Polymorphism and polymerisation of acrylic and methacrylic acid at high pressure

The polymorphism and polymerisation of two related acids have been investigated under high pressure conditions. Acrylic acid crystallises as a new polymorph at 0.65 GPa whilst methacrylic acid crystallises in a new polymorph at a higher pressure of 1.5 GPa. Both these new polymorphs exhibit similar hydrogen bonding motifs to the low temperature phases, however, the molecular packing differs significantly

Accessing mefenamic acid form II through high-pressure recrystallization

High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, Mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using Diamond Anvil Cell. Comparison of the crystal structures shows that the efficient packing of molecules in Form II has been enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallisation at high pressure results

Antisolvent addition at extreme conditions

This article describes the use of antisolvent addition at high-pressure to aid precipitation and recovery of high-pressure phases to ambient pressure. Paracetamol (PCM) was used as a model system to demonstrate the principle due to the extensive literature of paracetamol at high-pressure and ambient pressure. We have observed that we are able to recover the orthorhombic form of paracetamol to ambient pressure using this technique, although solvent-mediated transformations are a hurdle. During this investigation we observed a new methanol solvate of paracetamol that is simlar in structure to the known form. The methanol solvate is stable to 0.2 GPa before transformation to the orthorhombic form that is known to be the stable form at high pressure

Supramolecular hair dyes : a new application of cocrystallization

The manuscript presents the first report of hair dyes of various colors formed by the cocrystallization reactions. Unlike the most popular oxidative hair dye (OHD) products, these dyes are NH3 free and do not require H2O2 as a color developer. The importance of these new hair dyes products is further enhanced by recent reports which indicate that some of the OHDs may be carcinogeni

Sweet like chocolate

In the July issue of Acta Crystallographica Section C, Nicholls et al. (2019[Nicholls, D., Elleman, C., Shankland, N. & Shankland, K. (2019). Acta Cryst. C75, 904-909.]) report the discovery of a new polymorph of αβ-D-lactose through the oven drying of concentrated aqueous solutions of D-lactose. The authors inter­est in this system was piqued in relation to the properties of chocolate crumb and the process by which the crumb is made. The drying process by which the crumb is produced is a potential mine of inter­esting solid-state transformations and in this case the authors simplified the system from a complex mixture of milk and sucrose to a concentrated aqueous solution of lactose. This simplification of the system has enabled the authors to focus in on the phase transitions that occur in the system and analyse the crystallization products with high-quality crystallographic information. Lucky for Acta Crystallographica Section C that such a delicious structural study was published here

Polymorphism of Polymeric Drug Excipients at High Pressure

The aims of the current study were to investigate the effect of pressure on polyethyelene glycol (PEG4000) to create an effective drug delivery system for poorly water soluble drugs, with a view to increasing their bioavailability. The effect of pressure exerted by a diamond anvil cell on PEG4000 and the model drug respectively, and the polymer and drug together were examined using Raman and infrared spectroscopy. PEG4000 was shown to melt at 5GPa using a diamond anvil cell, as exemplified by flowing. Hydrocortisone does not melt under pressure or physically change and thus could be effectively encapsulated in the PEG at high pressure. Differential scanning calorimetry was carried out on the samples. PEG4000 was observed to melt over an average range of 58.67 to 63ºC and hydrocortisone was observed to melt over an average range of 223.49 to 228.15ºC. The latter was observed to change from a white powder into a marigold yellow liquid. Thermogravimetric analysis revealed degradation occurred at temperatures distinct from the melting range, thus when PEG melts at high pressure it is not degrading. Drug release testing was carried out on the diamond anvil cell samples in simulated intestinal and gastric fluids over 8 hours in a pulsatile fashion, mimicking traditional cortisol replacement therapy but with one administration rather than multiple administrations daily. Scale up using a large volume press was investigated. Drug release occurred over 10 days in a similar pulsatile fashion to the small volume study. Unfortunately due to the highly unstable nature of hydrocortisone in aqueous solutions future work may require the use of stabilisers such as fructose or disodium edentate. Overall PEG does increase the solubility of poorly soluble drugs but further work could be carried out in terms of formulation

Crystal structure of a mixed solvated form of amoxapine acetate

The mixed solvated salt 4-(2-chloro­dibenzo[b,f][1,4]oxazepin-11-yl)piperazin-1-ium acetate-acetic acid-cyclo­hexane (2/2/1), C17H17ClN3O+·C2H3O2-·C2H4O2·0.5C6H12, crystallizes with one mol­ecule of protonated amoxapine (AXPN), an acetate anion and a mol­ecule of acetic acid together with half a mol­ecule of cyclo­hexane. In the centrosymmetric crystal, both enanti­omers of the protonated AXPN mol­ecule stack alternatively along [001]. Acetate anions connect the AXPN cations through N-H...O hydrogen bonding in the [010] direction, creating a sheet lying parallel to (100). The acetic acid mol­ecules are linked to the acetate anions via O-H...O hydrogen bonds within the sheets. Within the sheets there are also a number of C-H...O hydrogen bonds present. The cyclo­hexane solvent mol­ecules occupy the space between the sheets

Hidden solvates and transient forms of trimesic acid

This article discusses the formation of trimesic acid (TMA) solvates with ethanol, isopropyl alcohol and dimethylformamide via liquid-assisted grinding and slurry experiments. Through the use of X-ray diffraction methods, we highlight the formation of a new ethanol solvate of TMA that completes the series of alcohol solvates observed, a temperature-induced phase transition in the isopropyl alcohol solvate between 233 K and 243 K, and a transient 1:3 solvate with dimethylformamide that mimics a previously identified dimethylsulfoxide solvate. The alcohol structures possess a TMA framework that is geometrically similar where the intermolecular energies between TMA molecules are equivalent. We have observed that increasing the length of the alcohol induces an increase in the distortion of the TMA framework to accommodate the longer alkyl tails

Polymorphism in p-Aminobenzoic Acid

We review the polymorphism of p-aminobenzoic acid (pABA), a model drugcompound whose crystallisation and polymorphic behaviour has been extensively studied in recent years. Beyond the well-known and characterised α and β forms, pABA also crystallises as a γ polymorph, which is structurally similar to the α form. In addition we also compare the newly reported δ form, obtained by high pressure crystallisation and through compression of the α-form. A structural analysis and comparison of all of the forms is presented, the conditions by which each of them is obtained summarised. Crystal structure prediction calculations have also been carried out in order to probe the solid form energy landscape of this compound. The overall picture of the polymorphism of pABA, reveals, surprisingly, the rarity of the β form