English to Russian Medical Medical: Pharmaceuticals

Physiology Based Dissolution Testing (PBDT)

The PBDT results are presented in Figure 6 and show little or no dissolution in the simulated stomach.
This is expected due to the poor solubility of simeprevir in a pH smaller than its pKa of 5.24 of its acid moiety N-cyclopropylsulfonyl carboxamide.
In the second phase of PBDT, dissolution increases up to about 60% after 2 hours in FeSSIF.
FeSSIF contains 15 mMol Na-Taurocholate, a natural surfactant present in bile, 3.75 mM lecithin to form mixed micelles, and 11.874 g/L NaCl in buffer pH 5.
In this PBDT setting using biorelevant media, no substantial difference is seen between the tested batches, in contrast to the results observed using the QC dissolution test (see Table 11).
The stability batches with a lower dissolution result at the *30 minutes Q-time point* of the QC method show similar PBDT results as for the recently manufactured commercial batches and the registration batch.
This indicates that the QC dissolution test is overly discriminating compared to PBDT.