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


Thin-film technology

Thin-film technology is a relative new area of interest with respect to oral fast-dispersing products. Although not strictly an ODT, the oral thin-film platform provides an alternative to traditional tablet approaches.

Oral thin films generally consist of hydrophilic polymers of varying thickness (50 to 200 nm). The manufacturing process is based on liquid casting to control film and weight variability. The dosage required is achieved by manipulating the API concentration in the bulk solution and/or the film-thickness produced. The films are dried by passing through oven(s) to evaporate the solvent used to prepare the film. The dried film is cut into single unit doses before packaging. During manufacture, the dried film must be protected from heat and humidity. The final packaging of the strips also needs careful consideration to protect the product from moisture. Taste-masking options include the use of sweeteners, flavors, and ion-exchange-resin complexes. Encapsulated APIs for taste-masking purposes is challenging because the larger particles can give rise to uniformity issues.


Table V: Examples of products using thin-film technologies.
Although disintegration of thin films are rapid (< 30 s), their limitation is drug loading (approximately less than 30 mg). Increasing film-thickness or using multiple layers may increase drug loading, but greater thickness can have a negative effect on disintegration. The specific packaging requirements also add complexity and cost to these products, though specific packaging technologies such as Catalent's DelStrip pack are being developed to suit the thin film strips. To date, the majority of products have been in the over-the-counter sector (see Table V).

Summary

The 2008 FDA industry guidance on ODTs (2) provides recommendations that clarify the expectations of the ODT dosage form. ODTs were originally developed for, and are mostly associated with, good patient acceptance and compliance. The FDA guidance reinforces such thinking by focusing on disintegration time and unit size in the context of what does and does not constitute an ODT because these two parameters heavily influence ODT patient acceptance and compliance.

Lyophilized ODTs were the first ODTs to market and have been successful in terms of sales value, sales volume, and number of worldwide product approvals. Lyophilized ODTs have proven to be versatile, by spanning a range of clinical applications (e.g., bioequivalence, buccal uptake, and stable formulations of macromolecules.) Having set the original standard for ODTs, the lyophilized products provide the additional assurance of compliance with the FDA guidance.

Compressed ODT formulations provide the convenience of using standard tableting technology and taste-masked APIs. Specialty companies can apply this technology, but the availability of super-disintegrants also make this technology accessible for in-house pharmaceutical development. Products made via compressed tableting and with sugar-floss systems can also meet the FDA ODT guidance by going through some further product optimization with respect to disintegration time. Possible compromise on upper-dose strength (i.e., tablet weight) may be required. The tablet size and weight may be negated if it can be demonstrated that all components are soluble and leave minimal residue. Thin films provide a potential alternative to ODTs which, if the dose limitations can be resolved, may also find wider application. In all cases, overall patient acceptability remains a prime consideration.

In addition to meeting the FDA guidance recommendations, palatability remains a factor that may influence the choice of ODT technology for a specific API. The relative importance of these factors in meeting the overall product criteria needs to be established on an individual basis and prioritized accordingly. However, if the defining characteristics of disintegration time and unit size cannot be met, it should be recognized that an alternative, non-ODT dosage form may need to be developed.

Rosie McLaughlin is a technical director and Susan Banbury, PhD, is a project manager, both at Catalent Pharma Solutions in Swindon, UK. Kieran Crowley*, PhD, is a manager of Zydis formulation and preformulation at Catalent Pharma Solutions, 14 Schoolhouse Road, Somerset, NJ 08873, tel. 732.537.6200,

*To whom all correspondence should be addressed.


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