Standard Deliberation

Investigation on evaluation method of in vitro release test for Kushen ointment

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  • 1. Shanghai Institute for Food and Drug Control, NMPA Key Laboratory for Quality Analysis of Chemical Drug Preparations, Shanghai 201203, China;
    2. Shanghai Baolong Pharmaceutical Co., Ltd, Shanghai 201707, China;
    3. Shanghai University of Medicine & Health Sciences, Shanghai 201318, China

Received date: 2022-08-29

  Online published: 2024-06-24

Abstract

Objective: To develop an evaluation method of in vitro release test for Kushen ointment and investigate the consistency of release behavior in pre-and post-manufacturing change of Kushen ointment. Methods: The modified Franz diffusion cell was employed for the in vitro release test of ointments. The dissolution was determined by HPLC method based on the test of Kushen ointment in Chinese Pharmacopoeia (2020 edition). The consistency of release behavior of Kushen ointment varied with the formulation and preparation process was evaluated. The released drug substances included four active ingredients oxymatrine, sophoridine, matrine and sophocarpine. Chromatographic separation was performed on a Shim-pack GIS C18 (100 mm×4.6 mm, 5 μm) column using a mobile phase of acetonitrile (A) and 0.1% phosphoric acid solution (adjusted to pH 8.0 with triethylamine) (B) with a gradient elution. The detection wavelength was 210 nm, the column temperature was 35 ℃, the injection volume was 100 μL, and the flow rate was 2.0 mL·min-1. Results: All 6 batches of Kushen ointment samples were completely released at 18 h and the released amount were more than 85%. The in vitro release rate of 3 batches of Kushen ointment samples in pre-manufacturing change were 4 058.9, 4 137.8 and 3 873.6 μg·cm-2·h-1/2, respectively. The in vitro release rate of 3 batches of Kushen ointment samples in post-manufacturing change were 4 177.9, 4 333.9 and 4 389.1 μg·cm-2·h-1/2, respectively. The 90% confidence interval of the in vitro release rate of Kushen ointment samples in pre-and post-manufacturing change was 89.80%-102.94% within the quality consistency range from 75% to 133.33% defined by the FDA guideline. The cumulative release curve similarity factor f2 between pre- and post-manufacturing change of Kushen ointment was 69.9 within the range from 50 to 100. Conclusion: The release behavior of Kushen ointment variation with the formulation and preparation process was demonstrated to be quality consistent through the evaluation method of in vitro release test for Kushen ointment and met the requirements.

Cite this article

LING Xia, YE Xiao-xia, ZHANG Tao, FANG Jing-wen, LE Jian . Investigation on evaluation method of in vitro release test for Kushen ointment[J]. Chinese Journal of Pharmaceutical Analysis, 2023 , 43(8) : 1408 -1417 . DOI: 10.16155/j.0254-1793.2023.08.17

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