# Presentation: 110123

## Advisory Committee for Pharmaceutical Science and Clinical PharmacologyJuly 22 -23, 2008

- Classification of Orally Disintegrating Tablets

**Frank O. Holcombe, Jr., Ph.D.    Associate Director for Chemistry    Office of Generic Drugs                        July 23, 2008**

## Classification of Orally Disintegrating Tablets

**Issue**
**	****Orally Disintegrating Tablets are considered a distinct dosage form by the Food and Drug Administration.  The dosage form definition describes expected functionality – i.e., disintegration.  Because of the general nature of the definition, questions remain about variations and scope of the dosage form.  The development of effective guidance is important for characterization and evaluation, but has been impeded by difficulty in determining meaningful criteria for this dosage form.**
**	****  **

## Classification of Orally Disintegrating Tablets

- Initial Products
- 	Produced by lyophilization
- 	Formed in blister packaging cavity
- 	Cake-like
- 	Porous/Glassy state
- 	Fragile
- 	Low weight
- 	Designed to dissolve/disintegrate on contact with saliva

## Classification of Orally Disintegrating Tablets

- Initial Products
- 	Intended as a treatment advantage for target 	populations
- 		Trouble swallowing (pediatric, geriatric, 			dysphagia)
- 		General compliance issues
- 		Convenience

## Classification of Orally Disintegrating Tablets

- Initial Products
- 	Considered to be a new and distinct dosage 	form
- 		Physical form
- 		Manufacturing technology
- 		Administration and use

## Classification of Orally Disintegrating Tablets

- Initial Products
- 	Defined as:
- 	Tablet, Orally Disintegrating
- 		A solid dosage form containing medicinal 			substances which disintegrates rapidly, usually 			within a matter of seconds, when placed upon 			the tongue.

## Classification of Orally Disintegrating Tablets

- Other Tablet Forms Based on Method of Use
- 	Tablet, Chewable
- 	Tablet, Dispersible
- 	Tablet, Effervescent
- 	Tablet, for Solution
- 	Tablet, for Suspension
- 	Tablet, Orally Disintegrating, Delayed Release
- 	Tablet, Soluble

## Classification of Orally Disintegrating Tablets

- Technology Development
- 	Manufacturing process shift from lyophilization to 	direct compression
- 		Simpler process
- 		Less time consuming
- 		Less expensive
- 		Avoids patented technology

## Classification of Orally Disintegrating Tablets

- Technology Development
- 	Direct compression tablet
- 		Allowed use of common tablet 			excipients
- 		Larger tablet than lyophilized product
- 		More robust product

## Classification of Orally Disintegrating Tablets

- Technology Development
- 	Tablet disintegration aided by
- 		Soluble binders
- 		Effervescence
- 		Superdisintegrants

## Classification of Orally Disintegrating Tablets

- Challenges
- 	“Orally Disintegrating Tablet” should represent 	a dosage form easily distinguishable from 	other tablets
- 	Definition includes “disintegrates rapidly, 		usually in ... seconds”

## Classification of Orally Disintegrating Tablets

- Challenges
- 	Trend to Compressed Tablets
- 		Larger tablets
- 		Longer disintegration times

## Classification of Orally Disintegrating Tablets

- Challenges
- 	Question of
- 		When is a tablet no longer an ODT?
- 		Important issue in product labelling
- 		Critical issue for 505(j) products 			(ANDAs) because of requirement to be 			same dosage form as the reference 			NDA product

## Classification of Orally Disintegrating Tablets

- Guidance Development
- 	Early Considerations included
- 		Disintegration times of less than 60 			seconds
- 		Labelling description of product 			characteristics

## Classification of Orally Disintegrating Tablets

- Guidance Development
- Current Draft Guidance
- 	General discussion of intention of dosage form
- 		Should disintegrate or dissolve rapidly 			on contact with saliva, eliminating need 			for chewing or swallowing intact tablet, 			or taking tablet with additional liquids.

## Classification of Orally Disintegrating Tablets

- Guidance Development
- Current Draft Guidance
- 	General discussion of expectations for dosage form
- 		General product development considerations
- 		Recommendation for in-vitro disintegration time 			of no more than 30 seconds
- 		Recommendation for use of USP <701> 			disintegration test method
- 		Suggested tablet weight limitation of 500 mg

## Classification of Orally Disintegrating Tablets

- Public Comments on Draft Guidance
- 	Tablet Weight – Several OTC products larger than 500 				mg
- 		          - Would restrict use for high dose drugs
- 		          - Issues can be addressed by formulation
- 	Disintegration Time – Should not be 60 seconds (can be 				higher or lower)
- 		          - USP <701> not an appropriate method
- 	 	          - in-vivo/in-vitro correlations not good

## Classification of Orally Disintegrating Tablets

- Public Comments on Draft Guidance
- 	Disintegration Time – in-vitro criteria not 				relevant to successful use of 				product
- 	In-vivo Evaluation – should be required, 				including sensory evaluation and 				palatability

## Classification of Orally Disintegrating Tablets

- Questions
- What properties (*in-vivo *or *in-vitro*) do you consider critical to this dosage form?
-  Should physical properties (e.g., size, formulation, and disintegration times) be a primary factor in determining conformance to this dosage form? (Yes/No/Abstain)
- If so, how specific or restrictive should the criteria be?
- 3. Can labeling (i.e., instructions for use) be considered sufficient to define the dosage form? (Yes/No/Abstain)
- If so, should labeling describe/include differences between/among NDA and ANDA products?
- 4.  What, if any, special issues should be considered (e.g. Patient compliance, target populations/conditions)?