Microemulsion Formulation Development and Evaluation for Parenteral Administration of Filgrastim
Project no. 21540 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
Neutropenia: Absolute Neutrophil Count (ANC) is below 1000/mm³. If the neutrophil count is below 500/mm³, it is called severe neutropenia, and below 200/mm³ it is called very severe neutropenia [1] . Neutropenia: It may occur due to gene mutations, production of antibodies against neutrophils in the womb, being seen as a side effect with the use of certain drugs such as chemotherapeutics, autoimmune response, a past infection, or idiopathic. Granulocyte colony stimulating factor (G-CSF); is a cytokine that stimulates the differentiation and proliferation of neutrophil precursors in the bone marrow. G-CSF is often administered prophylactically in patients at increased risk of long-term severe neutropenia after cytotoxic chemotherapy. In addition, it is used clinically to reduce the duration and frequency of neutropenia in patients diagnosed with neutropenia [1] . Filgrastim is a G-CSF analog and is produced in recombinant Escherichia coli bacteria culture, which generally contains the gene encoding the G-CSF protein. Within the scope of this thesis, in this study, it is aimed to develop a microemulsion formulation for parenteral administration that is more stable than the filgrastim formulation on the market, without changing the biological activity and extended shelf life. In this study, first, microemulsion formulations with oil phase, different surfactants and co-surfactants were developed, and the suitable formulation was determined by characterizing the developed formulations. Cytotoxicity tests (on L-929 cells), biological activity studies and stability studies were performed in selected formulations. The biological activity of the developed filgrastim formulation; was investigated in mouse NFS-60 cells and compared with the commercially available filgrastim preparation. Obtained results are presented by statistical analysis. As a result, thesis work; The development of a new, untested microemulsion formulation for filgrastim and the effect of the developed microemulsion system on bioactivity were evaluated in vitro in cell lines. The methods optimized by the thesis study can act as a steppingstone for further studies. As a result of the hypotheses realized, preliminary data are presented for a stabil formulation of filgrastim for use in neutropenia.