FDA provides choices of experimental conditions for conducting drug dissolution/release tests for various drug products (Link). In total there are 789 entries in the database, including 228 where readers are referred to the USP monographs and 16 without suggestions and the sponsors are to develop their own. Therefore, there remains 545 (789-228-16) entries, which are used for the trend analysis.
Breakdown of apparatuses use
|
RPM |
Apparatus# |
|
|
Paddle* |
Basket** |
|
|
25 |
11 |
– |
|
50 |
282 |
12 |
|
60 |
7 |
– |
|
75 |
82 |
8 |
|
100 |
31 |
79 |
|
Total |
413 |
99 |
*Other RPMs include (30, 40, 150, 175 and 200 =10 entries)
**Other RPMs include (40, 120, 150 and 180 = 6 entries)
#27 were others including 2 for flow-through.
Breakdown of media use
|
Medium* |
|||
|
HCl |
Water |
Phosphate |
Acetate |
|
218 Includes 0.001N =4 0.01 N= 31 0.1 N =140
|
170 |
147 pH (5 to 7) = 74 pH (7 to 7.5) = 38 pH (< 5) = 4 pH (> 7.5) = 3 |
16 pH 4 to 5 |
|
* others = 34, also see note 2 below. |
|||
There are 270 unique entries in the medium category, which may be considered as 270 different types of media employed. These differences are based on different combinations/permutations of the nature of the medium (HCl, water, phosphate, acetate, citrate etc), molarities/normalities, and pHs. If one adds to these the choices of apparatuses and their RPMs then the unique entries becomes 317.
Majority of the suggested experimental conditions appear to be based on Paddle Apparatus (413/545), using media in the pH range of 5 to 7.5 which would include water as well (317/545).
The obvious question is that if the majority of the tests can be conducted using the paddle apparatus and a medium having a pH between 5 and 7.5, such as water itself or phosphate buffer (~pH 6), then why so many unique experimental conditions? This may indicate the deficiency/limitation of current practices of dissolution testing, which should be addressed.
Notes:
-
In many cases, breakdown is subjective as it is difficult to categorize the choice e.g. the entry (Water, pH 3.0, adjusted with 0.1 N or 2 N HCl) was excluded as it neither represents water nor HCl. On the other hand, the 2 entries: (1) pH 6.8 buffer and (2) 0-2 hours: 0.003% polysorbate 80, pH 1.2 2-8 hours: phosphate buffer, pH 7.2; are considered to be phosphate buffer.
- In some cases, multiple media are suggested e.g (50 mM potassium dihydrogen phosphate buffer pH 6.5 Comparative dissolution data should also be provided in 900 ml pH 0.1 HCl, pH 4.5 buffer, and water using Apparatus II). Thus, there is a discrepancy between total number of entries and the sum of the entries for the individual medium.
