Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.

To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.

Combination of submicroemulsion and phospholipid complex for novel delivery of ursodeoxycholic acid.

The objective of this study was to prepare and characterize ursodeoxycholic acid submicron emulsion (UA-SME) loaded with ursodeoxycholic acid phytosomes (UA-PS) and optimize the process variables. A screening experiment with response surface methodology with Box-Behnken design (BBD) was used to optimize the process parameters of UA-SME. The blood concentrations of UA after oral administration of UA-SME and UA coarse drug were assayed. The optimum process conditions were finally obtained by using a desirability function. It was found that stirring velocity, homogenization pressure and homogenization cycles were the most important variables that affected the particles size, polydispersity index and entrapment efficiency of UA-SME. Results showed that the optimum stirring velocity, homogenization pressure and cycles were 16 000 rpm, 60 MPa and 10 cycles, respectively. The mean diameter, polydispersity index and entrapment efficiency of UA-SME were 251.9 nm, 0.241 and 74.36%, respectively. Pharmacokinetic parameters of UA and UA-SME in rats were Tmax 2.215 and 1.489 h, Cmax 0.0364 and 0.1562 µg/mL, AUC0-∞ 3.682 and 13.756 µg h/mL, respectively. The bioavailability of UA in rats was significantly different (p < 0.05) after oral administration of UA-SME compared to those of UA coarse drug. This was due to improvement of the hydrophilicity and lipophilic property of UA-SME.

Syntheses, structures, luminescence, and magnetic properties of one-dimensional lanthanide coordination polymers with a rigid 2,2'-bipyridine-3,3',6,6'-tetracarboxylic acid ligand.

A series of novel one-dimensional (1-D) lanthanide coordination polymers (CPs), with the general formula {[Ln(bptcH)(H(2)O)(2)]·H(2)O}(n) (Ln = Nd(III) (1), Eu(III) (2), Gd(III) (3), Tb(III) (4), Dy(III) (5), Ho(III) (6), or Er(III) (7)) have been synthesized by the solvothermal reactions of the corresponding lanthanide(III) picrates and 2,2'-bipyridine-3,3',6,6'-tetracarboxylic acid (bptcH(4)). These polymers have been structurally characterized by single-crystal X-ray diffraction, IR, PXRD, thermogravimetric (TGA), and elemental analysis. Coordination polymers 1-7 are isostructural; they possess the same 3D supramolecular architectures and crystallize in triclinic space group P1̅. The frameworks constructed from dinuclear lanthanide building blocks exhibit one-dimensional double-stranded looplike chain architectures, in which the bptcH(3-) ions adopted hexadentate coordination modes. The Eu(III) (2) and Tb(III) (4) polymers exhibit characteristic photoluminescence in the visible region. The magnetic properties of polymers 2, 3, and 5 have been investigated through the measurement of their magnetic susceptibilities over the temperature range of 1.8-300 K.

2,4-Diiodo-3-nitro-anisole.

IN THE TITLE COMPOUND (SYSTEMATIC NAME: 1,3-diiodo-4-meth-oxy-2-nitro-benzene), C(7)H(5)I(2)NO(3), the dihedral angle between the benzene ring and the nitro group is 88.0 (3)°, and the methyl group lies almost in the same plane as the ring [deviation = 0.034 (6) Å]. In the crystal, aromatic π-π stacking occurs between inversion-related rings [centroid-centroid separation = 3.865 (3) Šand slippage = 0.642 Å]. A possible weak C-I⋯π inter-action occurs [I⋯π = 3.701 (2) Šand C-I⋯π = 130.18 (13)°], but there are no significant inter-molecular I⋯I contacts.

3,15-Dimeth-oxy-10-methyl-tricyclo-[9.4.0.0]penta-deca-1(11),2(7),3,5,9,12,14-heptaen-8-one.

The title mol-ecule, C(18)H(16)O(3), contains three fused rings, of which the seven-membered cyclo-hept-2-enone ring has a screw-boat conformation. The two meth-oxy-phenyl rings make a dihedral angle of 50.4 (2)°. In the crystal, mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds, leading to a three-dimensional supra-molecular architecture.