Topical Semisolid Formulations of Hirsutenone and Accelerated Stability Assessment

• Published in: Bulletin of the Korean Chemical Society Vol. 36; no. 6; pp. 1688 - 1693
• Main Authors: Kim, Sung Rae, Jeong, Kyu Ho, Lee, Sang Gon, Kang, Jong Bu, Kim, Chae Jin, Kim, Min Young, Yoon, Kyu Hyeong, Lee, Do Ik, Joo, Seong Soo, Lee, Min Won, Lee, Sangkil, Choi, Young Wook
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag GmbH & Co. KGaA 01.06.2015; Wiley‐VCH Verlag GmbH & Co. KGaA; 대한화학회
• Subjects: Hirsutenone; Ointment; Q10 method; Shelf-life; Stability; 화학
• ISSN: 1229-5949; 0253-2964; 1229-5949
• DOI: 10.1002/bkcs.10324

Effect of various antioxidants on hirsutenone (HST)‐ointment stability under accelerated storage conditions (40 °C). To develop a topical preparation of hirsutenone (HST), a natural immunomodulator, we formulated oleaginous ointments and creams and assessed their stability in terms of shelf‐life. Ointments were prepared by mixing the molten lipid phase of white petrolatum and white beeswax with glycerin and propylene glycol, in which HST was dissolved with ascorbyl palmitate (AP), butylated hydroxyl toluene (BHT), or ethylenediaminetetraacetic acid (EDTA) as an antioxidant. Reference oil‐in‐water creams were formulated by conventional emulsification. The ointment and cream formulations were subjected to accelerated stability testing at 40 °C. At appropriate time points, test samples were dissolved in organic solvent, diluted with methanol, and filtered prior to high‐performance liquid chromatography (HPLC). The degradation of HST in cream and ointment formulations followed first‐order kinetics. The rate constants (day−1) of HST in cream and ointments were 1.71 × 10−2 and 0.67 × 10−2, respectively, revealing a 2.5‐fold greater half‐life in ointments than in creams. Although AP and BHT had no effect on chemical stabilization of ointments, EDTA enhanced the stability of HST at 40 °C. The shelf‐lives of HST formulations were estimated by the Q10 method. Assuming a Q10 value of 2, the shelf‐lives (days) of cream, ointment, and ointment with EDTA at 25 °C were 14.99, 38.23, and 44.19, respectively. At 4 °C, the shelf‐life of HST in ointment with EDTA was extended to 220 days. Even though the stability of HST was somewhat increased by the ointment formulation and further improved by adding EDTA, alternative approaches are needed to increase stabilization.