•The polymorphic behavior of acyclovir-maleic acid salt (ACV-MAL) was investigated.•The room temperature crystal structure of ACV-MAL was reported.•The two solid forms of ACV-MAL are enantiotropically related.•Polymorphism of pharmaceuticals at near room temperature range is less concerned.Acyclovir is a commonly used antiviral drug while its solubility is far from satisfied. It was reported that 1:1 acyclovir-maleic acid salt (ACV-MAL) possesses much higher maximum apparent solubility. In this contribution, a new crystal structure of ACV-MAL was solved at room temperature. This new crystal structure and previously reported structure at low temperature can transform to each other via a reversible solid phase transformation, which has been confirmed by single-crystal X-ray diffraction, solid state NMR and cycling differential scanning calorimetry tests. The phase change temperature is ca. 283–293 K (10–20 °C), which is slightly lower than room temperature (298 ± 2 K/25 ± 2 °C), but is in the range of ambient temperature. This kind of near room temperature phase transformation is less concerned and tends to be neglected. This case report reminds that more attention should be paid to the polymorphism of pharmaceuticals at such temperature range due to its fundamental and practical significance.

Pharmaceutical salts have been traditionally used in drug formulation. As a salt former, acesulfame (AH), an aliphatic calorie-free sweetener, is actively being employed. Acesulfamates of active pharmaceutical ingredients (APIs) may provide a pleasant sweet taste along with modified physicochemical properties. In this paper, four quinine (QN) salts were obtained with AH, including two 1:1 anhydrous forms (QNAH11a and QNAH11b), one monohydrate of 1:1 salt (QNAH111), and one 1:2 anhydrous forms (QNAH12). The resulting salts were fully characterized by a range of analytical methods. Crystal structures of QNAH11a, QNAH111, and QNAH12 were determined by single-crystal X-ray diffraction, and the crystal structure of QNAH11b was solved from powder X-ray diffraction data by Rietveld refinement. Ionization states for all samples were confirmed by 13C solid-state NMR spectra. The mutual transformation and thermodynamic relationships of these solid forms were revealed via slurry conversion experiments and differential scanning calorimetry measurements. Additionally, enhanced solubility was observed for each acesulfamate when compared with the pure free base. This study should further highlight the potential of AH as a pharmaceutical salt/cocrystal former.

Correction for ‘Pharmaceutical crystalline complexes of sulfamethazine with saccharin: same interaction site but different ionization states’ by Xue Fu et al., RSC Adv., 2016, 6, 26474–26478.

Sulfamethazine (SMT), a widely used antibacterial drug, can form either a 1:1 salt or a 1:1 cocrystal with saccharin (SAC), an artificial sweetener. Interestingly, the two crystalline complexes possess the same main intermolecular interaction sites, except the locations of the acidic proton are different.

A novel pharmaceutical cocrystal (THPAH12) of Theophylline (THP) was obtained with an artificial sweetener, Acesulfame (AH), in a molar ratio of 1:2. Solid state NMR spectra of the cocrystal indicate that the two AH molecules exist as keto and enol tautomers, which is further confirmed by the refined crystal structure. THPAH12 is the first keto form AH containing cocrystal. This highlights the fact that not only −OH of enol form of AH, but also the −NH–C═O group of the keto form of AH should be considered when designing new pharmaceutical cocrystals via the supramolecular synthon approach. Compared with pure THP, THPAH12 possesses enhanced solubility and hydration stability, which highlight its potential for further pharmaceutical applications.

A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

The crystal structure of a powder pharmaceutical cocrystal, theophylline–nicotinamide (1:1) crystal complex, is determined for the first time by using a combination of X-ray powder diffraction (XRPD), 1D solid state NMR, as well as density functional theory (DFT) calculations. With the aid of solid state NMR spectroscopy, a candidate structure can be determined from XRPD data by Rietveld refinement with acceptable residual variances. The structure was subjected to periodic geometry optimization, followed by NMR parameter calculations. The agreement between experimental and computed 13C and 15N NMR chemical shift values validates the refined structure as an accurate representation of the actual cocrystal structure. Intermolecular interactions existing in the cocrystal are further confirmed by the commonly used vibrational spectra. This study confirms that the straightforward synergistic approach offers a simple and credible way to solve the crystal structure of powder cocrystal samples.

5-Fluorocytosine (FC), a widely used antifungal drug, has poor physical stability under different relative humidity (RH) conditions, which may trigger serious challenges during its drug product development. In this contribution, a conjugate acid–base (CAB) cocrystal and a salt hydrate of FC were obtained with an artificial sweetener, acesulfame (AH), in molar ratios of 2:1 (FCAH21) and 1:1 (FCAH11), respectively. The resulting products were characterized by a variety of analytical methods, including single-crystal and powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and dynamic vapor sorption (DVS). 13C and 15N solid-state NMR spectra provide solid evidence for the CAB cocrystal/salt formation. At room temperature, moisture sorption data show that the new forms are nonhygroscopic/slightly hygroscopic and resistant to FC hydrate formation under high RH conditions (>80%). FCAH21 has a higher FC content and presents more favorable thermal stability than FCAH11, which make it more attractive for further pharmaceutical application.

Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the quality of MRI-based diagnosis. In this work, we developed a positive T1 MRI CA based on graphene oxide (GO)–gadolinium (Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO, followed by Gd(III) complexation, to form a T1 MRI CA (GO–DTPA–Gd). We have demonstrated that the GO–DTPA–Gd system significantly improves MRI T1 relaxivity and leads to a better cellular MRI contrast effect than Magnevist, a commercially used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface of GO sheets via physisorption. Thus-prepared GO–DTPA–Gd/DOX shows significant cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to build a GO-based theranostic nanoplatform with T1-weighted MRI, fluorescence imaging, and drug delivery functionalities.Keywords: cellular imaging; contrast agents; graphene oxide; MR imaging; theranostics;

In order to improve the solubility of diflunisal (DIF), and hence the oral bioavailability, two 2:1 diflunisal cocrystals were prepared by solution crystallization from ethanol with nicotinamide (NIC) or isonicotinamide (ISO) as coformer. The cocrystals were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), as well as liquid- and solid-state nuclear magnetic resonance (LNMR and SSNMR). PXRD and NMR measurements indicate that the pure 2:1 cocrystals can be obtained even the DIF and coformer started from different ratios (2:1, 1:1 and 1:2). FTIR and 13C SSNMR measurements provide clues about the formation of amide–carboxylic acid heterosynthon and pyridine–carboxylic acid heterosynthon between DIF and coformer. The melting points of DIF-NIC and DIF-ISO cocrystals are 195 and 182 °C respectively, indicating their favorable thermal stability. Meanwhile, the two cocrystals exhibit faster dissolution rates and higher aqueous solubilities than the pure drug compound.

To improve the dissolution and hence the oral bioavailability, amorphous felodipine (FEL) solid dispersions (SDs) with Kollidon® VA 64 (PVP/VA) were prepared. Hot-melt extrusion was employed with an extruding temperature below the melting point (Tm) of FEL. X-ray powder diffraction (XRPD) and 13C CP/MAS nuclear magnetic resonance (NMR) measurements show that the extrudates are amorphous. The intermolecular interaction between FEL and PVP/VA in SDs was investigated by Fourier transform infrared spectroscopy, 15N CP/MAS NMR, and 1H high-resolution MAS NMR. Furthermore, a single glass transition temperature (Tg) was detected by differential scanning calorimetry in addition to a single 1H T1 or T1rho relaxation time detected by 13C NMR signals. These results confirm that the extru-dates contain FEL dispersed into the polymer matrix at a molecular level with no detectable phase separation. This molecular-scale mixing results in a significantly faster dissolution rate compared with the pure crystalline FEL. Additionally, the molecular-scale mixing prevents the amorphous drug from recrystallizing even after being stored at 40°C/75% Relative Humidity for 2 months.

•We first develop periodic mesoporous organosilicas based on the framework of amino acid.•A novel amino acid bridged organosilane based on aspartic acid is prepared.•Ordered 2D mesoporous structure is formed in the aspartic acid bridged PMOs materials.Novel periodic mesoporous organosilicas materials (PMOs) based on the flexible skeleton of aspartic acid were synthesized by the co-condensation of aspartic acid-bridged organosilane (Asp-BOSP) and tetraethyl orthosilicate (TEOS) in an acidic medium, using the Pluronic P123 surfactant as a template. Furthermore, a new amino acid organosilane was developed by the simple reaction between traditional organosilicone ((3-aminopropyl) trimethoxysilane) and aspartic acid. The small-angle XRD and N2 adsorption-desorption isotherms demonstrate that these PMOs materials possess ordered 2D hexagonal mesostructures in the region of low molar concentrations of Asp-BOSP (⩽10%). Analysis of FTIR and 29Si MAS solid-state NMR confirm that the aspartic acid is incorporated into the framework of the PMOs materials.