Can modified release drugs boost patient compliance?
Drug delivery systems offering modified release have grown significantly in popularity in the pharmaceutical sector in recent years.
These products have been designed to control the rate and/or the site of release of their active pharmaceutical ingredient (API) to achieve clinical objectives far beyond what could be done with conventional drugs, including improved efficacy and reduced pressure on patients to follow a complex administration regime.
The potential of modified release drugs
This innovative new generation of drugs offers key benefits from a therapeutic perspective, which could be summarised as extended release and delayed release.
The key advantages of modified release formulations include:
- Protecting acid-sensitive drugs
Modified release product features, such as an enteric coating, can delay release of acid-sensitive drugs until they have moved through the gastro-intestinal tract, also known as the first pass liver, enhancing their efficacy and minimising the risk of adverse effects, such as stomach irritation.
- Sustained blood concentration
Modified release products designed to extend release can be ideal for drugs with a sub-optimal half-life, as they can sustain therapeutic blood level concentrations over longer periods, without the need for additional doses throughout the day.
- Fewer adverse side effects
The controlled release offered by modified release can prevent the post-administration high-peak blood concentrations that are typically seen when using conventional drugs. By regulating the release of the API, adverse side effects become less intense.
- Greater patient useability
In order to maintain therapeutic blood concentration, it is often the case that drugs with short half-lives need to be taken multiple times during the course of the day. By reducing the number of daily doses, delayed release modified release products can be easier for patients to use without missing doses, enhancing compliance.
The pros of modified release pellet technology
It is possible to split modified release drug dosage forms in monolithic and multiple-unit formulations. The former is easy and straightforward to manufacture with conventional tableting procedures.
However, multiple unit preparations, such as pellets, are more complicated to produce. Nevertheless, they have considerable advantages from both a therapeutic and a manufacturing perspective.
For instance, they offer less variable progression in the digestive system, and can be used to combine components with drugs with different release profiles. When housed in a capsule, pellets can allow the modification of a dose without the need for reformulation – simply adjust the mass of pellets to change the dosage.
Pellet materials are also incredibly diverse. This means they can be filled into capsules or sachets, compressed into tablets, or even dispersed in a liquid suspension, catering to the varying administration needs of patients.
Exploring fixed-dose combinations
Modified release drugs offer another crucial benefit – they can be used to combine two or more drug products in a single carrier (i.e., capsules) to obtain a fixed-dose combination (FDC). This option is ideal for a patient population for whom treatment with a particular combination of APIs in a fixed ratio of doses has been shown to be safe, effective, and contribute to the overall therapeutic effect.
For instance, they are being increasingly used in the management of HIV/AIDS, malaria, and tuberculosis – some of the foremost infectious disease threats in the world today. By reducing the number of doses required each day, they are easier to administer, helping to boost patient compliance.
From a manufacturing perspective, it is easy to combine several types of pellets in a single FDC dosage form. Such combinations can lower the cost of manufacturing significantly compared to the cost of producing separate products to be administered concurrently. It also lowers packaging and logistics costs, helping to make them a much more efficient alternative to conventional dosage forms.
Barriers to development
While the benefits of modified release formulations are clear, there are challenges that need to be overcome when developing them.
Not only are the formulations themselves complicated to develop, but the manufacturing process for the dosage form is also often complex, and will require specialised production lines. Moreover, they need dedicated regulatory knowledge to ensure compliance.
Due to the relative youth of the drug type, many companies lack the in-house expertise to justify an investment in modified release. However, with the right expert support, they can successfully develop their first modified release formulation. In doing so, they can be confident they are at the forefront of drug development, creating products that are more effective and truly enhance the lives of patients.
To find out more about the development of modified release drug products, read this PharmTech article, Modified-Release Formulations: Improving Efficacy and Patient Compliance.