Enhancing Mannitol’s Excipient Properties

Mannitol has been shown to improve patient perceptions of tablet flavor and mouthfeel, but its use can add to tableting challenges. SPI Pharma has developed new grades of material designed to make it easier to manufacture in patient-centered formulations.

SPI Pharma has expanded its Mannogem mannitol product line for use in oral solid dosage (OSD) forms, offering a new Precious Gem Collection. Its goal is to address challenges that the crystalline sugar alcohol excipient poses for formulators, particularly in patient-centric dosage forms such as orally disintegrating and chewable tablets. 

Although consumer research has found that use of mannitol can improve perceived aesthetics and taste in pharmaceutical tablets (1), formulations using the excipient can pose technical challenges during formulation and OSD manufacturing. The company extended its line with multifunctional grades of materials designed to offer better binding and disintegration profiles, greater compressibility, and tighter particle size distribution (PSD) ranges. 

“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 collection is a response to their needs and provides formulators the ability to develop smaller tablets with faster disintegration times, enhancing patient adherence,” said SPI Pharma president and CEO Jeanne Thoma at the time of the expanded product line launch on March 24, 2020.  

The company’s Mannogem XL Opal and Ruby products, for example, have been improved to help formulators use mannitol effectively in sophisticated dosage forms, such as multiple unit particle systems (MUPS) and controlled-release (CR) ODTs, so that final products exhibit better hardness, drug-loading capabilities, and friability.  The new grades also require less binder and can be made at lower compression forces. Mannogem XL Opal enables higher production rates by allowing press speeds to be increased. “Formulation is always challenging, and the advantages of mannitol have always been offset by the extra complications that it poses during formulation. These new products provide our customers with a solution that leverages the patient-centric benefits of mannitol while avoiding common formulation problems and simplifying manufacturing,” added Sarath Chandar, chief scientific officer, SPI Pharma’s Applied Innovation Group. SPI Pharma’s expanded line also includes Mannogem Emerald (25-μm diameter PSD) and Onyx (50-μm diameter PSD) product offerings.

The company, which offers formulary and other formulation development services to pharma clients, established two separate business units three years ago; one focused on excipients and the other on antacids. SPI is currently one of few mannitol suppliers that is focused only on pharmaceutical applications. 

Reflecting the industry’s move to formulations that are more pleasant and convenient for patients to take, and more likely to induce their adherence with doctor’s prescriptions, SPI has been concentrating efforts on improving products so that they can more readily be used in patient-centric dosage forms, says John McInerney, general manager of excipients and drug delivery at SPI Pharma. 

“We’re looking closely at dosage forms, and the needs of different patient groups to ensure that our products can enhance formulations by making the finished drug easier for healthcare providers and caregivers to administer and for patients to adhere to, and more pleasant for patients to take,” he says. This has meant creating proprietary technology that improves mannitol’s performance as an excipient, he explains, for name-brand, generic, and over-the-counter formulators.

Rather than developing novel excipient blends using mannitol, SPI is promoting new blends of pre-approved compendial products. The blends involve materials that are already well understood and can be quickly implemented in existing formulations, particularly newer formulations designed for once daily dosage and more convenient delivery forms, says Coralyn Gonzalez, global head of sales for excipients and drug delivery systems. 

The company is also promoting its existing services division, which was established over a decade ago to help customers develop formulations based on end-use targets and to get to a full formulary ready for clinical trials, says Bill McCarthy, the company’s global marketing manager for excipients and drug delivery systems.  

Outcomes-based healthcare and the importance of a B2C focus

As McInerney explains, SPI Pharma is targeting business to consumer issues in order to strengthen its business to business connection with pharmaceutical formulators.  Patient focus is becoming an important business strategy, given the overall move in healthcare to demonstrating product effectiveness and good patient outcomes.  “Pharmacy benefit managers are already reimbursing providers based on outcomes. The market is heading toward a situation where reimbursement will depend on how well patients comply with physician’s directions,” he says.

As a result, he says, success in drug delivery, whether on the branded side or with generics and OTCs, is moving far beyond considerations of API efficacy. “In the OTC and nutritionals markets, patient/consumer outcome is being driven by adherence, which, in turn, depends on aesthetics and how pleasing a formulation is to the consumer, says McInerney. Increasingly, brand name, OTC and generic pharmaceutical manufacturers are factoring both API performance and these consumer values into new formulations to drive business, he says. “Companies can now enhance the perceived value of APIs with more aesthetically pleasing dosage forms,” he says.

SPI designed its materials to balance better performance with better consumer properties. “With the new products, formulators that had been using other grades of mannitol with different PSDs or critical quality attributes, will be able to maintain the same process conditions and achieve higher throughput API loading, better process economics, while maintaining improved mouthfeel patient satisfaction for the same formulation. Manufacturers can produce more tablets per hour and increase the amount of API loading per tablet, which allows them to create new forms without taking risks,” McCarthy says.

Differentiating for pharma

Where excipient suppliers are usually large companies that provide commodity-grade materials for a wide variety of industrial end users, SPI Pharma has found it important to focus on pharmaceutical formulators’ requirements, and to emphasize compliance with current good manufacturing practice (CGMP) requirements first, says McInerney. A crucial requirement is controlling manufacturing processes so that product is consistent from batch to batch, says Gonzalez.  “Having GMP processes in place assures that our processes are in control, and we are providing materials that enable higher API loadings and product form factors,” she adds. 

Reference

L. Ohrem et al, Pharmaceutical Development and Technology 45(10), 2013.