Formulation Development of Doxycycline-Loaded Lipid Nanocarriers using Microfluidics by QbD Approach
Journal
Journal of pharmaceutical sciences
Date Issued
2023
Author(s)
Lee, Chia Ying
Tsai, Tsuimin
Hsieh, Chien-Ming
Huang, Jeng-Wen
Abstract
Liposomes have been used to improve therapeutic efficacy of drugs by increasing their bioavailability and altering biodistribution. The loading capacity of small molecules in liposomes remains a critical issue. Besides, the manufacturing process of liposomes requires multi-step procedures which hinders the clinical development. In this study, we developed a promising lipid-based nanocarriers (LN) delivery system for hydrophilic charged compounds using doxycycline (Doxy) as a model drug. This Doxy-loaded lipid nanocarrier (LN-Doxy) was fabricated by microfluidic technology. Design of experiments (DoE) was constructed to outline the interactions among the critical attributes of formulation, the parameters of microfluidic systems and excipient compositions. Response surface methodology (RSM) was furthered used for the optimization of LN-Doxy formulation. The LN-Doxy developed in this study showed high drug to lipid ratio and uniform distribution of particle size. Compared to Doxy solution, this LN-Doxy has reduced in vitro cellular toxicity and significant therapeutic efficacy which was verified in a peritonitis animal model. These results show the feasibility of using microfluidic technology combined with QbD approach to develop the LN formulation with high loading efficiency for ionizable hydrophilic drugs.
Subjects
Design of experiment; Doxycycline; Lipid-based nanocarrier; Microfluidics
Type
journal article