Orally Disintegrating Tablets: Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Guidance for Industry
Orally Disintegrating Tablets
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
December 2008
Chemistry

Guidance for Industry
Orally Disintegrating Tablets
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druginfo@fda.hhs.gov
http://www.fda.gov/cder/guidance/index.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
December 2008
Chemistry

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 1
III. 	DISCUSSION .................................................................................................................... 2
IV. 	DISINTEGRATION TESTING ...................................................................................... 3

Contains Nonbinding Recommendations
Guidance for Industry1
Orally Disintegrating Tablets
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.
I. 	INTRODUCTION
This guidance provides pharmaceutical manufacturers of new and generic drug products with an
Agency perspective on the definition of an orally disintegrating tablet (ODT)—which is a
different dosage form than, for example, a chewable tablet or a tablet that should be swallowed
whole with liquid—and also provides recommendations to applicants who would like to
designate proposed products as ODTs.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
II. 	BACKGROUND
In an effort to develop drug products that are more convenient to use and to address potential
issues of patient compliance for certain product indications and patient populations,
pharmaceutical manufacturers have developed products that can be ingested simply by placing
them on the tongue. The products are designed to disintegrate or dissolve rapidly on contact
with saliva, thus eliminating the need to chew the tablet, swallow an intact tablet, or take the
tablet with liquids. This mode of administration was initially expected to be beneficial to
pediatric and geriatric patients, to people with conditions related to impaired swallowing, and for
treatment of patients when compliance may be difficult (e.g., for psychiatric disorders).
1 This guidance was prepared by the Office of Pharmaceutical Science in the Center for Drug Evaluation and
Research (CDER) at the Food and Drug Administration.
1

Contains Nonbinding Recommendations
After the Agency received and reviewed applications for the initial products, the CDER
Nomenclature Standards Committee developed the following definition for an ODT as a new
dosage form in 1998:
A solid dosage form containing medicinal substances which disintegrates
rapidly, usually within a matter of seconds, when placed upon the
tongue.2
Characteristics that were exhibited by the initial products included low tablet weight, small tablet
size, highly soluble components, and rapid disintegration. Such characteristics supported the
intended uses of these products.
However, as firms started developing additional products using different technology and
formulations, many of these later products exhibited wide variation in product characteristics
from the initial products. Because this shift in product characteristics can affect suitability for
particular uses, the Agency developed this guidance for industry.
III. 	DISCUSSION
As briefly discussed in section II, an ODT has previously been distinguished as a separate dosage
form because of the specific, intended performance characteristics of such a product, which are
rapid oral disintegration in saliva with no need for chewing or drinking liquids to ingest these
products. These characteristics, which are an aid to patient use and compliance, are the primary
characteristics that constitute the basis for classifying a product as an ODT.
The recommendations in this guidance are based on the intention of the original definition and
on Agency experience with new drug applications (NDAs) and abbreviated new drug
applications (ANDAs) submitted for this dosage form. To determine what the Agency's
experience has been, we surveyed applications for products submitted to the Agency, completed
a literature review, and collected information from laboratory studies that showed that although
disintegration times ranged from a few seconds to longer than a minute, a large majority of these
products have in-vitro disintegration times of approximately 30 seconds or less. These products
represented different manufacturing technologies, a variety of tablet sizes and weights, and
various disintegration strategies, thus demonstrating that relatively rapid disintegration is readily
achievable across a variety of products.
Products labeled as ODTs should match the primary characteristics for this dosage form
(identified above). Based on the original product rationale and Agency experience, we
recommend that, in addition to the original definition, ODTs be considered solid oral
preparations that disintegrate rapidly in the oral cavity, with an in-vitro disintegration time of
approximately 30 seconds or less, when based on the United States Pharmacopeia (USP)
disintegration test method or alternative (see section IV).
2 CDER Data Standards Manual.
2

Contains Nonbinding Recommendations
Although the value of 30 seconds is given as a desired result, it is not intended to represent an
arbitrary distinction between an ODT and some other tablet form. It is instead representative of
a general time period associated with drug products that have been found to have performance
characteristics appropriate for a disintegrating tablet meant to be taken without chewing or
liquids.
We recommend that as a primary consideration when developing this type of product, you use
the defining characteristics for this dosage form designation (rapid disintegration in saliva
without the need for chewing or liquids). Products should be developed to match these
characteristics, rather than labeling a tablet as an ODT because it would eventually disintegrate
when placed in the mouth. For example, tablets that take longer than 30 seconds to disintegrate
or are dosed with liquids may be more appropriately considered to be chewable or oral tablets.
Additional parameters for consideration during product development are tablet size, tablet
weight, component solubility, and the effect these factors have on the product’s intended use.
While tablet size or weight is not explicitly included in the definition, you should consider the
effect large tablets have on patient safety and compliance. We generally recommend that the
weight of the tablet not exceed 500 mg; however, if a tablet intended for use as an ODT weighs
more than 500 mg, its ability to perform effectively as an ODT should be justified based on
product performance. For such products, the extent of component solubility (e.g., tablet residue,
need for liquids) can influence the acceptability of the product being labeled as an ODT.
IV. 	DISINTEGRATION TESTING
Part of the process of determining if a product is an ODT involves testing a product to see how
long it takes to disintegrate. Determination of disintegration time appears to be method
dependent. Some methods are more discriminating than others. To provide both a standard for
and consistency in disintegration testing, we recommend that applicants use the USP method for
disintegration testing.3 However, other methods that can be correlated with or are demonstrated
to provide results equivalent to the USP method also can be used and submitted to determine
disintegration time.
3 USP 29, <701> Disintegration, pp. 2670-2672.
3