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Discovery & Development Formulation, Drug Delivery, Small Molecules, Ingredients

Going Granular with Microparticulates

The business model of pharmaceuticals has changed. The industry is no longer about blockbuster drug development, but about patient outcomes and product lifecycle management. This new era emphasizes efficiency in development and manufacturing – and, as a result, we’re all looking for cost-effective solutions that can expand a product’s applicability to a broader range of patients. Many new formulation approaches have been developed to create more patient-friendly medicines – from improving swallowability to reducing the number of doses that a patient must take.

One approach that I am very familiar with – and a current “buzzword” – is microparticulates. Either microspheres or microcapsules (offering a distinct “core” and “shell” layer), microparticulates are defined by a diameter in the sub-millimeter range. Think of them as micro-sized pills. Some of their advantages over larger, traditional capsules include greater flexibility in design, improved bioavailability and stability, and predictable gastric residence time, which means less inter- and intra-subject variability.

However, when considering the use of microparticulates in formulation, it’s easy to get bogged down by the countless manufacturing approach variations: spraying, spinning, congealing, extruding, coating, coating... and coating again. Multiple coating steps are applied to attain different release kinetics or behaviors from microparticulates. One layer may be used for drug stability, a second layer for pH-dependent release, and a third layer for taste-masking.

The inclination to use microparticulates often arises when one or more incompatibilities exist between standard dosage formats (tablets, capsules, gel caps, caplets, and so on) and the terminal use profile. Such an incompatibility may exist in theory, formulation, manufacturing, packaging, stability, user experience, drug product performance, clinical efficacy, or long-term clinical outcomes. For example, microparticulates dosage forms can be used to help circumvent food effects because of the relatively small and dispersible size, or to help improve disintegration and dissolution speed. The size can also be a key formulation consideration to improve efficacy when delivering drugs to the small intestines.

But perhaps one of the most important attributes of microparticulate dosage forms is their ability to address patient compliance by providing patient-friendly forms for those unable (or unwilling) to swallow a traditional oral solid. With patient and patient outcomes taking center stage, there is growing emphasis on catering to pediatric populations, as well as patients with dysphagia or organoleptic proclivities, or individuals suffering from serious mental illness. Traditionally, a liquid formulation would be used for these patient populations, but liquid forms are not always a good option, usually because of stability or taste considerations (the latter point being especially true for children). Microparticulate formats, however, can offer improved stability when delivered via a sachet format, or can be reconstituted immediately prior to administration. They can also offer taste masking when the API is appropriately encapsulated.

I believe that microparticulate dosage forms can help enhance the user experience.

Although microparticulates do have many advantages, there are some realities that need to be faced. Microparticulates are manufactured through a variety of different processes. Modified release is a popular use of microparticulates and generally relies on sequestration of the API via one or more physicochemical mechanisms, which require multiple manufacturing steps (just like traditional tablets). Formulating a powder, however, presents unique coating challenges because of the high surface area to volume ratio of particles, as well as the irregular overall diameters of particles within the powder bulk. The design and manufacturing required to ensure predictable performance and high quality of the final product can be challenging, considering these constraints.

With any dosage form, clinical efficacy and long-term clinical outcomes all rely heavily on the drug being taken as designed and prescribed. Groundbreaking chemistry, cutting-edge stable formulations, manufacturing finesse, and ultra-cool product packaging are all meaningless if nobody ingests the product. Non-adherence is a significant problem – and it perpetuates patient suffering, increases clinician involvement, and results in unnecessary healthcare costs.

I believe that microparticulate dosage forms can help enhance the user experience – when made correctly. If your team decides that a particle format would be the perfect solution, then you should be very thoughtful about the design and execution, because so much relies on it. Does the microsphere need multiple layers of functionality? Is there a simpler way to achieve the result? Next-generation microparticulate technologies are offering simplified approaches that allow controlled release powders in a single-step process. Such controlled release powders can act as a building block for a multitude of format options, which simplifies product life cycle management for pharmaceutical companies.

Microparticulates are emerging as a drug-delivery technology with significant benefits, not least their ability to produce patient-friendly products and superior patient outcomes. Right now, too many underserved patient populations are crushing tablets or using extemporaneous formulations – and that can only lead to unnecessary patient risk. I believe that the industry has a duty to ensure that medicines are being used correctly – and that means that they need to be available in patient-friendly forms.

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About the Author
Nathan H. Dormer

Nathan H. Dormer is Vice President of Research and Development at Orbis Biosciences, Lenexa, Kansas, USA.

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