Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations.

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations to overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the methods more sustainable and cost-efficient. A Secoya microfluidic crystallization technology-based continuous liquid antisolvent crystallization (SCT-CLASC) process was optimized and afterward compared to an earlier developed microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup, using itraconazole (ITZ) as the model drug. After operating parameter optimization and downstream processing (i.

Bottom-up production of injectable itraconazole suspensions using membrane technology.

Bottom-up production of active pharmaceutical ingredient (API) crystal suspensions offers advantages in surface property control and operational ease over top-down methods. However, downstream separation and concentration pose challenges. This proof-of-concept study explores membrane diafiltration as a comprehensive solution for downstream processing of API crystal suspensions produced via anti-solvent crystallization.

Development of long-acting injectable suspensions by continuous antisolvent crystallization: An integrated bottom-up process.

Our present work elucidated the operational feasibility of direct generation and stabilization of long-acting injectable (LAI) suspensions of a practically insoluble drug, itraconazole (ITZ), by combining continuous liquid antisolvent crystallization with downstream processing (i.e., centrifugal filtration and reconstitution).

(E,E)-N-(2,3,4,5,6-Penta-fluoro-benzyl-idene)-N-(3,4,5-trimeth-oxy-benzyl-idene)benzene-1,4-diamine.

The title compound, C(23)H(17)F(5)N(2)O(3), forms a layered centrosymmetric crystal structure in which C-H⋯F inter-actions are responsible for the formation of planar ribbons along [110], meth-oxy-meth-oxy (C-H⋯O) inter-actions for the formation of layers parallel to [[Formula: see text]13], and OCH(3)⋯π and C-F⋯π inter-actions for the stacking of these layers.

(E)-4-[2-(3,4,5-trimethoxyphenyl)ethenyl]nitrobenzene and its 'bridge-flipped' analogues.

The solid-state structures of three push-pull acceptor-π-donor (A-π-D) systems differing only in the nature of the π-spacer have been determined. (E)-1-Nitro-4-[2-(3,4,5-trimethoxyphenyl)ethenyl]benzene, C(17)H(17)NO(5), (I), and its 'bridge-flipped' imine analogues, (E)-3,4,5-trimethoxy-N-(4-nitrobenzylidene)aniline, C(16)H(16)N(2)O(5), (II), and (E)-4-nitro-N-(3,4,5-trimethoxybenzylidene)aniline, C(16)H(16)N(2)O(5), (III), display different kinds of supramolecular networks, viz. corrugated planes, a herringbone pattern and a layered structure, respectively, all with zero overall dipole moments.

4,4'-Bis[2-(3,5-dimeth-oxy-phen-yl)ethen-yl]biphen-yl.

The title compound, C(32)H(30)O(4), crystallizes with three different conformers of the same mol-ecule in the asymmetric unit, which explains the unusually large unit cell volume. The supra-molecular structure is based on inter-actions involving the meth-oxy groups [C⋯O contacts between 3.090 (2) and 3.

Conformational polymorphism of (E,E)-N,N'-bis(4-nitrobenzylidene)benzene-1,4-diamine.

Two polymorphs of (E,E)-N,N'-bis(4-nitrobenzylidene)benzene-1,4-diamine, C(20)H(14)N(4)O(4), (I), have been identified. In each case, the molecule lies across a crystallographic inversion centre. The supramolecular structure of the first polymorph, (I-1), features stacking based on π-π interactions assisted by weak hydrogen bonds involving the nitro groups.

Dynamic disorder in the crystal structure of an organic semiconductor: an unusual phase transition involving the heat capacity.

(E,E)-1-[2-(4-Nitrophenyl)ethenyl]-4-[2-(2,4-dimethoxyphenyl)ethenyl]benzene was characterised by X-ray diffraction and shown to be dynamically disordered at room temperature. The structure was re-determined over a range of temperatures to infer the thermodynamic parameters related to this disorder. A phase transition of third order according to the Ehrenfest classification scheme was discovered.

Synthesis and structures of substituted triphenyl(phenylimino)phosphoranes.

Three substituted triphenyl(phenylimino)phosphoranes, namely (4-cyanophenylimino)triphenylphosphorane, C(25)H(19)N(2)P, (I), (4-nitrophenylimino)triphenylphosphorane, C(24)H(19)N(2)O(2)P, (II), and (3-nitrophenylimino)triphenylphosphorane, C(24)H(19)N(2)O(2)P, (III), were synthesized as precursors for the preparation of substituted diphenylcarbodiimides. All three compounds display a supramolecular arrangement in which the substituted benzene rings are organized in an antiparallel fashion. The nitro group on the ring participates in C-H.

2-(4-Formyl-2,6-dimeth-oxy-phenoxy)-acetic acid.

In the title compound, C(11)H(12)O(6), the aldehyde group is disordered over two sites in a 0.79:0.21 ratio.

4-[(E)-2-(2,4,6-Trinitro-phenyl)ethyl-idene]benzonitrile.

In the crystal of the title compound, C(15)H(8)N(4)O(6), the mol-ecules are organized in layers due to their linkage by weak C-H⋯N hydrogen bonds. The layers are themselves inter-connected by weak C-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distances = 3.8690 (15) and 3.

3-(2-Formyl-phen-oxy)propanoic acid.

In the structure of the title compound, C(10)H(10)O(4), the carboxyl group forms a catemer motif in the [100] direction instead of the expected dimeric structures. The carboxylic acid group is found in the syn conformation and the three-dimensional organization in the crystal is based on C-H⋯O and O-H⋯O interactions.

(E)-1-(2,4,6-Trimeth-oxy-phen-yl)pent-1-en-3-one.

The title compound, C(14)H(18)O(4), was obtained unintentionally as the major product of an attempted synthesis of (E,E)-2,5-bis-[2-(2,4,6-trimeth-oxy-phen-yl)ethen-yl]pyrazine. The crystal packing features layers based on two weak C-H⋯O hydrogen bonds involving the O atom of the carbonyl group and two O(meth-oxy)⋯C(meth-oxy) inter-actions [3.109 (2) Å].