Subscribe to Newsletter
Discovery & Development Drug Delivery, Ingredients, Formulation, Small Molecules

Why Encapsulation Is (or Should Be) King

It has been said many times that the shape of capsules makes them easier to swallow than tablets – and there are others in the industry that maintain the opposite. I’ve not hidden my affiliation above, so you can probably guess where my allegiance lies! Oral dosage forms come in all shapes and sizes. Whether a capsule, liquid, powder, pellet or tablet – each has a role in drug delivery. But what if we could combine two forms into one? Instead of re-treading the old ground of which dosage from is better, I’d like to focus on discussing why encapsulation is perhaps more future proof than tablets. One of the key benefits of capsules is the ability for liquid fill – and this technology lends itself to some important trends in APIs.

Firstly, although solid dosage forms are generally well received by patients, many new chemical entities are relatively insoluble in aqueous media, resulting in slow and incomplete dissolution in the intestinal milieu. Liquid formulations of drugs – either in solution or suspension – help address solubility issues, but are not always convenient to take. Liquid-filled capsules, in my view, offer the best of both worlds. And the very reason I started working with liquid-filled capsules was because I firmly believe that the advantages of the technology hadn’t been fully exploited. A liquid formulation designed for encapsulation retains the convenience and simplicity of oral solid dosage form delivery. Many compounds in the pipeline today exhibit poor solubility and require bioavailability-enhancing technology. In many cases, lipid-based formulations can significantly improve the solubility of an API – and dispersions or suspensions of drugs in lipidic vehicles or solvent and co-solvent approaches can be readily encapsulated into either capsules or soft gels.

Secondly, I believe that liquid formulations are also well suited to meet the formulation and safe handling challenges of high-potency APIs (HPAPIs), which make up an increasing proportion of industry pipelines. High potency drugs enable therapeutic efficacy at low concentrations. But while that may be clinically advantageous, they also complicate drug development and manufacturing processes. The required dose of a HPAPI is very low – sometimes less than a milligram – and it can be a challenge to achieve dose homogeneity. Ensuring uniform HPAPI content in each tablet, for example, requires careful selection of appropriate excipients, rigorous mixing studies at each scale of manufacture, and monitoring for powder de-segregation, which could translate to significant dose-to-dose variability. In some cases, companies have had to cease manufacturing particular products because they just couldn’t achieve dose reproducibility. Protecting operator safety is another key issue at all stages of product development and in my view, liquid fill technology minimizes the potential for operator exposure compared with the handling of solid active ingredients.

An example of a low-dose product with potency and bioequivalence issues that liquid formulation helped to address is levothyroxine. Levothyroxine was the subject of a review by the UK’s MHRA in 2013, which concluded that levothyroxine tablets were difficult to manufacture. As a result of the potential sensitivity of levothyroxine products to minor changes in processing technology, the manufacture of levothyroxine products should be considered “non-standard” despite using conventional blending, granulation and compression technology. And here is where a liquid filled capsule has a chance to shine. Liquid-filled capsules can accommodate low doses with good dose-to-dose reproducibility, as the drug, once in solution (or well-formulated suspension), is homogeneous, with no opportunity for de-segregation during capsule filling or product storage. The levothyroxine example offers an excellent case study in which liquid-filled hard capsule technology was shown to be capable of generating formulations of this drug with good dose reproducibility, hence avoiding the pitfalls associated with levothyroxine tablets.

I am sure it’s clear that I’m passionate about the potential of liquid-filled hard capsule technologies, but they are just one of many dosage forms that can help deliver ingredients to the body in the best way. In fact, there are some instances where tablets, pellets, liquids or powders may trump a capsule. Drug development, however, is becoming more complex and I think it is well worth the industry looking to advanced technologies. In particular, it’s important to choose the solution that best suits the characteristics of the API, meets the target product profile, helps ensure operator safety, and ultimately provides the best therapeutic outcome for patients.

Receive content, products, events as well as relevant industry updates from The Medicine Maker and its sponsors.
Stay up to date with our other newsletters and sponsors information, tailored specifically to the fields you are interested in

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].
If you wish to unsubscribe, you can update your preferences at any point.

About the Author
Stephen Brown

Stephen Brown is Managing Director at Capsugel, Edinburgh, UK.

Register to The Medicine Maker

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:
  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Medicine Maker magazine