Optimization and evaluation of resveratrol amorphous solid dispersions with a novel polymeric system

The preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, a single polymer often does not bring significantly enhance the solubility or amorphous stability of a poorly water-soluble drug. We found an application of a unique and novel binary polymeric blend in the preparation of solid dispersions. The main purpose of this study is to optimize and evaluate resveratrol (Res) amorphous solid dispersions with a novel polymeric system of poly (vinyl pyrrolidone) (PVP) and carboxymethyl chitosan (CMCS).

The influence of three different release factors, the ratio of CMCS to the polymer mixture (CMCS% = X₁), the ratio of Res to the polymer mixture (Res% = X₂) and the surfactant (Tween 80 = X₃), on the characteristics of released Res at various times (Q₅ and Q₃₀) was investigated. The computer optimization and contour plots were used to predict the levels of the independent variables as X₁ = 0.17, X₂ = 0.10 and X₃ = 2.94 for maximized responses of Q₅ and Q₃₀. Fourier transform infrared spectroscopy (FTIR) results revealed that each polymer formed hydrogen bonds with Res. The solid performance and physical stability of the optimized ternary dispersions were studied with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), modulated differential scanning calorimetry (MDSC) and dissolution testing. SEM, XRD and MDSC analysis demonstrated that the Res was amorphous, and MDSC showed no evidence of phase separation during storage.

Dissolution testing indicated a more than fourfold increase in the apparent solubility of the optimized ternary dispersions, which maintained high solubility after 90 days. In our research, we used CMCS as a new carrier in combination with PVP, which not only improved the in vitro dissolution of Res but also had better stability.

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About this article: Gangqi Han, Bing Wang, Mengli Jia, Shuxin Ding, Wenxuan Qiu, Yuxuan Mi, Zhimei Mi, Yuhao Qin, Wenxing Zhu, Xinli Liu, Wei Li. Optimization and evaluation of resveratrol amorphous solid dispersions with a novel polymeric system[J]. Mathematical Biosciences and Engineering, 2022, 19(8): 8019-8034. doi: 10.3934/mbe.2022375

Materials

Plasdone (poly (vinyl pyrrolidone)) PVPK29/32 was obtained from Ashland Inc. (KY, USA). Carboxymethyl chitosan (CMCS) was purchased from Qingdao Honghai Biotechnology Co., Ltd. (Qingdao, China). Prior to use, PVP and CMCS were dried in a desiccator over powdered phosphorus pentoxide for at least one week. trans-Resveratrol (99%, batch number #111535-202003) from the National Institutes for Food and Drug Control (Beijing, China) was used as a standard. Res was purchased from Hainuo Chemical Company (Shanghai, China). Tween 80 was obtained from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Copper chloride was purchased from Tianda Chemical Company (Tianjing, China). HPLC grade acetonitrile and methanol and analytical grade ethanol and methanol were obtained from Shanghai Macklin Biochemical Co. (Shanghai, China).