Bioequivalence and Bioavailability Forum

Dear HS,

❝ Did FDA publish a product-specific guidance? In vitro testing for alcohol induced dose dumping is not a general requirement – only in specific cases (like Oxycodone ER).

Yes they have published.. same sentence "Please conduct comparative dissolution testing on 12 dosage units each of all strengths of the test and reference products.Specifications will be determined upon review of the application" is also repeated .

❝ In the first sentence you said f₂ ‘is matching in all the required dissolution mediums’. Do you mean: passing f₂ in conventional media and failing in testing alcohol induced dose dumping?

Exactly thats what i meant.

❝ Only as a last resort (throwing away the successful BE study). Hypromellose is much less susceptible to alcohol than methacrylic acid / ethyl acrylate copolymer.

that would be difficult and painful after investing so much efforts (also the money).

I am pasting the data here if it helps.
0.1N HCl with 40% alcohol, USP-I with sinker, 100RPM, 900mL.
  TIME  AVG%  AVG%(Innovator)  Difference
 15 MIN  15      6                9
 30 MIN  23     11               13
 45 MIN  30     14               16
 60 MIN  36     18               18
 75 MIN  42     21               21
 90 MIN  48     23               25
105 MIN  53     26               27
120 MIN  58     28               30

F2=33

P.S. Hope to meet u soon @Mumbai.

Regards

Chiku:)