Is another ODT excipient necessary?

Sep 01, 2009
Volume 21, Issue 9

Formulations for tablets with fast melt characteristics were originally demanded for special patients and indications, where swallowing tablets led to poor patient compliance, particularly in children and geriatric patients.1 Soon after, however, the market demanded more of these easily administrable formulations and companies realized their marketing advantage compared with conventional tablets; the ability to take tablets anywhere without water for swallowing made them more attractive. Moreover, companies regarded this new formulation and administration route as a product lifecycle extension — a strong economic driving force these days. Soon, this special application niche was named ODT — orally dispersible tablet.

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Fast disintegrating formulations have long been available, but how do ODTs differ from other technologies? The answer is not straightforward because definitions of an ODT vary: the US Pharmacopeia describes an ODT as a tablet with a disintegration time of <30 s; whereas the European Pharmacopoeia gives a disintegration time of <180 s.2,3 Ultimately though, it is the therapy's acceptance in the market as well as the patients that have coined the definition of an ODT: a tablet that dissolves quickly in the mouth without water, and has a pleasant mouth feel and taste, without an adverse aftertaste (if the mouth feel or taste are unpleasant even the shortest disintegration time will be too long!).

ODTs can be categorized into two main groups: lyophilized formulations and directly compressed tablets. Thin film strips are a third category, but are limited in dosage up to approximately 30 mg. This technology does, however, keep its niche for certain actives; for example, in cold and flu indications. Lyophilization plays a minor role owing to its cost and difficult handling, though it does remain important for very sensitive drug molecules. Undoubtedly, the greatest interest of pharmaceutical formulators is in direct compression, because it is a cost-effective production technology with a broad application range that has the least limitations with regards to the active. Furthermore, the finished product resembles what patients are used to, which guarantees good acceptance and aids compliance.

Numerous excipient systems for ODT applications are already available on the market including, for example, Pharmaburst, F-Melt and Ludiflash (directly compressed ODTs), and Pharmafreeze, Zydis and Lyoc (lyophilized ODTs). One might, therefore, ask the question: is there a need for yet another basic excipient system for direct compression and fast disintegration? We believe the answer is "yes".

Developing a two-component excipient

As a minimum requirement, most directly compressed ODTs rely on the inclusion of a sugar alcohol combined with a superdisintegrant. The use of superdisintegrants has been widely described; they are generally accepted as a necessary component of ODT formulations to speed dissolution.4,5 Another important feature of an ODT is its taste; it must taste good otherwise the product will never get off the ground. In general, polyols are known to exhibit a sweet taste and a pleasant mouth feeling, with mannitol being one of the most commonly used of this class because of its crucial qualities; it is not hygroscopic, it is stable and it is inert to virtually all APIs.

However, polyols are not thought to be sweet enough to mask bitter-tasting actives, and are, therefore, deemed to be insufficient for taste-masking in ODT formulations. As a result, they are hardly used as sweeteners in pharmaceuticals and instead serve as effective binders. A supersweetener, such as aspartame or sucralose (sucralose does not exhibit the same unpleasant aftertaste as most other sweeteners and has a similar, pleasant taste to sucrose), may be better in this scenario.

When considering ODT excipient systems, it is nonsensical to include a sweetener at this stage because its dosage will be dependent on the nature and taste of the active and other ingredients.

Most ODT excipient systems on the market contain more than the two essential components; that is, they include several binders and a superdisintegrant. Thus, the amount of regulatory work required for registration increases with the greater number of components added. We believe that this work could be significantly reduced if all ODTs only contained two components: one binder plus a superdisintegrant.

Parteck ODT is a combination of spray-granulated D-mannitol (a binder) and croscarmellose sodium (a superdisintegrant). Both are well accepted by authorities, which accelerates the registration procedure. Croscarmellose sodium is the sodium salt of a cross-linked, partly O-(carboxymethylated) cellulose.6–9 This paper examines the practical use of this new excipient system.

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