Insight into the Phase Transformation among Various Solid Forms of Baicalein

A new polymorph and three hydrates of baicalein, a widely prescribed anti-inflammatory TCM drug, were discovered through comprehensive polymorph screening experiments. The forms were fully characterized by a range of analytical techniques, including PXRD, Raman spectra, FTIR, HSM, SEM, TGA, DSC, and DVS. Single crystal structures and the transformation pathways among different polymorphs and hydrates are discussed in detail. Single-crystal-to-single-crystal transformation behavior between monohydrate and hemihydrate was revealed. Thermodynamic stability, hygroscopicity, and powder dissolution behavior were investigated. The results show that the newly discovered form γ presents better dissolution behavior and remarkably greater apparent solubility compared with the current widely used marketed drug substance

Insight into the Phase Transformation among Various Solid Forms of Baicalein

A new polymorph and three hydrates of baicalein, a widely prescribed anti-inflammatory TCM drug, were discovered through comprehensive polymorph screening experiments. The forms were fully characterized by a range of analytical techniques, including PXRD, Raman spectra, FTIR, HSM, SEM, TGA, DSC, and DVS. Single crystal structures and the transformation pathways among different polymorphs and hydrates are discussed in detail. Single-crystal-to-single-crystal transformation behavior between monohydrate and hemihydrate was revealed. Thermodynamic stability, hygroscopicity, and powder dissolution behavior were investigated. The results show that the newly discovered form γ presents better dissolution behavior and remarkably greater apparent solubility compared with the current widely used marketed drug substance

Insight into the Phase Transformation among Various Solid Forms of Baicalein

A new polymorph and three hydrates of baicalein, a widely prescribed anti-inflammatory TCM drug, were discovered through comprehensive polymorph screening experiments. The forms were fully characterized by a range of analytical techniques, including PXRD, Raman spectra, FTIR, HSM, SEM, TGA, DSC, and DVS. Single crystal structures and the transformation pathways among different polymorphs and hydrates are discussed in detail. Single-crystal-to-single-crystal transformation behavior between monohydrate and hemihydrate was revealed. Thermodynamic stability, hygroscopicity, and powder dissolution behavior were investigated. The results show that the newly discovered form γ presents better dissolution behavior and remarkably greater apparent solubility compared with the current widely used marketed drug substance

Highly Crystalline Forms of Valsartan with Superior Physicochemical Stability

Single crystal structures of blockbuster antihypertensive drug Valsartan are revealed the first time in this report. Two new highly crystalline forms, named form E and an ethanol solvate form F, were discovered and fully characterized by PXRD, Raman, IR, TG, DSC, and DVS. Conformational flexibility and single crystal structures are discussed in detail. Physicochemical properties, such as hygroscopicity, chemical stability, crystallinity, and dissolution behaviors, are compared with the marketed solid-state form (amorphous state). The results show that the newly discovered highly crystalline form E presents a remarkably different dissolution behavior and superior chemical stability

Improving Dissolution and Photostability of Vitamin K3 via Cocrystallization with Naphthoic Acids and Sulfamerazine

Menadione (MD), also known as vitamin K3, has been widely applied in fortified food, feed, and the nutrition industry for its antihemorrhagic activity. However, the poor photostability in the solid state has greatly affected its biological performance and limited its applications. With the objective to alter the topochemical photoreactivity, a cocrystallization approach was employed, and three MD cocrystals with naphthoic acids and sulfamerazine were designed and prepared. Single crystal structures were determined, and solid-state characterization were performed. Solid-state UV–vis spectra revealed a significant red-shift of UV absorption in the cocrystal solids resulting in variant color differences. These physicochemical changes may be attributed to the enhanced π···π interactions and change-transfer interactions within these molecular complexes. More importantly, the newly synthesized cocrystals displayed better dissolution behavior and superior photostability with respect to MD itself. No obvious degradation was observed under stressed photoirradiation conditions. These findings may provide new possibilities to the application of this key vitamin

Highly Crystalline Forms of Valsartan with Superior Physicochemical Stability

Single crystal structures of blockbuster antihypertensive drug Valsartan are revealed the first time in this report. Two new highly crystalline forms, named form E and an ethanol solvate form F, were discovered and fully characterized by PXRD, Raman, IR, TG, DSC, and DVS. Conformational flexibility and single crystal structures are discussed in detail. Physicochemical properties, such as hygroscopicity, chemical stability, crystallinity, and dissolution behaviors, are compared with the marketed solid-state form (amorphous state). The results show that the newly discovered highly crystalline form E presents a remarkably different dissolution behavior and superior chemical stability

Polymorphs and Hydrates of Apatinib Mesylate: Insight into the Crystal Structures, Properties, and Phase Transformations

Apatinib mesylate (ATM) is an orally administrated anticancer agent for the treatment of advanced gastric cancer. Single-crystal structures of four ATM solid forms, including two anhydrous polymorphs (I and II) and hydrates (HA and HB), were elucidated by single-crystal X-ray diffraction. The properties of these various forms were fully characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform-infrared spectroscopy, and Raman spectroscopy. The discrepant molecule conformations, H-bonding interactions, and packing arrangements in the crystal structures were analyzed associated with the hygroscopicity of forms I and II. Various form transformations induced by either moisture or solution conditions were examined, and the relative stability was established. The results revealed that HA is the most thermodynamically stable form and is superior to the currently marketed form

Cocrystals of Baicalein with Higher Solubility and Enhanced Bioavailability

Baicalein (<b>Bai</b>) is one of the most important bioactive flavonoids isolated from the well-known traditional Chinese medicine called “Huang Qin”. Though it has broad therapeutic capability, the bioavailability is limited due to its poor solubility. In this study, we aimed to modulate its solubility through cocrystallization. Cocrystals of <b>Bai</b> with isoniazide (<b>Inia</b>), isonicotinamide (<b>Inam</b>), caffeine (<b>Caf</b>), and theophylline (<b>Tph</b>) were obtained. And different cocrystallization methods lead to different cocrystal phases for <b>Inam</b> and <b>Tph</b>. These cocrystals were characterized using powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, dynamic vapor sorption, and Fourier transform infrared spectroscopy. Among all the cocrystals studied, <b>BaiCaf</b> is found to be superior in powder dissolution and pharmacokinetic behavior. Area under the curve values of <b>BaiCaf</b> is improved by a factor of 4.1, and the bioavailability of baicalein is thus expected to be accordingly increased. Given that <b>Caf</b> is a central nervous system stimulant available in many prescription and nonprescription medications, <b>BaiCaf</b> can be a promising alternative solid form of <b>Bai</b> to be developed

Zwitterionic Cocrystals of Flavonoids and Proline: Solid-State Characterization, Pharmaceutical Properties, and Pharmacokinetic Performance

We utilized the concepts of crystal engineering to acquire cocrystals of d/l-proline with a variety of flavonoids and further evaluated the impact on solubility and pharmacokinetic of flavonoids. We have synthesized and characterized six d/l-proline cocrystals with flavonoids and their single crystal structures were revealed. The powder dissolution profiles were determined and the pharmacokinetic properties for Kae-l-Pro were analyzed and compared with the corresponding physical mixture. d/l-Proline was found to be a suitable coformer for a variety of structural similar flavonoids. This study may offer an alternative approach for the development of these widely used flavonoids

Modulating the Dissolution and Mechanical Properties of Resveratrol by Cocrystallization

Resveratrol (RSV), a dietary polyphenol found in red wine, has renewed interest in recent years due to a broad range of in vitro evidence that indicate cardioprotective effects. Herein, we have synthesized four RSV cocrystals with the objective to improve the physicochemical and mechanical properties. Single crystal structures were illustrated and comprehensive characterization of the cocrystals were performed. In addition, powder dissolution of RSV cocrystals in different buffer medium containing different surfactants were conducted, and the result revealed that PVP K30 is an effective surfactant to maintain the supersaturation. Then pharmacokinetic experiments suggested that RSV cocrystals showed shorter <i>T</i>_max, and RSV–NA exhibited higher <i>C</i>_max and AUC_0–24 values. Furthermore, RSV cocrystals exhibited superior mechanical properties compared to RSV pure component. These results may provide an alternative formulation for RSV