Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.
Muhammad InamLu LiuJian-Wei WangKa-Xi YuChi-Uyen PhanJie ShenWen-Hua ZhangGuping TangXiurong HuPublished in: International journal of molecular sciences (2021)
Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.
Keyphrases
- blood glucose
- magnetic resonance
- high resolution
- glycemic control
- electron microscopy
- type diabetes
- anti inflammatory
- endothelial cells
- dual energy
- ionic liquid
- computed tomography
- induced apoptosis
- cardiovascular disease
- high throughput
- early stage
- magnetic resonance imaging
- blood pressure
- adipose tissue
- signaling pathway
- endoplasmic reticulum stress
- weight loss
- insulin resistance
- pet ct
- case control
- replacement therapy
- image quality
- pluripotent stem cells