Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.

A supramolecular adduct of tegafur and syringic acid: the first tegafur-nutraceutical cocrystal with perfected in vitro and in vivo characteristics as well as synergized anticancer activities

The in vitro and in vivo properties as well as synergistic antitumor activities of the first tegafur-nutraceutical cocrystal are reported.

Cyclodextrin-Driven Formation of Double Six-Ring (D6R) Silicate Cage: NMR Spectroscopic Characterization from Solution to Crystals

Identification and isolation of secondary building units (SBUs) from synthesis media of zeolites still represent a challenging task for chemists. The cage structure anion Si12O3012− known as the double six-ring (D6R) was synthesized from α-cyclodextrin (α-CD) mediated alkaline silicate solutions and conditions of its stability and reactivity in aqueous solution were studied by using nuclear magnetic resonance (NMR) spectroscopy. A single crystal X-ray diffraction (XRD) analysis revealed a novel polymorph of the hybrid complex K12Si12O30·2α-CD·nD2O (n ≈ 30–40), which crystallizes in the orthorhombic C2221 space group symmetry with a = 14.841(4) Å, b = 25.855(6) Å, and c = 41.91(1) Å. The supramolecular adduct of the silicate anion sandwiched by two α-CDs forms a perfect symmetry matching the H-bonding donor-acceptor system between the organic macrocycle and the D6R unit. The driving force of such a hybrid assembly has found to be strongly dependent on the nature of the cation present as large alkali counter ions (K+, Rb+ and Cs+), which stabilize the D6R structure acting as templates. Lastly, we provided the first 29Si MAS NMR measurement of 3Q Si in an isolated D6R unit that allows the verification of the linear correlation between the chemical shift and <SiOSi> bond angle for 3Q Si species in DnR cages (n = 3, 4, 6).