The effect of the composition of a fixed dose combination on bioequivalence results.

The purpose of this work was to develop a new supergeneric product Meloxicam/Omeprazole. Such a combination brings a benefit in terms of decreasing side effects for the patients using meloxicam. The new combination is composed of a meloxicam powder blend (MPB) and omeprazole gastro-resistant pellets (OAP) in hard gelatin capsules. The main tasks were to select the excipients to keep the functional layer of OAP active and to prove the bioequivalence to the original products of meloxicam tablets together with omeprazole capsules. Although dissolution profiles similar to the original product were obtained, the unexpected results of omeprazole low bioavailability in the fed bioequivalence study (BES I) showed the necessity to investigate the formulation in greater depth. A modified more complex dissolution method was developed in order to understand the release of omeprazole under gastric conditions. This method revealed the degradation of omeprazole in the formulation when exposed to the fed conditions because of the increase in microenvironmental pH in the capsule caused by trisodium citrate, commonly used for improving solubility of meloxicam. This pH increase dissolved the gastro-resistant layer of OAP and caused the chemical degradation. To prevent this effect, a trisodium citrate-free formulation was developed. Reformulated capsules passed the repeated fed bioequivalence study (BES II).

Cytotoxicity and induction of apoptosis by 4-amino-3-acetylquinoline in murine leukemia cell line L1210.

Nitrogen heterocyclic compounds are used in the pharmaceutical industry, in medicine and in agriculture for their biological activity. 4-Amino-3-acetylquinoline, a new synthetically prepared quinoline derivative, was the most effective compound in our primary cytotoxic screening. In this study, we evaluated cytotoxic/antiproliferative activity of quinoline using murine leukemia cell line L1210. Its ability to induce apoptosis was studied, too. Quinoline derivative acted cytotoxically on tumor cell line L1210, the IC(100) value were 50 microg/ml (for 24 h), 25 microg/ml (for 48 h) and 10 microg/ml (for 72 h). The IC(50) values was found to be less than 4 microg/ml, a limit put forward by the National Cancer Institute (NCI) for classification of he compound as a potential anticancer drug. The cytotoxic concentrations of 4-amino-3-acetyl quinoline induced morphological changes of L1210 cells and the apoptotic DNA fragmentation.