Controlled precipitation for enhanced dissolution rate of flurbiprofen: development of rapidly disintegrating tablets

Objective: The aim of this work was to investigate the potential of controlled precipitation of flurbiprofen on solid surface, in the presence or absence of hydrophilic polymers, as a tool for enhanced dissolution rate of the drug. The work was extended to develop rapidly disintegrated tablets.

Significance: This strategy provides simple technique for dissolution enhancement of slowly dissolving drugs with high scaling up potential.

Methods: Aerosil was dispersed in ethanolic solution of flurbiprofen in the presence and absence of hydrophilic polymers. Acidified water was added as antisolvent to produce controlled precipitation. The resultant particles were centrifuged and dried at ambient temperature before monitoring the dissolution pattern. The particles were also subjected to FTIR spectroscopic, X-ray diffraction and thermal analyses.

Results: The FTIR spectroscopy excluded any interaction between flurbiprofen and excipients. The thermal analysis reflected possible change in the crystalline structure and or crystal size of the drug after controlled precipitation in the presence of hydrophilic polymers. This was further confirmed by X-ray diffraction. The modulation in the crystalline structure and size was associated with a significant enhancement in the dissolution rate of flurbiprofen. Optimum formulations were successfully formulated as rapidly disintegrating tablet with subsequent fast dissolution.

Conclusions: Precipitation on a large solid surface area is a promising strategy for enhanced dissolution rate with the presence of hydrophilic polymers during precipitation process improving the efficiency.     

Comprehensive numerical modelling of the hot isostatic pressing of Ti-6Al-4V powder: From filling to consolidation

Hot Isostatic Pressing (HIP) is a manufacturing process for production of near-net-shape components, where models based on Finite Element Method (FEM) are generally used for reducing the expensive experimental trials for canister design. Researches up to date implement in the simulation a uniform powder relative density distribution prior HIPping. However, it has been experimentally observed that the powder distribution is inhomogeneous after filling, leading to a non-uniform tool shrinkage. In this study a comprehensive numerical model for HIPping of Ti-6Al-4V powder is developed to improve model prediction by simulating powder filling and pre-consolidation by means of a two-dimensional Discrete Element Method (DEM). Particles’ dimension has been scaled up in order to reduce the computational cost of the analysis. An analytical model has been developed to calculate the relative density distribution from powder particle distribution provided by DEM, which is then passed in information to a three-dimensional FEM implementing the Abouaf and co-workers model for simulating powder densification during HIPping. Results obtained implementing the initial relative density distribution calculated from DEM are compared with those obtained considering a uniform relative density distribution over the powder domain (classic approach) at the beginning of the analysis. Experimental work has been carried out for validating the DEM (filling) and FEM (HIP) model. Comparison between experimental and numerical results shows the ability of the DEM model to represent the powder flow during filling and pre-consolidation, providing also a reliable values of the relative density distribution. It also highlights that taking into account the non-uniform powder distribution inside the canister prior HIP is vital to improve numerical results and produce near-net-shape components.     

基于任务同步及节能的实时调度算法*

实时任务在实际应用中通常需要以独占方式访问共享资源, 但是由于资源的独占性导致高优先权任务运行时往往被低优先权任务阻塞, 从而产生优先权反转, 难以满足任务的实时性;同时当前处理器由于较高的能量消耗,导致处理器热量散发提高及系统可靠性降低, 已经成为目前计算机领域较为关心的问题.提出一种基于任务同步及节能的实时调度算法CSSFA,有效地解决了上述难题.CSSFA在满足任务实时可调度性及任务同步的条件下,固定临界区的运行速度,使更多的空闲时间用于非临界区部分,有效地降低了整体系统的能耗;同时也能避免高优先权任务被阻塞、临界区继承高优先权任务的速度时所造成的处理器电压开关的频繁切换, 因而能有效地降低实时任务调度的成本.试验测试表明,CSSFA在调度性能上明显优于目前所知的有效算法.     

Effect of macerate enzymes on the yield,quality, volatile compounds and rheological property of prickly pear juice

Pectinase and cellulase enzymes were used to investigate efficacy for improving juice yield, stability and quality from prickly pear fruit. Pectinase improved the yield, stable color, color‐assayed as release of anthocyanins or carotinoids and clarity of the juice. A significant increase in the effectiveness of pectinase was observed as the concentration was increased from 0.05 to 0.50% v/w. However, at concentration >0.25% v/w they tended to impart a bitter flavor in the juice. Among three concentrations of pectinase and cellulase, pectinase at 0.50% v/w produced higher yield, a sediment‐free clear juice and high‐quality juice. The results indicated that depectinated clarified prickly pear juice behaves as a Newtonian fluid. It was found that the activation energy (Ea) for viscous flow was in the range of 5.02×10³–20.06×10³ kJ/mol depending on the concentrations of pectinase and cellulase enzyme treatment of prickly pear juice, in contrast to 22.15×10³ kJ/mol in untreated juice. Volatile compound concentrations of twelve compounds were not affected by pectinase and cellulase treatment. Overall the quality of prickly pear juice was better in pectinase‐treated juice compared with untreated and cellulase‐treated juice.     

Co-crystallization for enhanced dissolution rate of bicalutamide: preparation and evaluation of rapidly disintegrating tablets

Objectives: Enhance the dissolution rate of bicalutamide via co-crystallization with sucralose (sweetener), with the aim to develop rapidly disintegrating tablets with subsequent prompt dissolution.

Significance: Bicalutamide is antiandrogenic agent for the treatment of prostate cancer but has low and variable oral bioavailability, mainly attributed to poor dissolution. Co-crystallization with benign excipients is promising for dissolution enhancement with the additive serving dual functions. The benefit will become greater if dissolution enhancement is associated with the development of orodispersible tablets which is suitable for elderly patients who are the most vulnerable for prostate cancer.

Methods: Bicalutamide was dissolved in acetone in the presence of increasing molar ratios of sucralose. The solvent was evaporated while mixing to deposit crystals that were subjected to wet co-grinding until drying. The developed solids were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and X-ray diffraction in addition to monitoring bicalutamide dissolution.

Results: Instrumental analysis provided evidences for co-crystallization which was initiated at 1:1 molar ratio of bicalutamide to sucralose with complete co-crystallization at 1:4 molar ratio. The co-crystals provided faster bicalutamide dissolution compared with the unprocessed drug and that recrystalized from acetone in the absence of sucralose. The formulation containing bicalutamide with sucralose at 1:4 molar ratio was selected for tablet formulation into which superdisintegrants were included. The developed tablets exhibited flash disintegration with subsequent fast dissolution of bicalutamide.

Conclusions: The study introduced co-crystallization of bicalutamide with sucralose as an efficient tool to enhance the dissolution rate and to develop rapidly dissolving tablets for intraoral administration.     

Numerical simulation of single and dual pass conventional spinning processes

Due to the complex nature of sheet metal spinning processes, recent trends in analysis of the process are moving toward numerical techniques. These numerical methods, for instance finite element modelling, enable the study of parameters that can not easily be measured directly such as transient strains and stresses. Additionally, it allows a prediction of dynamic instabilities that may be used to control and achieve better product quality. In this investigation, a finite element dynamic explicit model has been used to simulate single and dual pass conventional spinning processes. The initial models are validated against published experimental data and show very good correlation. A variety of roller feed rates, roller passes and roller configurations are then simulated. Effects of roller feed rate on the axial force, radial force and thickness strain are established. The effect of roller pass and roller configuration on the axial force and thickness strain are also assessed.     

多处理器环境中基于节能及容错的实时动态调度算法

当前处理器由于较高的能量消耗,导致处理器热量散发的提高及系统可靠性的降低,同时任务实际运行中的错误也降低了系统的可靠性.因此同时满足节能性及容错性已经成为目前计算机领域较为关心的问题.提出的调度算法针对实时多处理器计算环境,以执行时间最短的任务优先调度为基础,结合其他有效技术(共享空闲时间回收及检查点技术),使得实时任务在其截止期内完成的同时,能够动态地降低整个系统的能量消耗及动态容错.针对独立任务集及具有依赖关系的任务集,提出两种算法:STFBA1及STFBA2(shortest task first based algorithm).通过实验与目前所知的有效算法相比,算法具有更好的性能(调度长度及能量消耗)及较低的通信时间复杂度.     

Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.