Modified Release

Question 1

What is Modified Release?

Answer 1

Products that alter the timing and/or rate of release of the drug substance

Question 2

What is Extended Release (ER, XL, XR)
Sustained Release (SR)?

Answer 2

A dosage form that allows at least a twofold reduction in dosage frequency

Question 3

What is Delayed Release
Timed Release (TR)?

Answer 3

A dosage form that releases a discrete portion(s) of a drug at a time other than promptly after administration

Question 4

What is Orally disintegrating tablets (ODT)?

Answer 4

A dosage form designed to disintegrate rapidly in saliva after oral administration for rapid onset

Question 5

What is Enteric coated (EC)?

Answer 5

A solid dosage form coated to prevent disintegration and dissolution in the stomach

Question 6

What is the Rationale for development of a controlled release dosage form?

Answer 6

• Increases drug efficacy by maintaining constant plasma level in the therapeutic window
• Reduces dosing frequency and eliminates drug accumulation in the body
• Increases patient compliance
• Can reduce the cost of effective therapy

Question 7

What is the order of release for modified release?

Answer 7

Zero - constant release

Question 8

Which drugs are suitable for modified release (characteristics they need to have)?

Answer 8

• Dose <500mg as the dosage form may become too large
• Good stability along the entire GI tract (pH stable)
• Aqueous solubility >0.01mg/mL
• LogP value between 1-3
• Absorption rate >0.17 h-1
• An absorption rate of 0.17h-1 results in >80% absorption
• Elimination half-life between 2-8 hours

Question 9

Describe an osmotically controlled drug delivery system

Answer 9

Osmotic core (salty) 
Membrane lets water in but not out
Water moves into core (to low water potential) then forces drug out

• Core = drug alone or together with an osmotic agent
• The osmotic agent pulls in water from the GI fluid to form a saturated solution inside the device
• Also increased pressure in the device
• Saturated drug solution leaves the device for subsequent absorption
• Shell = semipermeable polymer membrane with an orifice for delivery of drug
• Examples of semi-permeable polymers: cellulose acetate, ethylcellulose, polyurethane, polyvinyl chloride, polyvinyl alcohol

Question 10

What are the advantages of osmotically controlled oral drug delivery for controlled release:

Answer 10

• Zero-order kinetic release is achievable.
• The drug is delivered at a constant rate that is independent of time and drug concentration.
• Drug release is independent of physiological factors of the gastrointestinal tract, including gastric pH and hydrodynamic conditions.
• Drug release is generally not affected by the presence of food.
• The release rate can be programmed by modulating release-control parameters.
• Delivery may be delayed or pulsed if desired.
• Soluble and insoluble compounds can be delivered.
• Production scale-up is easy.

Question 11

What are the ingredients of a tablet?

Answer 11

Tablet Core
¥	Polyethylene oxide
¥	Hypromellose (5 cp)
¥	Magnesium stearate
¥	Sodium chloride
¥	Ferric oxide, red (E172)

Coating
¥	Cellulose acetate
¥	Macrogol (3350)
¥	Hydroxypropylcellulose
¥	Hypromellose (3 cp)
¥	Propylene glycol
¥	Hypromellose (5 cp)
¥	Titanium dioxide (E171)
¥	Ferric oxide, red (E172)

Polish and Print
¥ Black ink for printing Opacode S-1-17823
¥ (Contains: iron oxide black (E172) and Shellac)

Question 12

How does an Ion-exchange products for controlled release?

Answer 12

1. Insoluble cross-linked polymers are resins
2. Drugs are attached to these resins and formulated into pharmaceutical products
3. Within the GI tract the ions present displace the drug allowing drug to be released and subsequently absorbed
4. Release of drug is controlled by diffusions of ions into the resin

Question 13

How can you control release of ion exchange resins?

Answer 13

¥ Diameter of resin beads
¥ Degree of crosslinking within the resin
¥ pKa of the ionisable resin group
¥ Electrolyte concentration in the microenvironment
Coatings often applied to final product to also control release