Engineering compendial mannitol for orally dispersible applications

Regulators are increasingly insisting that formulators consider patient centricity during formulation development; as such, the organoleptic properties of the final dosage form must be considered at the start of any project, writes SPI Pharma's Graeme Macleod and Wayne Camarco

There has been a significant increase in the number of patient-centric dose forms reaching the market, with examples including orally dispersible (ODTs) and chewable tablets that meet the requisite targets of being “pleasant to take.”

Despite the evolving requirements of patients and regulators alike, the introduction of excipients that enable formulators to meet these objectives has been minimal.

SPI Pharma was the first company to launch a coprocessed excipient (Pharmaburst) that, for the first time, enabled the formulation of a directly compressible blend of active pharmaceutical ingredients (APIs) and excipients that met the requirements of ODT development.

It could withstand downstream processing and, at the same time, disintegrate quickly in the mouth and impart a positive patient experience.

The utility of such excipients could be further enhanced if formulators had access to a monographed excipient with all the benefits of a coprocessed system. With this in mind, SPI Pharma set about the development of such an excipient.

Mannitol is widely used as an excipient in oral dosage form development because of its low hygroscopicity and high stability or inertness. It has extremely pleasant organoleptic properties, a mild sweetness and exerts a minor cooling effect as it solubilises in saliva.

This has made it the preferred excipient in ODT formulations and the base for most ODT platforms. As more and more drugs are converted to patient-centric dosage forms, it was clear that mannitol had many of the requisite attributes. One barrier to its ubiquitous use, however, was its relatively low tabletability.

For a formulator, the ability of an excipient to form a robust compact is critical, particularly in ODTs, which generally rely on being highly porous or very soluble to enable rapid disintegration.

If the tabletability of mannitol could be enhanced, along with its inherent stability, inertness and pleasant organoleptics, the resultant product would be an ideal universal excipient for orally dispersed compressed tablets.

As a result, SPI Pharma scientists invented Mannogem XL technology and we recently launched two versions of Mannogem XL mannitol — Mannogem XL Ruby and XL Opal — that we believe offer formulators an excipient that not only meets existing monograph needs but has significantly improved its applicability.

Mannogem XL Ruby: Taste masking is an absolute must for certain APIs, which can be bitter or astringent in nature and would be negative in terms of patient centricity.

In the majority of cases, the taste masking approach requires the application of a polymeric membrane to granules of the drug to help mask the unpleasant taste. As a result of these taste masking techniques, the resultant particles can be quite large, which can subsequently cause segregation of the active particles from the rest of the blend.

By matching the taste masked API particle with a larger particle-sized excipient, it is possible to overcome segregation. However, until now, such grades of mannitol had lower tabletability than the smaller particle-sized spray dried grades.

Mannogem XL Ruby combines the large particle size of a granular mannitol with the tabletability of a spray dried material.

Mannogem XL Opal: By extending this same XL functionality to a spray dried product, Mannogem XL Opal further extends the utility of mannitol and makes it much more compressible.

The superior tabletability of Opal enables formulators to develop products with a drug loading capacity that was not previously possible. It also simplifies formulation by negating the need to use other binders, which can negatively affect organoleptics.

Summary

In conclusion, these new grades are the realisation of novel compendial excipients that have been developed with drug development and patient needs in mind.

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