Metal-Organic Framework (MOF) Morphology Control by Design.

Exerting morphological control over metal-organic frameworks (MOFs) is critical for determining their catalytic performance and to optimize their packing behavior in areas from separations to fuel gas storage. A mechanism-based approach to tailor the morphology of MOFs is introduced and experimentally demonstrated for five cubic Zn O-based MOFs. This methodology provides three key features: 1) computational screening for selection of appropriate additives to change crystal morphology based on knowledge of the crystal structure alone; 2) use of additive to metal cluster geometric relationships to achieve morphologies expressing desired crystallographic facets; 3) potential for suppression of interpenetration for certain phases.

Optimizing Hydrogen Storage in MOFs through Engineering of Crystal Morphology and Control of Crystal Size.

Metal-organic frameworks (MOFs) are promising materials for hydrogen storage that fail to achieve expected theoretical values of volumetric storage density due to poor powder packing. A strategy that improves packing efficiency and volumetric hydrogen gas storage density dramatically through engineered morphologies and controlled-crystal size distributions is presented that holds promise for maximizing storage capacity for a given MOF. The packing density improvement, demonstrated for the benchmark sorbent MOF-5, leads to a significant enhancement of volumetric hydrogen storage performance relative to commercial MOF-5.

Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal-Organic Framework (MOF).

Encapsulating a drug molecule into a water-reactive metal-organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated.

Far-Infrared Spectroscopy as a Probe for Polymorph Discrimination.

Pharmaceutical crystalline polymorph and amorphous form detection and quantification is a standard requirement in the pharmaceutical industry. Infrared (IR) spectroscopy provides an important probe for the characterization of polymorphs. Nonetheless, characterization and discrimination among polymorphs using mid-IR spectroscopy is not always possible in part because the technique mainly probes vibrational modes arising from functional groups in the sample.

Curcumin-Artemisinin Coamorphous Solid: Xenograft Model Preclinical Study.

Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR), we evaluated Curcumin-Pyrogallol (CUR-PYR) cocrystal and Curcumin-Artemisinin (CUR-ART) coamorphous solid.

Structure and physicochemical characterization of a naproxen-picolinamide cocrystal.

Naproxen (NPX) is a nonsteroidal anti-inflammatory drug with pain- and fever-relieving properties, currently marketed in the sodium salt form to overcome solubility problems; however, alternative solutions for improving its solubility across all pH values are desirable. NPX is suitable for cocrystal formation, with hydrogen-bonding possibilities via the COOH group. The crystal structure is presented of a 1:1 cocrystal of NPX with picolinamide as a coformer [systematic name: (S)-2-(6-methoxynaphthalen-2-yl)propanoic acid-pyridine-2-carboxamide (1/1), CHO·CHNO].

Crystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins.

The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate.

Cocrystals and alloys of nitazoxanide: enhanced pharmacokinetics.

Two isomorphous cocrystals of nitazoxanide (NTZ) with p-aminosalicylic acid (PASA) and p-aminobenzoic acid (PABA) as well as their alloys were prepared by slurry and grinding techniques. The cocrystals exhibit faster dissolution rates and higher pharmacokinetic properties compared to the reference drug, and surprisingly the cocrystal alloy NTZ-PABA : NTZ-PASA (0.75 : 0.

Color polymorphs of aldose reductase inhibitor epalrestat: configurational, conformational and synthon differences.

We report five crystalline polymorphs and an amorphous phase of epalrestat together with configurational isomerism and color behavior: form I (deep red), form II (deep orange), form III (bright yellow), form IV (yellow), and form V (orange) are in the E,Z configuration of the drug, and a Z,Z isomer (bright yellow). Two pathways are identified for polymorph conversion: direct transformation of the E,Z isomer and another pathway via the Z,Z isomer to the E,Z polymorphs. From a pharmaceutical perspective, the stability of polymorphs was established under grinding, solvent slurry and thermal conditions: form I (thermodynamic) > form II > form V > form III > form IV (least stable).

Andrographolide: solving chemical instability and poor solubility by means of cocrystals.

The bioactive agent andrographolide was screened with pharmaceutically acceptable coformers to discover a novel solid form that will solve the chemical instability and poor solubility problems of this herbal medicine. Liquid-assisted grinding of andrographolide with GRAS (generally regarded as safe) coformers in a fixed stoichiometry resulted in cocrystals with vanillin (1:1), vanillic acid (1:1), salicylic acid (1:1), resorcinol (1:1), and guaiacol (1:1). All the crystalline products were characterized by thermal, spectroscopic, and diffraction methods.

Fast dissolving eutectic compositions of curcumin.

The bioactive herbal ingredient curcumin was screened with pharmaceutically acceptable coformers to discover solid-state forms of high solubility. Mechano-chemical grinding of curcumin with cocrystal formers in a fixed stoichiometry ratio resulted in binary eutectic compositions of curcumin-coformer with nicotinamide (1:2), ferulic acid (1:1), hydroquinone (1:1), p-hydroxybenzoic acid (1:1), and l-tartaric acid (1:1). The eutectic nature of the product crystalline solids was established by differential scanning calorimetry, and the absence of hydrogen-bonded crystalline phases such as cocrystals/salts was ascertained by powder X-ray diffraction, IR-Raman, and solid-state NMR spectroscopy.

Novel furosemide cocrystals and selection of high solubility drug forms.

Furosemide was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover cocrystals of improved physicochemical properties, that is high solubility and good stability. Eight novel equimolar cocrystals of furosemide were obtained by liquid-assisted grinding with (i) caffeine, (ii) urea, (iii) p-aminobenzoic acid, (iv) acetamide, (v) nicotinamide, (vi) isonicotinamide, (vii) adenine, and (viii) cytosine. The product crystalline phases were characterized by powder x-ray diffraction, differential scanning calorimetry, infrared, Raman, near IR, and (13) C solid-state NMR spectroscopy.