A dissolution test for an ER products is similar to IR & DR products excepts -
- duration is longer.
- acceptance criteria include at least 3 time points.
- early time point, usually 1–2 h >>> to show that dose dumping is not probable.
- intermediate time point >>> to define the in vitro release profile
- final time point >>> show essentially complete release of the drug
~ During product development, it is recommended that sampling be conducted at 30min, 1h, 2h, and every 2h until complete drug release
~ 3 levels of acceptance criteria (L1, L2 & L3)
Suppose time points of an ER product are 1, 4, and 8 h.
L1 : acceptance criteria for each individual tablet (6 unit)
- 1 hr: amount dissolved 14-34%
- 4 hr: amount dissolved 46-66%
- 8 hr: NLT 80 %
L2 : If L1 not achieved, additional 6 unit dissolution to be done -
Acceptance criteria for 12 units:
1. Avg. NLT 80% in 8 hr
2. None of 12 units is >10 % of the labeled content outside each of the stated range.
3. None of 12 units is >10 % of the labeled content below the stated amount in final test time.
Example:
1 hr:
Avg.: 14-34%
Individual: 4-44%
4hr:
Avg.: 46-66%
Individual: 36-76%
8hr:
Avg.: NLT 80 %
Individual: NLT 70 %
L3: If L2 not achieved, additional 12 unit dissolution to be done
Acceptance criteria for 24 units:
1. Avg. NLT 80% in 8 hr
2. 2. NMT 2 units are >10% of labeled content outside each of the stated ranges.
3. NMT 2 units are >10% of the labeled content below the stated amount at the final test time.
4. None is >20% of the labeled content outside each of the stated ranges.
5. None is >20% of the labeled content below the stated amount at the final test time.
Example:
1 hr:
Avg.: 14-34%
Individual: NMT 2 units are outside 4-44% & None is outside 0-54%
4hr:
Avg.: 46-66%
Individual: NMT 2 units are outside 36-76% & None is outside 26-86%
8hr:
Avg.: NLT 80 %
Individual: NMT 2 units release <70% & None release <60%
