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%