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Furosemide (Fur) is a BCS class IV diuretic drug with low bioavailability due to its poor solubility and poor membrane permeability. Triamterene (Tri) is a potassium‐sparing diuretic with low bioavailability due to its poor solubility. Here, a novel drug–drug salt composed of Tri and Fur was successfully synthesized. Tri–Fur was comprehensively characterized with single‐crystal X‐ray and powder X‐ray diffraction techniques, thermogravimetric analysis, differential scanning calorimetry and dynamic vapor sorption. The apparent equilibrium solubility (in pH 2.0 buffer) of Tri–Fur is improved compared with Fur and a physical mixture of Tri with equimolar Fur by 15.3‐fold and 12.2‐fold enhancements, respectively. Its intrinsic dissolution rate (in pH 2.0 buffer) is also higher than for a Fur component with an enhancement of 9.5‐fold. This study provides a valuable insight into the formation of dual pharmaceutical salts and demonstrates that Tri–Fur can be a potential alternative formulation. A novel drug–drug salt of furosemide (a rapid‐acting diuretic) with triamterene (a potassium‐sparing diuretic) was successfully synthesized. This dual pharmaceutical salt was comprehensively characterized using single‐crystal/powder X‐ray diffraction, thermal analysis and vibrational spectroscopy. [ABSTRACT FROM AUTHOR]

Three isostructural cocrystals of apremilast, a novel anti-psoriasis oral agent, with nicotinamide, caffeine, and acetylsalicylic acid were successfully designed and synthesized. Both the apparent solubility and intrinsic dissolution rate of apremilast in a pH 2.0 buffer have been improved via the formation of cocrystals. [ABSTRACT FROM AUTHOR]

Co-amorphization has recently been shown to be a promising approach for stabilizing amorphous drugs and improving the dissolution rate of poorly water-soluble drugs. In this study, three basic amino acids were chosen as small molecular weight excipients to interact with the drug to form co-amorphous combinations. The co-amorphous combinations of valsartan (VAL) with l-histidine, l-arginine, and l-lysine were prepared by vibrational ball milling. Solid-state characterization with X-ray powder diffraction and differential scanning calorimetry (DSC) revealed that all of the co-amorphous mixtures were homogeneous. The molecular interactions of the co-amorphous mixtures were investigated through the glass transition temperature (Tg) in the DSC measurements and Fourier transform infrared spectroscopy. The drug remained chemically stable during the milling process, and the co-amorphous formulations were generally physically stable over at least 3 months at 40 °C under dry conditions. The dissolution rate of all of the co-amorphous mixtures was significantly increased over that of the amorphous VAL alone. The results of this study demonstrated the potential of amino acids as small molecular weight excipients in co-amorphous formulations to improve the drug solubility and dissolution rate. [ABSTRACT FROM AUTHOR]

A comprehensive solid-state screening experiment was performed for icariin (ICA), an active substance in Traditional Chinese Medicine (TCM) which has long been used to treat osteroporosis. Two new polymorphs in their pure forms and ten different solvate modifications were obtained and the single crystal structures were successfully determined. The isostructural phenomenon was readily observed among various organic solvates. Notably, the single crystal structure of the marketed hydrate form H1 was determined for the first time through a single crystal–single crystal transformation (SCSCT) process. The physicochemical properties of various solid forms were further studied. The results show that the newly discovered pure form α presents better thermal stability, lower hygroscopicity and higher solubility compared to the currently marketed form. The superior physicochemical properties render a better drug development ability for this widely applied TCM. [ABSTRACT FROM AUTHOR]

Four dapsone–flavone cocrystals were synthesized, including three polymorphic 1 : 1 cocrystals and a 1 : 2 cocrystal. Single crystal structures were disclosed, and the differences in H-bonding interactions were illustrated by comparison of the crystal structures and Hirshfeld surface analysis. The various cocrystals were fully characterized by X-ray powder diffraction, FTIR and thermal analysis. The solubilities, dissolution rates and form transformations in solution were determined. The phase transformation experiments revealed complex phase transformations among the cocrystals. Solid-state transformations among different stoichiometries were also observed in the dapsone–flavone system. [ABSTRACT FROM AUTHOR]

Abstract Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility and wettability of both the crystalline forms were determined. It was found that surfactant can significantly improve the solubility of celastrol up to more than 104 times. Tween 80 and sodium dodecyl sulfate largely improved the wettability of the 2 crystals. Form I shows better wettability than form II in all the buffer solutions with polymers and surfactants. Compared with form II, form I exhibits higher solubility in carboxymethylcellulose and polyvinylpyrrolidone media but much lower solubility in tween 80 and sodium dodecyl sulfate solutions. An investigation of wettability and solubility mechanisms was fully explored, and a hypothesis was proposed to understand the abnormal solubility differences. [ABSTRACT FROM AUTHOR]

[Display omitted] Isotretinoin is the first-line drug for treatment of severe acne. Only one polymorph was reported even though it has been launched for nearly 40 years, and its clinic application was however limited by its stability and solubility challenges. In our study, two new polymorphs of isotretinoin were discovered and fully characterized. The transformation relationships between these solid forms were fully discussed, and a visible color change during single-crystal-to-single-crystal phase transition with the conformational change was investigated. Form II is determined to be thermodynamic stable form at room temperature, but metastable form at body temperature. The results show that form II is an ideal solid state possessing both superior thermal stability (60℃, open air) and higher absorption once delivered into body. The thermal stability can be associated with the crystal structure such as torsion angle. The relative bioavailability of form II is higher than form I as expected, and the bioavailability of form II formulation is about 2 times as that of the marketed form I capsule. Therefore, form II formulation could provide an alternative for better performing isotretinoin. [ABSTRACT FROM AUTHOR]