No abstract

This paper describes the evaluation of the in vitro equivalence of capsules containing a BCS Class II compound, ketoprofen, marketed in Russia under biowaiver conditions and the innovator product. The in vitro equivalence test was carried out according to WHO Technical Report Series, No. 937, Annex 8. Dissolution profiles of test and reference (innovator) ketoprofen capsules are considered equivalent at pH 6.8 without statistical treatment, equivalent at pH 4.5 (f 1 = 3 and f 2 = 80), and not equivalent at pH 1.2 (f 1 = 22 and f 2 = 41). Generally, the evaluated capsules did not meet biowaiver criteria for drugs containing BCS Class II API, possibly due to the effect of surfactant (sodium lauryl sulfate) contained in the test preparation on the solubility.

The current paper is devoted to in vitro dissolution kinetics studies of amlodipine tablets marketed in Russia under biowaiver conditions. Dissolution kinetics studies were carried out according to WHO Guidance. Dissolution profiles of test and reference (innovator) amlodipine tablets were considered equivalent.

Adaptation to transauricular electrostimulation decreases the content of epinephrine in the adrenal glands and norepinephrine in the heart, hnmobilization stress has no appreciable effect on the content of catecholamines in the heart and adrenal glands. In animals with myocardial inl~arction, the content of norepinephrine in the hem"~ decreases 2-fold, while the content of epinephrine in the adrenals decreases inconsiderably. Adaptation to transauricular electrostimulation is associated with a rise in met-enkephalin concentration. Preadaptation induces a more pronounced rise of met-enkephalin and promotes normalization of epinephrine hi the adrenals, without changing the content of norepinephrine in the hem~.

One way of establishing the interchangeability of generic drugs is based on an in vitro study of the dissolution kinetics (biowaiver). The most common approaches for assessing the ability to use the biowaiver procedure instead of the traditional bioequivalence evaluation for generics are reviewed.