1. MODIFIED RELEASE DOSAGE FORMby
A. S. Adebayo, PhD
Wednesday, April 19, 2017

2. Introduction
Modified release dosage forms are drug delivery systems (DDS) which, by virtue of formulation and product design, provide drug release in a modified form distinct from that of the conventional dosage forms. Drug release can either be delayed or extended in nature.
Wednesday, April 19, 2017

3. Delayed-release products
Usually enteric coated tablets or capsules designed to pass through the stomach unaltered to release their medication within the intestinal tract.
Wednesday, April 19, 2017

4. Extended-release products
Designed to release their medication in controlled manner, at pre-determined rate, duration and location in the body to achieve and maintain optimum therapeutic blood levels of drug.
Wednesday, April 19, 2017

5. Rationale for extended release pharmaceuticals
Drugs that are not inherently long lasting require multiple daily dosing to achieve the desired therapeutic effects.
Multiple daily dosing is often inconvenient and can result in missed doses, made-up doses and patient non-compliant with therapeutic regimen.
Blood levels of drugs from conventional immediate-release dosage forms taken more than once daily following definite schedule usually demonstrate sequential peaks and troughs (valleys) associated with each dose.
Wednesday, April 19, 2017

6. Rationale for extended release pharmaceuticals
Extended release tablets or capsules are commonly taken only once or twice daily compared with the conventional dosing of 2 to 4 times daily
Products are designed to provide an immediate release of drug which promptly produces the desired therapy, followed by gradual and continual release of additional amounts of drug to maintain this effect over a predetermined period of time.
The need for night dosing of drugs may be eliminated
Wednesday, April 19, 2017

7. Advantages of Extended-release Dosage Forms over Conventional Forms
Reduction in drug blood level fluctuations
Reduction in frequency of dosing
Enhanced patient compliance
Reduction in incidence of adverse side effects
Reduction in overall healthcare costs.
Wednesday, April 19, 2017

8. Terminology
The following terms have been applied to “extended” or “sustained” drug delivery systems:
Controlled-release
Extended release (ER)
Sustained-release (SR)
Timed-release (TR)
Long-acting (LA)
Prolonged-action (PA), and
Sustained-action (SA)
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9. Extended-release dosage forms
The US FDA defines ER dosage form as:
one that allows a reduction in dosing frequency to that presented by a conventional dosage form such as a solution or an immediate release dosage forms.
Wednesday, April 19, 2017

10. Delayed-release
These are dosage forms designed to release the drug at a time other than promptly after administration.
The delay may be time-based or based on the influence of environmental conditions such as g.i. pH, enzyme, pressure, etc
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11. Repeat action
These are dosage forms usually containing 2 single doses of medication, one for immediate and the second for delayed release e.g. bi-layered tablets.
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12. Targeted release
Drug release that is directed towards isolating or concentrating a drug in a body region, tissue, or site for absorption or drug action
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13. Extended-release Oral Dosage Forms
The general properties of drugs best suited for ER product design are:
They exhibit neither very slow nor very fast rates of absorption and excretion
They are uniformly absorbed from the g.i.t.
They are administered in relatively small doses.
They possess a good margin of safety i.e. Therapeutic Index (TI)
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14. Technology of ER Dosage Forms
ER Coated Beads, Granules or Microspheres –
Granules of drug may be coated with lipid materials such as beeswax, carnuba wax, glyceryl monostearate, cetyl alcohol, etc.
Careful blending of coated and un-coated granules and with coatings of different thicknesses will provide drug release of desired characteristics.
Wednesday, April 19, 2017

15. COMMERCIAL EXAMPLES Toprol-XL® (metoprolol succinate) tabs. (Astra);
Indocin SR ® (indomethacin capsules (Merck);
Compazine ® (prochloperazine) Spansule Capsules (SmithKline Beecham)
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16. Technology of ER Dosage Forms - Multitablet system
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17. Technology of ER Dosage Forms
Embedding drug in slowly eroding or hydrophilic matrix system – The design comprises of the drug substance plus excipient material that slowly erodes in body fluids thereby progressively releasing the drug for absorption
E.g. Quinidex® Quinine SO4 tablets (Robins); Oramorph ® SR Morphine SO4 tabs. Roxane ®
Wednesday, April 19, 2017

18. Technology of ER Dosage Forms: ER Microencapsulated Drug
–Microencapsulation is a process by which solids, liquid and semi-solid substances may be encapsulated into microscopic size particles through the formation of thin coating of “wall” material around the substance.
Different rate of drug release can be obtained by changing the core to wall ratio, the type of polymer coat and the method of microencapsulation.
E.g. K-Dur ®Microburst Release System (KCl) tabs. (Key)
Wednesday, April 19, 2017

19. Technology of ER Dosage Forms: Osmotic pump device
This consists of a core tablet surrounded by a semi-permeable membrane coating with a 0.4 mm diameter hole produced by laser beam.
The core tablet has 2 layers, one containing the drug (the “active” layer) and the other containing the polymeric osmotic agent (the “push” layer).
E.g. Glucotrol ® XL (glipizide) tablets (Pfizer)
Covera – HS ® (verapamil HCl) tabs. (Searle)
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20. Other methods
Embedding drug in an inert plastic matrix – e.g. Desoxyn® (methamphetamine HCl) tabs (Abbott); Procanbid ® (procainamide HCl tabs. (Parke-Davis)
Complex formation
Ion exchange resins
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21. Kinetics of Drug release
Drug release from conventional dosage forms, like the other processes of ADME, are governed by the first-order kinetics model.
In First-order model, drug release is dependent on the amount of drug available for release and therefore the rate of release declines exponentially with time.
Wednesday, April 19, 2017

22. Kinetics of Drug release…
Extended release dosage forms are governed by zero-order kinetics in which the rate of release is independent of amount of drug remaining in the dosage form.
Therefore a constant amount of drug will be released over time from extended release dosage forms
Wednesday, April 19, 2017

23. Assignments (Due Feb. 4, 2010)
Identify 3 controlled release formulation excipients, giving chemical and commercial names
What is the kinetic mechanism of drug release followed by Osmotic controlled delivery devices?
Using a suitable graph, illustrate the profile that would be observed in the following scenarios:
Burst release at peal plasma level
Design failure leading to “Dose dumping”
Design failure leading to drug being withheld
Wednesday, April 19, 2017

24. MODIFIED RELEASE DOSAGE FORM
THANK YOU FOR YOUR ATTENTION
Wednesday, April 19, 2017