College of Veterinary Medicine, Gansu Agricultural University, Anning District, Lanzhou 730070, China.
Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Qilihe District, Lanzhou 730050, China.
Int J Mol Sci. 2024 Oct 1;25(19):10591. doi: 10.3390/ijms251910591.
Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A hydrophilic polymer was selected as the carrier, and a solid dispersion was prepared using a medium grinding method, with samples characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and particle size distribution (PSD). To maximize CTC solubility and stability, different polymer types and optimal drug-to-polymer ratios were screened. The solubility of optimized povidone K30 (PVPK30) (1/0.75, /)-, hydroxypropyl-β-cyclodextrin (HP-β-CD) (1/2, /)-, and gelatin (1/1, /)-based solid dispersions was 6.25-, 7.7-, and 3.75-fold higher than that of pure CTC powder, respectively. Additionally, in vitro dissolution studies showed that the gelatin-based solid dispersion had a higher initial dissolution rate. SEM and PS analyses confirmed that this dispersion had smaller and more uniform particles than PVPK30 and HP-β-CD dispersions. Therefore, successful solid polymer dispersion preparations improved the CTC solubility, dissolution rates, and stability, which may have potential as drug delivery systems.
盐酸金霉素(CTC)是一种广谱四环素类抗生素,具有广泛的抗菌活性。由于溶解度低、稳定性差、生物利用度低,其临床制剂的开发受到限制。我们试图通过制备固体分散体来提高其溶解度和溶解速率。选择亲水性聚合物作为载体,采用中磨法制备固体分散体,采用扫描电子显微镜(SEM)、差示扫描量热法(DSC)、热重分析(TGA)、粉末 X 射线衍射(PXRD)、傅里叶变换红外光谱(FT-IR)和粒径分布(PSD)对样品进行表征。为了最大限度地提高 CTC 的溶解度和稳定性,筛选了不同的聚合物类型和最佳的药物-聚合物比例。优化的聚乙烯吡咯烷酮 K30(PVPK30)(1/0.75,/)-、羟丙基-β-环糊精(HP-β-CD)(1/2,/)-和明胶(1/1,/)-基于固体分散体的溶解度分别比纯 CTC 粉末高 6.25、7.7 和 3.75 倍。此外,体外溶解研究表明,基于明胶的固体分散体具有更高的初始溶解速率。SEM 和 PS 分析证实,该分散体的颗粒比 PVPK30 和 HP-β-CD 分散体更小且更均匀。因此,成功的固体聚合物分散体制备提高了 CTC 的溶解度、溶解速率和稳定性,这可能作为药物传递系统具有潜力。