Current needs of the pharmaceutical industry: opportunities and challenges for implementing novel drying technologies

[EN] Commercial drying methods are limited either by high production costs or significant quality loss due to process-related stresses. The near-ubiquitous use of freeze-drying in the pharmaceutical industry makes it the standard to which other drying technologies are compared. However, the shortcomings of lyophilization warrant evaluation of new techniques and the benefits they offer, such as compatibility with continuous manufacturing. Novel drying technologies must also overcome barriers to commercial implementation including, but not limited to, scalability and integration into a GMP environment. There remain several opportunities for further research which direct focus and investment strategy for the next generation pharmaceutical drying technologies.Langford, A.; Luy, B.; Ohtake, S. (2018). Current needs of the pharmaceutical industry: opportunities and challenges for implementing novel drying technologies. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1997-2002. https://doi.org/10.4995/IDS2018.2018.8354OCS1997200

Complexity of decoupling and time-reversal for n spins with pair-interactions: Arrow of time in quantum control

Well-known Nuclear Magnetic Resonance experiments show that the time evolution according to (truncated) dipole-dipole interactions between n spins can be inverted by simple pulse sequences. Independent of n, the reversed evolution is only two times slower than the original one. Here we consider more general spin-spin couplings with long range. We prove that some are considerably more complex to invert since the number of required time steps and the slow-down of the reversed evolutions are necessarily of the order n. Furthermore, the spins have to be addressed separately. We show for which values of the coupling parameters the phase transition between simple and complex time-reversal schemes occurs.Comment: Completely rewritten, new lower bounds on the number of time steps, applications and references adde

Academic Procrastination, Self-Esteem and Self-Efficacy in University Students: Comparative Study in Two Peruvian Cities

The present study aims to determine the relationship between academic procrastination, self-esteem and self-efficacy in undergraduate students in two Peruvian cities. The population consisted of 13,767 students, from which a sample of 1,494 was extracted. The subjects were selected from eight universities: five private and one public, from the city of Metropolitan Lima; and two universities, one public and one private, from the city of Arequipa. The instruments used were the Academic Procrastination Scale (EPA), the Scale of Specific Perceived Self-Efficacy in Academic Situations (EAPESA) and the Rosemberg Self-Esteem Scale. The results allow us to conclude that, in terms of perceived effectiveness, the relationship is slightly higher in the city of Arequipa, reiterating this with respect to academic procrastination, where the relationship is also slightly higher. Finally, with regard to self-esteem, the trend continues to indicate a greater relationship in Arequip

Rhodium(I) and Iridium(I) complexes of the conformationally rigid IBioxMe4Ligand : computational and experimental studies of unusually tilted NHC coordination geometries

Computational methods have been used to analyze distorted coordination geometries in a coherent range of known and new rhodium(I) and iridium(I) complexes containing bioxazoline-based NHC ligands (IBiox). Such distortions are readily placed in context of the literature through measurement of the Cnt(NHC)–CNCN–M angle (ΘNHC; Cnt = ring centroid). On the basis of restricted potential energy calculations using cis-[M(IBioxMe4)(CO)2Cl] (M1; M = Rh, Ir), in-plane (yawing) tilting of the NHC was found to incur significantly steeper energetic penalties than orthogonal out-of-plane (pitching) movement, which is characterized by noticeably flat potential energy surfaces. Energy decomposition analysis (EDA) of the ground-state and pitched structures of M1 indicated only minor differences in bonding characteristics. In contrast, yawing of the NHC ligand is associated with a significant increase in Pauli repulsion (i.e., sterics) and reduction in M→NHC π back donation, but is counteracted by supplemental stabilizing bonding interactions only possible due to the closer proximity of the methyl substituents with the metal and ancillary ligands. Aided by this analysis, comparison with a range of carefully selected model systems and EDA, distorted coordination modes in trans-[M(IBioxMe4)2(COE)Cl] (M2; M = Rh, Ir) and [M(IBioxMe4)3]+ (M3; M = Rh, Ir) have been rationalized. Steric interactions were identified as the major contributing factor and are associated with a high degree of NHC pitching. In the case of Rh3, weak agostic interactions also contribute to the distortions, particularly with respect to NHC yawing, and are notable for increasing the bond dissociation energy of the distorted ligands. Supplementing the computational analysis, an analogue of the formally 14 VE Rh(I) species Rh3 bearing the cyclohexyl-functionalized IBiox6 ligand ([Rh(IBiox6)3]+, Rh3-Cy) was prepared and found to exhibit an exceptionally distorted NHC ligand (ΘNHC = 155.7(2)°) in the solid state

Optically induced dynamic nuclear spin polarisation in diamond

The sensitivity of magnetic resonance imaging (MRI) depends strongly on nuclear spin polarisation and, motivated by this observation, dynamical nuclear spin polarisation has recently been applied to enhance MRI protocols (Kurhanewicz et al 2011 Neoplasia 13 81). Nuclear spins associated with the 13C carbon isotope (nuclear spin I = 1/2) in diamond possess uniquely long spin lattice relaxation times (Reynhardt and High 2011 Prog. Nucl. Magn. Reson. Spectrosc. 38 37). If they are present in diamond nanocrystals, especially when strongly polarised, they form a promising contrast agent for MRI. Current schemes for achieving nuclear polarisation, however, require cryogenic temperatures. Here we demonstrate an efficient scheme that realises optically induced 13C nuclear spin hyperpolarisation in diamond at room temperature and low ambient magnetic field. Optical pumping of a nitrogen-vacancy centre creates a continuously renewable electron spin polarisation which can be transferred to surrounding 13C nuclear spins. Importantly for future applications we also realise polarisation protocols that are robust against an unknown misalignment between magnetic field and crystal axis

Beyond freeze-drying of biologics: vacuum-foam drying and spray freeze-drying

[EN] The complexity of biotherapeutics in development continues to increase as our capability in discovery and recombinant technology improves. While safety and efficacy remain the two critical aspects of all therapeutics, ensuring adequate stability is a challenge. Freeze-drying is a commonly-used processing technique to enhance the stability of biotherapeutic products, although the lengthy process time and low energy efficiency have led to the search for, and evaluation of, next-generation drying technologies, including spray freeze-drying and vaccum-foam drying. Both processes result in dosage forms that vary considerably from those produced by lyophilization and possess physical properties that may be deemed superior for their intended applications.Langford, A.; Balthazor, B.; Bhatnagar, B.; Tchessalov, S.; Hageman, M.; Lukas, A.; Plitzko, M.... (2018). Beyond freeze-drying of biologics: vacuum-foam drying and spray freeze-drying. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 41-48. https://doi.org/10.4995/IDS2018.2018.7855OCS414