TY  - JOUR
A1  - Blume, Henning
A1  - Weitschies, Werner
T1  - Medicinal products with pH-dependent solubility - a problem for BA/BE assessment?
T2  - European journal of pharmaceutical sciences
N2  - The ICH M13A draft bioequivalence guideline allows the exclusion of very low plasma profiles from the statistical evaluation in exceptional cases, i.e., if such phenomenon occurs due to non-compliance of subjects (not swallowing the product). Moreover, the draft ICH guideline requests additional bioequivalence studies for medicinal products with pH-dependent solubility after concomitant administration of gastric pH modifying preparations, e.g., proton pump inhibitors. Both regulations are scientifically sound, however, would need further specification. Main problem in this context is that compounds with very low solubility and slow intrinsic dissolution in the intestinal environment will cause significant bioavailability problems if their solid oral dosage forms are emptied from the stomach undisintegrated. Also very low plasma profiles may result under these circumstances. Such cases can occur accidentally and are not resultant of non-compliance. Thus, limitation for one case per study only as suggested in the guideline is not justified.
KW  - ICH M13A draft guideline
KW  - bioequivalence
KW  - exclusion of very low profiles
KW  - pH-dependent solubility
KW  - rapid gastric emptying
Y1  - 2024
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83532
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-835327
SN  - 0928-0987
VL  - 2024
IS  - 106756, In Press, Journal Pre-proof
PB  - Elsevier
CY  - Amsterdam
ER  -