Sustained Release and Prolonged Release Tablets and their Difference

In modern drug delivery the focus is not just on developing new molecules but on achieving maximum therapeutic benefits from the dose with minimum side effects. Controlled drug delivery systems such as Sustained Release (SR) and Prolonged Release (PR) tablets played a major role in this therapeutic evolution.

These two terms are often used interchangeably but there are important differences between them that influence formulation design, regulatory classification and clinical performance. This post explains principles, mechanisms, advantages and key differences between sustained release and prolonged release dosage forms.

Introduction to Modified Release Dosage Forms

Normal immediate release drug is released rapidly in body just after administration. This results in sudden increase of drug concentration in cell plasma which may cause side effects or require frequent dose.

Modified release dosage forms were developed to overcome these issues. These are designed to alter the drug release rate, time and location of release in the body. Modified release systems include:
1. Delayed Release (DR): Drug release occurs after a certain period of delay such as enteric coated tablets.
2. Extended Release (ER): Drug release is extended over a longer than normal dosage forms.
3. Sustained Release (SR): This maintains drug levels in the blood stream over a specific period of time.
4. Prolonged Release (PR): This extends the drug release to maintain therapeutic level for a longer duration than sustained release tablets.

Sustained and prolonged release both are subcategories of extended release systems but their purpose and release kinetics are different.

What are Sustained Release Tablets?

Sustained release tablets are the dosage forms where a drug is administered to a patient at a given or calculated rate. The aim of sustained release tablets is to maintain a certain concentration of the administered drug over a specific period of time in the patient's system while reducing possible side effects.

Mechanism of Sustained Release

Sustained release formulations use one or more of the following mechanisms.
A. Diffusion-controlled release: Drug release is controlled by diffusion through a polymer matrix or coating of the tablet.
B. Erosion-controlled release: Here drug release is controlled gradual erosion of matrix.
C. Osmotic-controlled systems: In this control system osmotic pressure is used to push the drug out through a small pore.
D. Ion exchange resins: In this system release of drug is controlled by changes in pH or ionic strength.

Key Characteristics

• Release drug at a required controlled rate.
• Maintains constant plasma concentration.
• Reduce dosing frequency from 3-4 times a day to 1-2 times.
• Prevents peaks and troughs that cause toxicity.

For example, Theophylline SR tablets are used for asthma management providing steady drug release for 12 to 24 hours.

What are Prolonged Release Tablets?

Prolonged release tablets are meant to affect after some time from the moment they are administered. They are known to be released in small portions over a long period of time with no specifications to time or rate of concentration.

Mechanism of Prolonged Release

Prolonged release tablets rely on any one of the following systems.
A. Polymer coatings: Polymer coatings slow down dissolution or diffusion of drug.
B. Matrix systems: Using this system tablet slowly disintegrate or dissolve.
C. Multi-particulate systems: Using this system drug can be released in pulses or continuously.

Key Characteristics

• Extends duration of drug action
• Doesn’t maintain uniform plasma levels
• Generally designed drugs with short half lives
• Useful in reducing the frequency of drug administration

For example, Diclofenac prolonged release tablets provide anti-inflammatory action for up to 24 hours reducing the need for multiple dodges daily.

Difference Between Sustained Release and Prolonged Release Tablets

1. Purpose: Sustained release tablets maintain a constant plasma concentration for a specific time while prolonged release tablets extend the duration of drug action beyond immediate release.

2. Release Rate: Sustained release tablet has a controlled and uniform release rate while prolonged release has gradual that may not be uniform.

3. Plasma Level: Sustained release tablets maintain concentration within the therapeutic window while in prolonged release it may fluctuate but remains within effective limits.

4. Mechanism: Sustained release tablets use controlled diffusion, erosion or osmotic release while prolonged release uses slow dissolution or disintegration.

5. Therapeutic Objective: A sustained release tablet has continuous therapeutic effect at a steady rate while prolonged release has a prolonged pharmacological effect, often for convenience.

6. Dosage Frequency: Sustained release tablets are administered once or twice daily while prolonged release tablets are required once daily or longer.

7. Suitable Drugs: Moderate to long half-life drugs are suitable for sustained release while short half-life drugs are suitable for prolonged release.

Advantages of Sustained and Prolonged Release Systems

For Patients

• Fewer doses per day make it suitable for patients.
• Reduced side effects due to stable plasma levels.
• More convenient for chronic therapies like diabetes and hypertension.

For Manufacturers

• Product differentiation and longer market life.
• Potential patent extension through formulation innovation.

For Healthcare Systems

• Better disease controller with fewer hospitalizations.
• Enhanced patient care leads to improved results.

Disadvantages and Challenges

Sustained release and prolonged release systems have numerous advantages but they also have some formulation and regulatory challenges.

A. Complex Manufacturing: Achieving consistent release of drug requires precise control of Polymer properties coating thickness and process parameters that takes time and investment.

B. Dose Dumping Risk: Any failure in drug release mechanism can result in the entire dose being released at once and it may cause toxicity to the patients.

C. Variable Absorption: There are variations in gastrointestinal motility, pH and food interactions in individuals that can affect release rate of the drug.

D. Cost: Development and testing of modified release formulations are more expensive than immediate release formulations because of their simplicity.

E. Regulatory Scrutiny: Regulatory agencies require detailed in vitro and in vivo correlation data for product approval and dissolution studies to prove consistent performance of the product.

Design Considerations

To develop a modified release system following points are required to understand.

• Physicochemical properties of the drug: It includes variability, stability and half-life of the drug.
• Therapeutic window: Understand whether it is narrow or wide.
• Absorption site: Define the part of body like upper intestine, colon, etc.
• Desired release duration: For how much time is drug release required like 8, 12 or 24 hours.

Common Technologies Used

1. Hydrophilic matrices: These are water-based (hydrophilic) polymers like HPMC or Xanthan gum.
2. Hydrophobic matrices: Hydrophilic materials include ethyl cellulose or waxes.
3. Coating systems: Coating systems using polymers such as you Eudragit or cellulose acetate.
4. Multiparticulate systems: In multiparticulate system pellets or microcapsules are encapsulated in a capsule or tablet.

Pharmacokinetic Profiles

The major difference between sustained and prolonged release tablets is in their plasma concentration and time profiles.

Sustained release tablets produce a flat curve after reaching the therapeutic concentration and maintain it steady for several hours.

Prolonged release tablets produce a gradual decline curve in concentration over time extending the duration of effect but not maintaining constant drug levels.

It is important to understand these pharmacokinetic profiles during formulation design and bioequivalence studies of the drug.

Applications of Sustained and Prolonged Release Formulations

These forms of tablets are ideal for chronic conditions that require long term therapy like hypertension, diabetes, pain management, asthma and psychiatric disorders. They reduce the burden of multiple dodging and improve quality of life of the patients using these formulations as treatments.

Frequently Asked Questions (FAQs) on Sustained and Prolonged Release Tablets

Q1: What are sustained-release tablets?

Answer: Sustained release tablets are also known as extended release tablets or controlled release tablets. These tablets have controlled release of the active component over an extended period of time. Due to this controlled and slow release allows a prolonged drug effect and also reduces the dose frequency.

Q2: What are prolonged release tablets?

Answer: Prolonged release tablets are very similar to sustained release tablets with a difference of not having the control on the concentration of drug in the body.

Q3: How do sustained-release tablets work?

Answer: Sustained release tablets work on various mechanisms that depends upon the type of formulation used. Generally, polymer binders and tablet coating are used to control the tablet drug release. These methods are used to ensure the consistent and controlled drug release.

Q4: What are the advantages of using sustained-release tablets?

Answer: Sustained release tablets have various advantages including reduced dose frequency, providing consistent drug concentration in the body, maintaining therapeutic level of drug and minimizing the dose concentration fluctuation in the body.

Q5: What factors are considered when formulating sustained release tablets?

Answer: Severy factors are considered during the formulation of sustained release tablets including pharmacokinetics of the drug, appropriate polymer compatibility of the drug with excipients and desired release profile of the tablet.

Q6: How are sustained release tablets evaluated for quality and performance?

Answer: Sustained release tablets undergo various tests to evaluate the performance and quality including drug release kinetics, dissolution profile, stability, content uniformity and physical parameters. Dissolution test is generally used to evaluate the drug release and consistency of the released drug from the tablet.

Q7: Can all drugs be formulated as sustained release tablets?

Answer: No, all drugs are not suitable for sustained release formulation. Certain drugs have narrow therapeutic index and require immediate release for optimal effect. Some drugs have specific release requirements that can not be achieved by the sustained release formulation. Each drug is required to evaluate individually to determine their suitability for sustained release formulation.

Q8: Are there any disadvantages or limitations to sustained release tablets?

Answer: Sustained release tablets have several advantages but these have some disadvantages including slower therapeutic effect in comparison with immediate release tablets and it has complex formulation and higher manufacturing cost. Additionally, all drugs can not be formulated as sustained release tablets.

Q9: Are sustained release tablets and extended-release tablets the same thing?

Answer: Yes, sustained release and extended release both terms are used for the controlled release tablets. These tablets release the active ingredients gradually for an extended period of time.