Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization

• Published in: Materials Science & Engineering C 2021-05, Vol.124, p.112063-112063, Article 112063
• Main Authors: Fang, Rongzhen, Liu, Yan, Ma, Lei, Yu, Xiang, Jin, Yiguang
• Format: Article
• Language: English
• Subjects: Aqueous solutions; Artesunate; Aspirin; Bifonazole; Bioavailability; Calorimetry; Calorimetry, Differential Scanning; Curcumin; Differential scanning calorimetry; Dispersions; Dissolution; Drugs; Electron paramagnetic resonance; Electron spin; Electron spin resonance; Evaporation; Fluconazole; Fourier transforms; Free radical; Free radical polymerization; Free radicals; Genistein; Hydrogen bonding; Ibuprofen; Indomethacin; Infrared spectra; Ketoconazole; Materials science; Miconazole; N-vinyl-2-pyrrolidone; Nonsteroidal anti-inflammatory drugs; Olanzapine; Pharmaceutical Preparations; Photocuring; Photopolymerization; Polyvinylpyrrolidone; Pyrrolidinones; Quercetin; Resveratrol; Scavenging; Solid dispersion; Solubility; Spectrometry; Spectroscopy, Fourier Transform Infrared; Spin resonance; Sulfamethoxazole; X-Ray Diffraction
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2021.112063

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields. [Display omitted] •N-vinyl-2-pyrrolidone (NVP) photopolymerization is used for facile preparation of drug solid dispersions.•The scanvenging free radical property of drugs prevents the formation of NVP-based solid dispersions.•The molecularly miscible state of drugs in NVP-based solid dispersions improves the dissolution of drugs with controlled behavior.