Orally Disintegrating Tablets: The Effect of Recent FDA Guidance on ODT Technologies and Applications - Pharmaceutical Technology

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Orally Disintegrating Tablets: The Effect of Recent FDA Guidance on ODT Technologies and Applications
The authors describe the various available technologies used in orally disintegrating tablets.


Pharmaceutical Technology


FlashTab and Pharmaburst. FlashTab (Ethypharm, Saint Cloud, France) and Pharmaburst (SPI Pharma, Wilmington, DE) technologies rely on the use of super disintegrants. Flashtab is a combination of wet and dry granulation before compression. Microparticles of taste-masked API are blended with conventional tableting aids and disintegrants such as polyvinyl polypyrollidone or crospovidone (cross-linked PVP), cross-linked sodium carboxymethyl cellulose (cross-linked CMC) and swelling agents such as starches or microcrystalline cellulose. Disintegration times are typically less than 1 min.

The Pharmaburst ODT uses a proprietary disintegrant (Pharmaburst) that is based on mannitol blended with conventional tableting aids. The excipient system is claimed to be of good flow characteristics and highly compressible such that robust tablets can be produced while maintaining disintegration times of 30 s or less depending on the drug loading.

Other excipients promoted for the formulation of ODTs using conventional tableting technology include BASF's (Florham Park, NJ) Ludiflash, a mannitol/crospovidone/polyvinyl acetate combination, and Fuji Chemical Industry's (Toyama, Japan) F-Melt, a cospray-dried powder combining inorganic excipients and disintegrants dispersed in a carbohydrate complex.

AdvaTab. The AdvaTab (Eurand Pharmaceuticals, Dayton, OH) system incorporates the microencapsulated API (Microcaps, Eurand Pharmaceuticals) for taste-masking purposes. This ODT platform relies on the fact that AdvaTab tablets are compressed using a patented external lubrication system in which the lubricant is only applied to the tablet surface. AdvaTab tablets can be manufactured using low-compression forces and permit ingress of moisture on contact with saliva. AdvaTab tablets are claimed to be robust and to disintegrate rapidly in the oral cavity. The tablet-compression step does not lead to breakage of the drug particles.

The advantage of the compressed tablet ODT platforms is that they are able to accommodate taste-masked APIs, either by microencapsulation or within a taste-mask matrix, with relative ease. However, the compression forces used need to be carefully balanced to avoid compromising the taste-masking coat or rapid disintegration time while still achieving sufficient cohesion within the tablets for adequate handling robustness.

As indicated in Tables III and IV, disintegration times for the compression ODTs tend to be longer. The levels of excipients required (including taste-masking materials) in the finished product are typically higher than for the ODT technologies using lyophilization.

Sugar-floss systems

Biovail's (Mississauga, Canada) Flashdose system is an example of a sugar-floss system. This system involves producing fibers from molten sacharrides (sucrose, dextrose, or lactose) or polysacharrides. The floss fibers are blended with API and other excipients and compressed into tablets. There is usually a conditioning step at elevated temperature and humidity to ensure complete conversion of amorphous sugar fibers to crystalline material. This system relies on the highly soluble nature of the sugar components as well as the formulation porosity to achieve rapid disintegration.

Molded tablets

Molded tablets are based on a technology platform that uses water-soluble ingredients such as sacharrides (lactose, mannitol, or maltose) that cause the tablets to disintegrate and dissolve rapidly. Typically, the powder blend is moistened with a hydro-alcoholic solvent and molded into a tablet using low-compression pressure. The wet-compressed mass is air dried.

The manufacturing process for the WOWtab (Astellas Pharma, Yamanouchi, Japan) product involves granulating highly soluble low-moldable sugars (e.g., mannitol, lactose, glucose, sucrose) with high moldable sugars (e.g., maltose, maltitol, and sorbitol). Following compression, there is a humidity conditioning step to increase product robustness.


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