Modified Release Flashcards
What is Modified Release?
Products that alter the timing and/or rate of release of the drug substance
What is Extended Release (ER, XL, XR) Sustained Release (SR)?
A dosage form that allows at least a twofold reduction in dosage frequency
What is Delayed Release Timed Release (TR)?
A dosage form that releases a discrete portion(s) of a drug at a time other than promptly after administration
What is Orally disintegrating tablets (ODT)?
A dosage form designed to disintegrate rapidly in saliva after oral administration for rapid onset
What is Enteric coated (EC)?
A solid dosage form coated to prevent disintegration and dissolution in the stomach
What is the Rationale for development of a controlled release dosage form?
- 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
What is the order of release for modified release?
Zero - constant release
Which drugs are suitable for modified release (characteristics they need to have)?
- 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
Describe an osmotically controlled drug delivery system
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
What are the advantages of osmotically controlled oral drug delivery for controlled release:
- 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.
What are the ingredients of a tablet?
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)
How does an Ion-exchange products for controlled release?
- Insoluble cross-linked polymers are resins
- Drugs are attached to these resins and formulated into pharmaceutical products
- Within the GI tract the ions present displace the drug allowing drug to be released and subsequently absorbed
- Release of drug is controlled by diffusions of ions into the resin
How can you control release of ion exchange resins?
¥ 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
