The regulatory agency may request samples for evaluation of the physical attributes of a tablet or capsule during review of ANDA. This guidance discuss about size, shape, and other physical attributes of generic tablets and capsules.
Generic drugs are both pharmaceutically and therapeutically equivalent to a RLD/RS (RP), but its physical characteristics (e.g., size and shape) should be in line with RP to acheive Patient compliance & avoid medication errors.
It is important because:
1. Many individual finds difficulty in swallowing tablets and capsules.
2. Over 16 million people in US have some difficulty swallowing, also known as dysphagia.
3. This problem goes well beyond the patient population with clinically recognized dysphagia and may affect as many as 40 % of Americans.
4. Of those who experience difficulty swallowing, less than a quarter discuss the problem with a health care professional.
5. 8 % admit to skipping a dose of prescribed medication.
6. 4 % have discontinued therapy because the tablets and/or capsules were difficult to swallow.
7. Size and shape of tablets and capsules affect the transit through the pharynx and esophagus.
8. Larger tablets and capsules have been shown to have a prolonged esophageal transit time.
9. This can lead to disintegration of the product in the esophagus and/or cause injury to the esophagus, resulting in pain and localized esophagitis --> ulceration --> stricture --> perforation.
10. Other adverse events such as pain, gagging, choking, and aspiration are related to swallowing difficulties.
11. studies suggests that tablet sizes greater than approximately 8 mm in diameter cause swallowing difficulties.
12. Tablet Shape:
12.1: flat tablets have greater adherence to the esophagus than capsule-shaped tablets.
12.2: oval tablets may be easier to swallow and have faster esophageal transit times than round tablets of the same weight.
FDA introduces this guideline to address the above mentioned problems.
Recommended Tablet Size
1. If the RLD is less than 17 mm in its largest dimension, the generic product should be:
> No more than 20 percent larger than the RLD in any single dimension (the resulting single dimension of the generic should not exceed 17 mm).
> No more than 40 percent larger than the volume of the RLD.
2. If the RLD is equal to or greater than 17 mm in its largest dimension, the generic product should be:
> No larger than the RLD in any single dimension.
> No larger than the volume of the RLD.
3. The largest dimension of a tablet should not exceed 22 mm and that capsules should not exceed a standard 00 size.
4. Additional flexibility may be given for products that are 8 mm or smaller in their largest dimension, but efforts should be made to develop Tab & Cap that are of a similar size and shape to the RLD.
For Capsules:
Under the standard capsule size convention:
- The allowances described above will generally allow an increase of one capsule size, when the RLD capsule is of size 3 or smaller.
- When the RLD capsule is of size 2 or larger, an increase of one capsule size should only be considered when adequate justification can be provided for the size increase.
- These recommendations would allow an increase of one capsule size when the capsule size is less than capsule size 00.
Recommended Tablet Shape
FDA recommend --> manufacturing tablets and capsules that have -->
- Similar shape or have a shape that has been found to be easier to swallow compared with the shape of the RLD.
- Evaluating and comparing the largest cross sectional areas of the RLD and generic product is one strategy to quantify changes in shape.
- Tab or Cap that have a larger cross sectional area (e.g., tablets that are rounder) would generally be more difficult to swallow than that of same volume but with smaller cross sectional areas.
This guidance also include following recommendations:
- tablet coating,
- weight,
- surface area,
- disintegration time
- propensity for swelling
Related: Types of Pharmaceutical Tablets