In the evolving landscape of pharmaceutical development, modified release (MR) tablets have emerged as a cornerstone technology for improving therapeutic outcomes and patient compliance. Unlike immediate-release formulations, MR tablets are designed to control the rate, timing, and location of drug release within the gastrointestinal tract for either prolonged or optimal drug delivery. This capability offers significant advantages, including sustained plasma concentrations, reduced dosing frequency, and minimised side effects. However, achieving these benefits requires a strategic approach to formulation design and manufacturing.

In this article, we’ll explore the key strategies for optimising drug delivery through modified release tablets, the challenges developers face, and the technologies shaping the future of MR formulations.

Why Modified Release Matters

Traditional immediate-release tablets deliver the active pharmaceutical ingredient (API) rapidly after ingestion, often resulting in peaks and troughs in plasma drug levels. These fluctuations can lead to:

• Reduced efficacy during trough periods.
• Increased risk of side effects during peak concentrations.
• Enhanced therapeutic effectiveness.
• Targeted release.
• Poor patient adherence due to frequent dosing schedules.

Modified release systems address these issues by maintaining therapeutic levels over an extended period, reducing dosing frequency, and improving overall patient experience. They can also allow for less frequent dosing, resulting in higher levels of patient adherence, and fewer side effects caused by the reduction of peaks and troughs in blood levels. For chronic conditions such as hypertension, diabetes, or pain management, MR tablets can transform treatment outcomes.  Certain MR strategies can also be used where targeted drug release is critical, such delivery to a specific area of the GI tract (e.g Colon) where the drug is absorbed.

Core Strategies for Modified Release Formulation

Designing an effective MR tablet involves balancing drug properties, excipient functionality, and manufacturing processes. Here are some of the primary strategies:

1. Matrix Tablets

Matrix tablets incorporate the API within a polymer network that controls drug release through diffusion and erosion. Common approaches include:

• Hydrophilic matrices (e.g., hydroxypropyl methylcellulose): Swell upon contact with gastrointestinal fluids, forming a gel layer that slows drug diffusion.
• Hydrophobic matrices (e.g., ethylcellulose): Resist water penetration, providing a more prolonged release profile.

2. Coating Technologies

Film coatings can be applied to tablets or pellets to modulate drug release. Techniques include:

• Enteric coatings: Prevent drug release in the stomach, targeting the intestine for absorption.
• Controlled-release coatings: Use polymers like Eudragit® to achieve sustained or delayed release.

3. Osmotic Systems

Osmotic-controlled release tablets use a semi-permeable membrane and osmotic pressure to deliver the drug at a near-constant rate, independent of gastrointestinal conditions. When the tablet enters the GI tract, water permeates through the membrane, dissolving the drug inside the core. The resulting solution is then pushed out through a laser-drilled orifice, driven by osmotic pressure. This mechanism ensures a predictable and sustained release profile, reducing variability caused by food intake or pH changes. Osmotic systems are particularly valuable for drugs requiring steady plasma levels, though they involve complex design and higher manufacturing costs compared to conventional approaches.

4. Multi-Particulate Formulations

Instead of a single tablet, multi-particulate formulations allow for the delivery of multiple APIs with different dissolution profiles. This simplifies release rates, and facilitates adjustments to pharmacokinetic and clinical performance. Multi-particulate can be particularly beneficial for alleviating side effects through the reduction of the effect of food on absorption.

Critical Considerations for Success

Optimising MR tablets requires attention to several factors:

The characteristics of the API are particularly important. Especially pertinent information includes:

• Solubility: The solubility of the drug must be considered to ensure that the drug is released in the correct area. For example, the pH of tablets must be carefully monitored to ensure the API is released in either the GI tract or the stomach. Some drugs which would optimally release in the upper GI are soluble at low pH, and will therefore need an enteric coating to ensure it is not released prematurely in the stomach. Meanwhile drugs that optimally release in the stomach would benefit from film coating.
• Permeability: The permeability of MR tablets is important in governing the ability of drug substances to transport across gastrointestinal membrane
• Half life: Ideally drugs with a half-life of 2-8 hours are best for MR dosage forms.  A shorter half-life requires large doses and longer half-life drugs will not benefit from or need MR.
• Dose size: High dose drugs will result in large tablets that are too large or uncomfortable to swallow.
• Stability: The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light. For modified release tablets, in which less frequent dosing is common, stability is paramount.
• Absorption window: Drugs absorbed only in the upper small intestine may be unsuitable because MR formulations may push drug release beyond this region.
• First‑pass metabolism MR:  systems that smooth plasma levels can reduce metabolic overload.
• Therapeutic index: Narrow therapeutic index drugs require tightly controlled release to avoid toxicity.
• Patient Needs: Patient adherence, and considerations around side effects are particularly important for ensuring successful patient adherence. Therefore, Dosing frequency, ease of swallowing, and tolerability must influence formulation design.
• Dose Dumping Risk: Formulations must avoid rapid, unintended drug release caused by factors such as, alcohol consumption, breakage or polymer failure.

“Modified release isn’t simply about making tablets that last longer; it’s about therapies that fit patients’ lives and medical needs.” At Upperton we combine a team of experienced scientists with world class GMP facilities and equipment to develop a wide range of modified release dosage forms. Our goal is simple: control release so patients don’t have to control their day.” – Dr Ian Lafferty.

Conclusion

Modified release tablets are powerful for enhancing drug delivery, improving patient adherence, and maximising therapeutic outcomes. By leveraging specifically selected modified release formulations, pharmaceutical developers can tailor release profiles to meet clinical needs. As technology continues to evolve, the potential for modified release in drug delivery will continue to improve patient experiences and outcomes.