Dissolution testing should be carried out in USP Apparatus I at 100 rpm or Apparatus II at 50 rpm using 900 mL of the following dissolution media: (i) 0.1 N HCl or simulated gastric fluid USP without enzymes, (ii) a pH 4.5 buffer, and (iii) a pH 6.8 buffer or simulated intestinal fluid USP without enzymes. For capsules and tablets with gelatin coating, simulated gastric and intestinal fluids USP (with enzymes) can be used.
Dissolution testing apparatus used in this evaluation should conform to the requirements in USP (< 711 > dissolution). Selection of the dissolution testing apparatus (USP Apparatus I or II) during drug development should be based on a comparison of in vitro dissolution and in vivo pharmacokinetic data available for the product. The USP Apparatus I (basket method) is generally preferred for capsules and products that tend to float, and USP Apparatus II (paddle method) is generally preferred for tablets. For some tablet dosage forms, in vitro (but not in vivo) dissolution may be slow due to the manner in which the disintegrated product settles at the bottom of a dissolution vessel. In such situations, USP Apparatus I may be preferred over Apparatus II. If the testing conditions need to be modified to better reflect rapid in vivo dissolution (e.g., use of a different rotating speed), such modifications can be justified by comparing in vitro dissolution with in vivo absorption data (e.g., a relative BA study using a simple aqueous solution as the reference product).
A minimum of 12 dosage units of a drug product should be evaluated to support a biowaiver request. Samples should be collected at a sufficient number of intervals to characterize the dissolution profile of the drug product (e.g., 10,15, 20, and 30 minutes).
When comparing the test and reference products, dissolution profiles should be compared using a similarity factor (f2). The similarity factor is a logarithmic reciprocal square root transformation of the sum of squared error and is a measurement of the similarity in the percentage of dissolution between the two curves.
Two dissolution profiles are considered similar when the f2 value is > 50. To allow the use of mean data, the coefficient of variation should not be more than 20% at the earlier time points (e.g., 10 minutes), and should not be more than 10% at other time points. Note that when both the test and reference products dissolve 85% or more of the labeled amount of the drug in < 15 minutes using all three dissolution media recommended above, the profile comparison with an f2 test is unnecessary.
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