Sustained release (SR) tablets are oral dosage forms designed to release a drug slowly over an extended period, usually 8 to 24 hours, so that it can be taken once or twice a day instead of three or four times. By keeping blood levels of the drug steadier, they can improve patient compliance and reduce side effects linked to high peak levels.
What Are Sustained Release Tablets?
A conventional (immediate release) tablet releases its whole dose within about an hour. Blood levels rise to a peak and then fall, so another dose is needed after a few hours. A sustained release tablet slows down the release of the drug, so absorption continues for many hours and the drug level stays within the therapeutic range for longer.
The terms sustained release, controlled release, extended release and prolonged release are often used interchangeably, but they have slightly different meanings:
Sustained, controlled, extended and delayed release: the differences
| Type | How the drug is released | Main purpose | Example |
|---|---|---|---|
| Immediate release | Quickly, usually within 30–60 minutes | Fast onset of action | Paracetamol tablets |
| Sustained release (SR) | Slowly over many hours; the rate is not necessarily constant | Fewer doses a day | Diclofenac SR tablets |
| Controlled release (CR) | At a predetermined, often nearly constant (zero-order) rate | Very steady blood levels | Nifedipine osmotic tablets |
| Extended release (ER, XR, XL) | Umbrella term used by the USP that covers both SR and CR | Once- or twice-daily dosing | Metformin XR tablets |
| Delayed release | Release starts only after the tablet leaves the stomach | Protect the drug from acid, or the stomach from the drug | Pantoprazole enteric-coated tablets |
In Europe, the term "prolonged-release" is used for products that most other markets call extended release.
Figure: Optical pictures taken at various points throughout the dissolution experiment of whole and cut sustained release matrix tablets. 2019 (Maira T, et al. 2019).
Ideal Properties of a Drug for Sustained Release
Not every drug is suitable for a sustained release tablet. Good candidates usually have:
- A half-life of about 2 to 8 hours. Drugs with very short half-lives would need impractically large doses in one tablet. Drugs with long half-lives already last long enough without modification.
- A moderate dose. Very large single doses make the tablet too big to swallow.
- Good absorption throughout the gastrointestinal tract. Drugs absorbed only in a small region of the upper intestine may pass that region before they are released.
- Adequate solubility and stability in gastrointestinal fluids.
- A reasonably wide therapeutic index. If a narrow-therapeutic-index drug is released too quickly (dose dumping), the result can be toxic.
Formulation Methods for Sustained Release Tablets
Matrix systems
The drug is mixed throughout a polymer that controls its release. In hydrophilic matrices, polymers such as hydroxypropyl methylcellulose (HPMC) swell into a gel layer when wetted; the drug diffuses through the gel while the matrix slowly erodes. Hydrophobic or inert matrices use waxes or insoluble polymers such as ethylcellulose. Matrix tablets are the most common type, because they can be made by direct compression or granulation with standard equipment.
Reservoir (coated) systems
A drug core is coated with a rate-controlling membrane, for example ethylcellulose or ammonio methacrylate copolymers (Eudragit RS/RL). The drug diffuses slowly through the coating. If the coating is cracked, the entire dose can be released at once.
Osmotic pump systems
The tablet has a semi-permeable coating with a laser-drilled opening. Water enters the tablet by osmosis and pushes the drug out through the hole at a nearly constant (zero-order) rate. Examples include osmotic forms of nifedipine and methylphenidate. The empty shell may appear in the stool, which is normal.
Multiparticulate systems
The dose is divided into many small coated pellets or beads, filled into capsules or compressed into tablets. They spread more evenly through the gut and carry a lower risk of dose dumping than a single coated unit.
Ion-exchange resin systems
The drug is bound to an ion-exchange resin and released as it exchanges with ions in gastrointestinal fluids. This approach is used mainly in liquid sustained release products, such as dextromethorphan polistirex suspension.
Uses and Examples of Sustained Release Tablets
Sustained release products are used mainly for long-term conditions where steady drug levels and simple once- or twice-daily dosing matter:
- Hypertension and angina: nifedipine, metoprolol succinate, isosorbide mononitrate
- Type 2 diabetes: metformin extended release, glipizide extended release
- Pain and inflammation: diclofenac SR, tramadol SR
- Asthma: theophylline SR
- Epilepsy: sodium valproate and carbamazepine controlled release
- Parkinson’s disease: levodopa–carbidopa controlled release
- ADHD: methylphenidate extended release
Advantages of Sustained Release Tablets
- Fewer doses per day, which improves patient compliance
- Steadier blood levels, with smaller peaks and troughs
- Fewer peak-related side effects for drugs whose side effects depend on high peak levels
- Better control of symptoms at night, for example in asthma or pain, without waking up for a dose
- More convenient long-term therapy for chronic conditions
Disadvantages of Sustained Release Tablets
- Risk of dose dumping if the tablet is crushed, chewed or (for some products) taken with alcohol
- Less flexibility to adjust the dose, because tablets usually cannot be split
- Delayed onset of action, so they are unsuitable when a rapid effect is needed
- Effects last longer if the drug must be stopped, for example after an adverse reaction
- Possible lower bioavailability if the drug is not fully released before the tablet leaves the absorption site
- More complex development and higher cost than conventional tablets
Patient Counselling Points
- Swallow the tablet whole. Do not crush, chew or break it unless the label says it can be split.
- Take it at the same time each day.
- Check the label or ask the pharmacist about alcohol, because some products can release their dose too quickly with alcohol.
- If a tablet shell appears in the stool, the drug has still been released and absorbed.
- If a dose is missed, follow the leaflet or ask a pharmacist rather than doubling the next dose.
Quality Control of Sustained Release Tablets
The key QC test is dissolution at several time points (for example at 1, 4 and 8 hours or more) to confirm the drug is released at the intended rate. Unlike an immediate release tablet, which needs only one time point, an SR tablet must release neither too slowly nor too quickly at every stage. A change in polymer grade, hardness or coating thickness can shift the release profile, which is why these are critical quality attributes.
Frequently Asked Questions
What are sustained release tablets?
Sustained release (SR) tablets release their drug slowly over an extended period, usually 8 to 24 hours. This keeps blood levels steadier and allows the medicine to be taken once or twice a day instead of three or four times.
What is the difference between sustained release and controlled release?
Sustained release tablets release the drug slowly, but the rate can change over time. Controlled release tablets release the drug at a predetermined, often nearly constant rate, giving steadier blood levels. In practice, the terms are often used loosely.
What do SR, ER, XR, XL and CR mean on medicine labels?
They all indicate modified release: SR is sustained release, ER, XR and XL are all used for extended release, and CR is controlled release. They tell the patient that the tablet releases its drug slowly and should usually be swallowed whole.
Can sustained release tablets be crushed or chewed?
No, unless the label specifically allows it. Crushing or chewing destroys the release mechanism and can release the whole dose at once, a problem called dose dumping, which may cause side effects or toxicity.
What is dose dumping?
Dose dumping is the rapid release of a large part of the drug from a modified release dosage form. It can happen if the tablet is crushed or chewed, or with some formulations if they are taken with alcohol.
Which drugs are suitable for sustained release tablets?
Good candidates usually have a half-life of about 2 to 8 hours, a moderate dose, good absorption throughout the gastrointestinal tract and adequate stability. Drugs with very long half-lives or very large doses are poor candidates.
Why do some extended release tablets appear in the stool?
Some formulations, such as osmotic pump tablets, have an outer shell that does not dissolve. The drug is released through a tiny hole and the empty shell passes out in the stool. This is expected and does not mean the drug was not absorbed.
How are sustained release pellets coated?
Multiparticulate pellets are usually coated with a rate-controlling polymer in a fluid bed coater. Learn how the equipment works in our guide to the fluidised bed dryer.
How does sustained release change the dosing schedule?
Because the drug is released slowly, a sustained release product is usually given once or twice a day, while the same drug as an immediate release tablet may need three or four doses. Read more about dose and dosing frequency in our guide to posology.
