Study of Different Crystal Habits of Aprepitant: Dissolution and Material Attributes

In the present study, aprepitant (APT) was selected to find its suitable crystal habit, which can improve its existing poor dissolution and manufacturing processability. Solvents were screened out for solubility analysis of APT and further crystal habit modification. Solid-state characterization studies like powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier infrared spectroscopy (FTIR) distinguished that tabular crystal habit was generated from acetone (APT-AC) and long tabular crystal habit was generated from ethyl acetate (APT-EA). Kawakita analysis and powder flow property studies showed that APT-EA is cohesive, has poor flow property and low bulk density compared to APT-AC (p < 0.05). Heckel plots reflected that APT-EA shows higher fragmentation and particle rearrangement during the initial stages as indicated by the higher intercept values. Higher slopes in APT-EA and APT-AC confirmed better plasticity but lower yield pressure in APT-AC proved good plastic deformation compared to APT-EA (p < 0.05). The dissolution profile of the APT-EA was found to be better than that of APT-AC. Overall, it can be concluded that APT-AC crystal habit has a better flow rate, tensile strength, and plasticity whereas APT-EA has better dissolution.

Mindfulness: Principles and Application to Decrease Opiate Use in Primary Care With an Osteopathic Component

Mindfulness is a focused approach toward accepting one’s thoughts without judgment or perseveration, with ancient Indo-Sino-Tibetan philosophical origins. Many variations exist; however, they typically include focused attention where one concentrates on a specific sensation such as breathing and open monitoring where one concentrates on consciousness itself. Mindfulness-based interventions (MBIs) are specific, organized, targeted methods to teach mindfulness with specific goals. MBIs have shown benefit in pain patients. MBIs teach the individual the concept of pain coping, encouraging cognitive flexibility and attempting to discourage the fear or alarm reaction of pain, instead focusing on the quality of life and functionality. Mindfulness-based stress reduction (MBSR) showed a 30% significant improvement in pain intensity and pain coping at six months in patients with chronic low back pain, compared to opiates and NSAIDs, which showed no benefit. MBIs have also shown benefit in addiction, as they help the individual relearn to control cravings, habit modification and attempt to restore the natural reward system while improving regulation of emotions. Applications to opiate use disorder are significant as patients learn to enjoy the lifestyle of recovery and learn to believe they can improve. Additionally, other comorbid conditions are known to improve with MBIs and mindfulness-based principles support the holistic principle of mind, spirit and body consistent with osteopathic medicine.

Synthesis and Visualization of a Novel Fluorescent-Tagged Polymeric Antiscalant during Gypsum Crystallization in Combination with Bisphosphonate Fluorophore

An attempt to reveal the mechanisms of scale inhibition with the use of two different fluorescent-tagged antiscalants at once is undertaken. To reach the goal, a novel 1,8-naphthalimide-tagged polyacrylate (PAA-F2) is synthesized and tested separately and jointly with 1,8-naphthalimide-tagged bisphosphonate (HEDP-F) as a gypsum scale inhibitor within the frames of NACE Standard TM0374-2007. Here, it is found that at a dosage of 10 mg·dm−3 it provides a much higher inhibition efficiency (96%) than HEDP-F (32%). A PAA-F2 and HEDP-F blend (1:1 mass) has an intermediate efficacy (66%) and exhibits no synergism relative to its individual components. The visualization of PAA-F2 revealed a paradoxical effect: an antiscalant causes modification of the CaSO4·2H2O crystals habit, but does not interact with them, forming particles of its own solid complex [Ca-PAA-F2]. This paradox is interpreted in terms of the “nano/microdust” concept, prioritizing the bulk heterogeneous nucleation step, while an ability of the scale inhibitor to block the nucleus growth at the next steps is proven to be of secondary importance. At the same time, HEDP-F does not change the gypsum crystals morphology, although this antiscalant is completely located on the surface of the scale phase. The PAA-F2 and HEDP-F blend revealed an accumulation of both antiscalants in their own [Ca-PAA-F2/Ca-HEDP-F] phase with some traces of HEDP-F and PAA-F2 on the CaSO4·2H2O crystals surface. Thus, the visualization of two different antiscalants separately and jointly applied to gypsum deposition demonstrates differences in phosphonic and polymeric inhibitors location, and a lack of causal relationship between antiscalant efficiency and scale particle habit modification. Finally, it is shown that the confocal microscopy of several fluorescent antiscalant blends is capable of providing unique information on their interrelationships during scale deposition.

Impact of Crystal Habit on Solubility of Ticagrelor

Drugs with poor biopharmaceutical performance are the main obstacle to the development and design of medicinal preparations. The anisotropic surface chemistry of different surfaces on the crystal influences its physical and chemical properties, such as solubility, tableting, etc. In this study, the antisolvent crystallization and rapid-cooling crystallization were carried out to tune the crystal habits of ticagrelor (TICA) form II. Different crystal habits of ticagrelor (TICA) form II (TICA-A, TICA-B, TICA-C, TICA-D, and TICA-E) were prepared and evaluated for solubility. The single-crystal diffraction (SXRD) indicated that TICA form II belongs to the triclinic P1 space group with four TICA molecules in the asymmetric unit. The TICA molecules are generated through intermolecular hydrogen bonds along the (010) direction, forming an infinite molecular chain, which are further stacked by hydrogen bonds between hydroxyethoxy side chains, forming molecular circles composed of six TICA molecules along bc directions. Thus, in the case of TICA form II, hydrogen bonds drive growth along one axis (b-axis), which results in the formation of mostly needle-shape crystals. Morphology and face indexation reveals that (001), (010) and (01-1) are the main crystal planes. Powder diffractions showed that five habits have the same crystal structure and different relative intensity of diffraction peak. The solubility of the obtained crystals showed the crystal habits affect their solubility. This work is helpful for studying the mechanism of crystal habit modification and its effect on solubility.

Tuning the Crystal Habits of Organic Explosives by Antisolvent Crystallization: The Case Study of 2,6-dimaino-3,5-dinitropyrazine-1-oxid (LLM-105)

Crystallization is one of the most important methods in the crystal habit control of explosive products. For this study, the antisolvent crystallization experiments were carried out to tune the crystal habits of 2,6-dimaino-3,5-dinitropyrazine-1-oxid (LLM-105). Dimethyl sulphoxide (DMSO) was used as an organic solvent. Water, methanol, acetic acid, nitromethane, acetone, ethanol, methylene chloride, o-dichlorobenzene, and toluene were selected as antisolvents. The X-shaped, spherical cluster-like, rod-like, needle-like, and dendritic crystals were successfully produced by varying the kind of the antisolvent. These results manifested that the polarity and functional groups of antisolvent molecules played important roles in the crystal habits of LLM-105 explosive. The powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) measurements indicated that these antisolvents just tuned the crystal habit of LLM-105 but did not change the crystal structure. The differential scanning calorimetry (DSC) and thermogravimetry (TG) results of the obtained crystals showed that the crystal habits significantly affected the thermal properties. This study can contribute to the investigation of the mechanism of antisolvent-induced crystal habit modification and screen out the efficient antisolvents.