL	extended release
XR	extended release
PA	prolonged action

True or False: Extended-release dosage form must provide at least threefold reduction in dosage frequency as compared to conventional dosage form.

• exam q

false- it’s twofold

What are the materials used in enteric coating?

• “memorize”-mirza

• cellulose acetate phthalate- most common

• shellac

• fats

• fatty acids

Consider the following delayed-release tablet formulation:

Carvedilol, carnauba wax, cellulose acetate phthalate, and SDS. Which of the ingredients in the formulation renders the solubility of this dosage form in the intestine?

cellulose acetate phthalate- (material in delayed release coating)

How does the PK Profiles of Conventional Dosage forms compared to controlled/modified release dosage forms?

• FYI

What is the reaction order of controlled/modified release?

zero-order

For an ideal ER dosage form there are 2 portions. The one that provides the ____________ priming dose and the one that provides the _________________ or sustained dose.

provides the initial priming dose and the one that provides the maintenance or sustained dose.

What are some characteristics of ER formulations?

• exam q on this topic

• used for chronic conditions

• WIDE therapeutic index

• half life between 2-6 hrs

• pretty soluble

• avg absorption rate

To create extended-release formulations, what technologies are used?

• FYI

• coated particulate systems

• microencapsulation

• matrix systems

• complex formulations

• ion Exhange resins

• osmotic pumps

How do coated particulates work?

basically a “coated” bead

• the core is a sugar/starch bead and that is coated in a drug/API layer

• the drug layer is then coated with polymers like beeswax or cellulose

How does microencapsulation work?

basically solids, liquids, or gas are enclosed in particles to form a thin coating around it

• like a hershey’s almond bar

What are the encapsulating materials that are used in microencapsulation?

• EXAM Q

• gelatin

• synthetic polymers (PVA, ethylcellulose, PVC)

WHAT IS THE MOST IMPORTANT POLYMER!!!!?????

• I just know the answer to an exam question is going to be this. (don’t know how he’s gonna ask it tho)

HPMC (hydroxypropyl methylcellulose)

How do matrix systems work?

basically drug is mixed(dispersed) w/ an excipient (usually HPMC) that is nonabsorbable from the GIT but slowly dissolves in the body fluids, releasing the drug

What is the difference between encapsulation and matrix systems?

encapsulate- drug COVERED in polymer

matrix- drug is DISPERED in polymer

To make a tablet in a matrix system you need high compression forces, the fact you have to compress so hard will influence properties like…

porosity and tortuosity

Porosity is ___________ related to compressional forces.

• EXAM Q on porosity and tortuosity

inversely

The higher the compressional forces, the _______________ the porosity.

• EXAM Q on porosity and tortuosity

lower

Tortuosity is not directly proportional to the compressional forces, but an increase in compressional forces, ______________ tortuosity.

• EXAM Q on porosity and tortuosity

increase compression= increase tortuosity

What is porosity and tortuosity?

porosity- void (empty) space in a powder or matrix

tortuosity- the tortuous or zig-zag path the drug takes to get out of the matrix

What are ion-exhange resins and their advantage?

basically drugs are passed through ion-exchange column to form insoluble nonabsorbable resin-drug

• advantage: masks bad tasting drugs!

What is an osmotic pump system?

• EXAM Q (i just stuck my whole slide in bc idk how he’s gonna ask)

• AKA GITS (gastrointestinal therapeutic system)

• drug is formulated as a tablet DF coated with a semi-permeable or impermeable membrane

What reaction order is osmotic pump system?

• EXAM Q

zero

What does “OROS” stand for?

• exam Q

Osmotic Release Oral System

Complex formulations are pH _______________, osmotic pump systems are pH _________________.

(independent or dependent)

dependent, independent

Disadvantages of extended-release DF:

• “dose dumping”

• lack of flexibility

• limitations for HIGH dosage

• cost of development

What is a patient counseling point for modified released tablets?

do NOT crush or chew!!! (destroys all the systems we just talked about)