Safety Monitoring

Reseach on methods for in vitro determination of the tissue residues of nasal thermosensitive gel

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  • 1. Laboratory of Biologicals and Biomaterials, College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China;
    2. Department of Pharmacy, the Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Jinhua 322023, China;
    3. Zhejiang Provincial Key Laboratory & Collaborative Innovation Center for Quantum Precision Measurement, Hangzhou 310023, China

Received date: 2020-10-22

  Online published: 2024-06-24

Abstract

Objective: To improve the flushing device for tissue residual method and to establish a more suitable method for the determination of tissue adhesion of nasal mucosal delivery gel preparations. Methods: According to the rheological properties of nasal mucus,a suitable simulated nasal mucus was selected as the mucosal flushing fluid,and the simulated nasal mucus was rinsed at a flow rate of 1.0 mL·min-1 to carry out the tissue residual test. A self-made flushing device was designed and compared with the dissolution apparatus. And the precision of gel quantification was compared between weighing method and fluorescence tracer method. Results: To simulate the nasal mucosa with fresh egg shell membrane, under the same condition as the real nasal mucus solids, comparing the change trend of the shear rate and viscosity of various simulated mucus, it was found that the hydroxyethyl cellulose(HEC)-lysozyme solution had the properties of shear thinning, but the viscosity was about 20 mPa·s higher than that of real nasal mucus, and the solution was unstable, with a large amount of flocculent precipitation appeared after long-term storage. The viscosity of the mucin-lysozyme (1% each) solution and the HEC-gelatin (1% each) solution were close to about 13 mPa·s, which was consistent with the viscosity of healthy human nasal mucus. However, only the HEC-gelatin solution was stable without precipitation after being stored for a long time, and the fluorescence intensity of the solution was stable during the measurement period (21-22 a.u.), and had the rheological properties most similar to healthy human nasal mucus, which met the test requirements. In the method of determining the amount of tissue residue, the fluorescence probe method using fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) as a probe resulted in a quantitative RSD value between 5% and 10%,which was not only smaller than the result of weighing method, but also met the requirements of the Chinese Pharmacopoeia. When using the experimental self-made device for flushing and fluorescence tracing method, the RSD value in the group was between 5% and 10%, and the repeatability was good. Conclusion: Using a self-made flushing device and hydroxyethyl cellulose gelatin solution as a mucosal rinsing fluid,the tissue residue of thermosensitive gel in nasal mucosa delivery process was quantitatively determined by fluorescence tracing. This method is simple and reliable.

Cite this article

XIU Xue-liang, FU Shu-ting, LIU Yong, LI Zhi-yong, MA Feng-sen . Reseach on methods for in vitro determination of the tissue residues of nasal thermosensitive gel[J]. Chinese Journal of Pharmaceutical Analysis, 2021 , 41(11) : 2007 -2016 . DOI: 10.16155/j.0254-1793.2021.11.19

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