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What Does the Future Hold for Delayed Release Empty Hard Capsules?

An Exploration of Enteric Release Capsules in the Nutraceutical and Pharmaceutical Markets

The term “delayed-release” formulation refers to finished dosage form tablets or capsules, which are acid-resistant and protect the release of a medicament until the capsule has passed through the stomach into the small intestine.

Generally, in the case of capsules, either the final formulation is coated, or it is filled with pellets coated with acid-resistant polymers. Alternatively, the contents (powder, granules, or pellets), are filled into an empty hard capsule shell specially designed to demonstrate delayed release behavior. The industry is equipped with – and has already developed products using – these two approaches. However, there remains an expectation on the healthcare industry to receive “ready-to-fill” delayed release empty hard capsule shells to help support operational convenience and reduce the processing time required for coating.

As a result of this demand, the capsule manufacturing fraternity has been proactive when it comes to developing such functional capsules to support the industry’s development pipeline. In recent years, the discussion around these functional acidresistant capsules has also moved across into the pharmaceutical and nutraceutical industries. This has been illustrated with the launch of these capsules with further evolving technologies which provide better acid protection and have also been made available for pharmaceutical applications. As a result of this evolution, a variety of market intelligence predictions indicate a strong growth potential for these enteric release capsules from 2023–2030.

Unfortunately, despite the need for one, there is no pharmacopeial test method available to qualify a “ready- to-fill” delayed release empty hard capsule. This is undoubtedly due to the absence of any marketed pharmaceutical product using such capsules. However, given the industry demand for these capsules it is worth creating all possible control parameters to support their initial development. This should include all test methods, to ensure a current quality product, which is capable of being commercialised in the future. In the meantime, as an interim arrangement, the industry has adopted the pharmacopeial method of delayed release finished formulation.

Accordingly, the delayed release empty hard capsules should withstand a one-hour disintegration test in 0.1N HCL while the end formulation (filled capsules) must protect the inner content for at least two hours in 0.1N HCL (<10% drug release), followed by >75% release in 6.8 pH buffer within 45 mins unless otherwise specified in a dissolution study.

For further clarity, the delayed release capsules could be classified into “enteric capsules” and “modified release capsules”. Enteric capsules, also called gastro-resistant capsules, are capsule shells coated with a special polymeric film that acts as a barrier to the acidic environment of the stomach. Thus, allowing the intact capsules to be carried forward, released, and absorbed in the alkaline environment of the small intestine.