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DISSOLUTION
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After approximately a century of development, the relevance of dissolution testing is indisputable.
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Figure 1. Dissolution profi les in USP 34 conditions (apparatus 2, paddle, 900 ml of 1% Sodium Lauryl Sulfate, 75 rpm) of four brands of 200 mg CBZ tablets.
products to healthy volunteers and measuring the drug levels in saliva samples of the volunteers [13, 14].
When establishing a correlation between the in vivo and in vitro results obtained for CBZ products, it was found that:
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Products that were bioequivalent (BE) in terms of rate (the Cmax
/ABC0-t and Tmax absorbed (AUC0-t
parameters BE), but not in amount , AUC0-inf and Cmax not BE), presented in
vitro dissolution profiles that were similar according to the f factors but not in terms of their AUC or DE (products CBZ-A and CBZ-B, red lines in Figure 1).
•
Products that were BE in amount absorbed (AUC0-t and Cmax
confidence interval for the Cmax blue lines in Figure 1).
This clearly illustrates the nature of both types of comparisons. The f2
factor accounts for the differences in the percentage dissolved by measuring vertical distances, regardless of its position in the time axis, which makes this index very sensitive to the differences in the first time points (case of the CBZ-C and D products, see Figure 1). Differences in the first times sampled, that have little or no impact on the profile AUC, could have a major impact on the f2
sometimes is calculated only with a few points, as in the case of rapidly dissolving products (i.e. up to 85% before 30 minutes).
Therefore, whereas the f2 factor is mainly related to the in vivo
absorption rate, the AUC and DE parameters are predominantly related to the in vivo absorbed amount.
32 | | November/December 2013
BE), and almost in absorption rate (the 90% /ABC0-t
parameter was
78.2-122.9%), presented similar AUC and DE but did not meet the f2
similarity criteria (products CBZ-C and CBZ-D,
The results obtained for PHT illustrate another related factor: the two products tested were BE in vivo (even according to the individual bioequivalence methodology applied) but their dissolution profi les only resulted equivalent in terms of their AUC and DE (p>0.05), with a f2
<50 (Figure 2).
value, which
Figure 2. Dissolution profi les in USP 34 conditions (apparatus 1, basket, 900 ml of distilled water, 50 rpm) of two brands of 100 mg PHT capsules. The gray-shaded rectangle highlights the diff erences in the fi rst three time points detected by the f2
factor.
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