RESUMO
BACKGROUND: The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the original manufacturer's packaging. OBJECTIVES: This study aimed to assess the physical and chemical stability of clozapine tablets for up to 84 days after repackaging. METHODS: A total of 900 tablets of clozapine 100 mg (Viatris) were repackaged and stored under five different conditions to conduct physical and chemical stability tests on days 0, 28, 56 and 84. The results were compared with control tablets in their original packaging. Visual inspections of tablet appearance were performed. Physical tests included assessments of mass uniformity, friability and resistance to crushing, following the standards of the European Pharmacopoeia 11th edition. The chemical stability was determined using ultra-high performance liquid chromatography with tandem-mass spectrometry detection (UHPLC-MS/MS) to measure clozapine concentration, N-desmethyl-clozapine, and monitor clozapine degradation to detect formation of any degradation products other than N-desmethyl-clozapine. RESULTS: Visual examination showed changes in the appearance of tablets only in those stored under UV light. Mass uniformity met standards for all tablets over 84 days. None passed the friability test due to tablet cracking after tumbling. A gradual deterioration in tablet hardness was observed with the resistance to crushing test. In terms of chemical stability, N-desmethyl-clozapine was undetected in any of the tablets stored under all conditions, and the mean concentration of clozapine remained within the target range over 84 days. CONCLUSION: N-desmethyl-clozapine was not detected and clozapine concentrations remained stable under all storage conditions. The tablets were compliant with the mass uniformity test in each condition. However, the tablets were cracked in the friability test and gradual deterioration in tablet hardness was observed. In the light of these results, the Vinatier Hospital pharmacy has chosen to establish a shelf life for clozapine tablets of 84 days.
RESUMO
Adipose-derived mesenchymal stem cells (ASCs) are well known for their secretory potential, which confers them useful properties in cell therapy. Nevertheless, this therapeutic potential is reduced after transplantation due to their short survival in the human body and their migration property. This study proposes a method to protect cells during and after injection by encapsulation in microparticles of calcium alginate. Besides, the consequences of encapsulation on ASC proliferation, pluripotential, and secretome were studied. Spherical particles with a mean diameter of 500 µm could be obtained in a reproducible manner with a viability of 70% after 16 days in vitro. Moreover, encapsulation did not alter the proliferative properties of ASCs upon return to culture nor their differentiation potential in adipocytes, chondrocytes, and osteocytes. Concerning their secretome, encapsulated ASCs consistently produced greater amounts of interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared to monolayer cultures. Encapsulation therefore appears to enrich the secretome with transforming growth factor ß1 (TGF-ß1) and macrophage inflammatory protein-1ß (MIP-1ß) not detectable in monolayer cultures. Alginate microparticles seem sufficiently porous to allow diffusion of the cytokines of interest. With all these cytokines playing an important role in wound healing, it appears relevant to investigate the impact of using encapsulated ASCs on the wound healing process.
