Excipient innovation for enhanced patient compliance: part I

Formulation can be challenging, particularly when working with excipients such as sugar alcohols. However, a new line extension from SPI Pharma offers a solution that leverages the patient-centric benefits of mannitol while avoiding common drug development problems and simplifying manufacturing

By expanding its line of Mannogem® Mannitol products for use in multiple patient-friendly oral dosage forms, SPI Pharma has applied its proprietary manufacturing technology to address mannitol’s inherently poor compressibility.

Producing multifunctional, compendial grades of mannitol with superior binding and quick disintegration properties, greater compressibility and tight particle size ranges, the company’s new excipients are ideal for the formulation of convenient, patient-friendly dosage forms, such as orally disintegrating tablets (ODTs) and chewables.

Offering smaller tablet sizes and faster disintegration times, further enhancing patient compliance, they broaden the options to overcome issues with challenging formulations, such as content uniformity, poor API compressibility and improved organoleptics.

Commenting on the launch, SPI Pharma’s Jeanne Thoma, President and CEO, said: “SPI Pharma is excited to be launching the Mannogem Mannitol Precious Gem Collection. These new grades align with our core purpose of making a difference in patient adherence. Our customers identified an unmet need in their development efforts."

"The extension of our Mannogem Mannitol product line reflects our commitment to go beyond what our customers are seeking by assessing the market and anticipating their needs, as well as the needs of their customers.”

Wishing to find out more about what the line extension means for the company and the greater pharmaceutical industry, Dr Kevin Robinson recently caught up with John McInerney, General Manager, Excipients and Drug Delivery Systems (EDDS), Bill McCarthy, Global Marketing Manager, EDDS, and Don Loveday, Global Business Development Manager, to dig a little deeper.

John explains: “It’s a new chapter for us. SPI is known in the industry for our innovation, our quality and our customer service. Regarding our products, we’re predominantly the only pharmaceutical company that produces mannitol products for the pharma sector. As such, our customers see us both as an innovator and, at the same time, a quality supplier of products.”

“We’re also well known for our technical service; our clients recognise that we will be a partner with them. Not only do we provide outstanding products and exceptional customer service, we also provide them with technical understanding regarding how to use the products."

"Many of us at SPI have only actually been with the company for less than 2 years. But this was part of Jeanne’s strategy when she joined the organisation 3 years ago … to realign our focus on what we see as our core value. And that’s providing exemplary quality and service to the pharma industry in the excipient and drug delivery areas."

"We’re constantly assessing the business landscape, listening to what our customers want and, as a result, we recognised that there were some potential opportunities in our portfolio to expand. Based on that information, we very quickly developed four new product line extensions for our mannitol products.”

Describing how the new products fit into SPI’s portfolio and what they offer the industry, Bill adds: “What we’ve done is added four products to our mannitol range. Mannitol represents part of our core expertise and our ability to bring innovation and technical expertise to pharma formulators, so it was a natural extension for us."

"For pharma companies in particular, there’s a growing and critical requirement for formulations to service the needs of sensitive populations, such as geriatrics, paediatrics, etc. Mannitol is uniquely suited to those types of applications — making oral solid dosage (OSD) forms easy to dose, patient friendly and pleasant, which improves compliance and adherence. Based on a technology that enhances the performance of mannitol in direct compression manufacturing processes, that’s what these products are all about!”

“What that means,” he continues, “is that people can start using mannitol a little bit more easily, more cost-effectively, to develop the much-needed OSDs that have been difficult to formulate in the past. That’s the key reason why this launch is important for us, fits within our strategy and complements the types of products we already have."

"By offering a familiar package — compendial mannitol — the industry is already familiar with the product and understands how to use it. They can slot it right in to their formulations, benefit from the line’s enhanced performance and be able to start making the OSDs that will meet the unmet needs of patients.”

Exploring the drivers behind the launch, I wonder whether the line extension was a customer-inspired development. “Absolutely,” notes John: “SPI is very much a customer- and patient-centric company. We understand that Big Pharma is inherently risk averse; yet, it’s also looking for new tools that will enable them to develop new formulations and new products that enhance the customer experience. To address that, we’ve taken an industry staple, compendial mannitol, which is already available in very specific forms, and been able to improve it so that it now has better properties.”

“For instance,” he adds, “our mannitol has better compactibility, so it can accommodate more active loading. More importantly, though, it might be able to reduce the total production cost of finished dosage forms. As such, we’re taking the risk out … but putting new functionalities in.”

Mannogem XL Opal and Mannogem XL Ruby enable formulators to efficiently develop sophisticated dosage forms, such as multiple unit particle systems (MUPS) and controlled-release (CR) ODTs. These products maintain the same properties as standard compendial mannitol, with the added benefits of SPI Pharma’s proprietary technology.

Tablets formulated and produced using Mannogem XL Opal and Mannogem XL Ruby exhibit higher hardness, faster disintegration per tablet hardness, higher drug-loading capability and significant reduction in friability. They also require less binder and can be made at lower compression forces.

Mannogem Emerald and Mannogem Onyx: by broadening its portfolio with these two popular mannitol powders, SPI Pharma will enable customers to formulate with the confidence of a secure supply chain. When this confidence is combined with the expert technical service available through its dedicated pharmaceutical formulation staff, customers working with SPI Pharma are propelled to successful commercial launches.

Production considerations

Cycling back to the topic of direct compression (DC), I suggest that this is an established process that’s on the rise because of the evolution of continuous manufacturing. I ask whether this was a consideration before the launch or just a happy coincidence.

Don, believes that, for SPI, the DC process is always an important starting point. “We see it as one of the most efficient ways for people to produce tablets. So, ultimately, if we’re trying to meet patient needs, the best way for manufacturers to do that in a cost-efficient way is by direct compression. And a lot of our expertise is based on ensuring that mannitol can enable the DC process while simplifying both manufacturing and formulation.”

“There are a couple of things here to tie together,” he continues: “As a long-term supplier to the industry, we’re known for developing highly specialised mannitol-based formulations for customers, so much so that we have a business line that effectively acts as a business-to-business (B2B) contract service to help customers optimise their formulation according to specific business-to-consumer (B2C) needs."

"For example, the global prevalence of paediatric investigation programmes — as required for regulatory approvals — has grown from a dozen or so in 1990 to more than 200 today. If you think about it, that’s a good proportion of all the drugs that are seeking approvals. Many of those are novel therapies being developed for people younger than 18 … and the preferred dosage forms for those populations are not injectables or parenterals! In fact, they’re the least preferred options because they’re poorly tolerated and adhered to.”

Explaining further, Don adds: “There’s a need and a market; but, beyond that, what end users want is a palatable dosage form that’s readily available. An example would be a promising non-vaccine therapy for COVID-19 or its symptoms."

"Right now, there’s an unaddressed population out there. SPI is set up to serve the B2C market that our customers face without adversely affecting their B2B activities; with direct compression, for example, you can produce very low dosage forms that are appropriate for paediatrics that are both palatable and sugar-free (mannitol is a sugar alcohol). So, we’re thinking both about our customer’s customer and the very long-term needs of the market.”

Challenges and drivers

Given the changing nature of the excipient market, the rise of biosimilars, nanotechnology, personalised medicines, etc., I ask SPI whether they see these developments as threats or opportunities? “From the marketing side,” says Bill, “we see them as both. We’ve observed what’s going on with biologics, biosimilars and what we call biosimilar excipients, and see it as an entirely new way to think about the excipient space. It’s very much an opportunity and a challenge.”

“If you look at our customers’ pipelines for example, we still believe that the most sought-after dosage form is going to be an OSD. Sure, there are a lot of monoclonal antibodies in development, which will be delivered as injectables, but we’re convinced that OSDs will remain the most popular route of administration."

"If we remain focused on the needs of our customers and patients, we’ll retain our place in the market. It’s certainly an evolutionary environment that’s ever changing, but we feel we have a right to stay in the game and truly believe that we have products that bring real benefits to people that are going to have to take those drugs.”

“When you’re sitting inside a drug company,” adds Don, “and you’re planning to develop a new molecule or a new dosage form for an existing molecule, one of the choices you make — often at the last minute — is how to get that drug into the human body. For example, there are lots of Phase III trials for injectables because Company X might not want to focus too much on the delivery system prior to approval."

"The simplest way to get a drug into the body is via injection (as opposed to inhalation or oral). But, what I want to point out is that the utility of other routes of administration is not our primary focus; what we want to do is use the appropriate dosage form for the population and then work backwards from that to deliver the drug. Compared with the teams that are developing the drug molecules, we’re looking at the process from the other end of the pipeline.”

“We’re trying to think about how we can provide solutions for classes of molecules such as monoclonal antibodies, peptides or multicomponent antiretrovirals. Because those problems exist today, we are trying to solve them in a way that allows new tools to be available to the people who are developing formulations earlier in the drug cycle. I think that that reflects SPI’s focus on being both customer- and patient-centric. That’s that we bring to pharmaceutical companies; we can help them to get their drug to market in a form that patients want to take,” he concludes.

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