The 3-D model: Does time plasticity represent the influence of tableting speed?

The objective of this study is to test the hypothesis that time plasticity (parameterd from 3-D modeling) is influenced by tableting speed. Tablets were produced at different maximum relative densities (ϱ_rel,max) on an instrumented eccentric tableting machine and on a linear rotary tableting machine replicator. Some 3-D data plots were prepared using pressure, normalized time, and porosity according to Heckel. After fitting of a twisted plane, the resulting parameters were analyzed in a 3-D parameter plot. The materials used were dicalcium phosphate dihydrate (DCPD), spray-dried lactose, microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), κ-carrageenan (CAR), and theophylline monohydrate (TheoM). The results show that tableting speed especially influences the parameterd (time plasticity) of the 3-D model for plastically and viscoelastically deforming materials such as MCC, HPMC, CAR, and TheoM. For more plastically deforming materials such as MCC, HPMC, and TheoM, a subtle influence on ω is also visible. The stages of higher densification are affected more than the stages of lower densification. Brittle materials such as DCPD exhibit no influence of tableting speed. The influence of speed on spray-dried lactose is minor. The results are valid for data obtained from an eccentric tableting machine and also for data from a linear rotary tableting machine replicator. Thus, the empirically derived parameter time plasticityd really represents the influence of time.     

Comparison of the Halving of Tablets Prepared with Eccentric and Rotary Tablet Presses

The aim of this study was to compare the densification of powder mixtures on eccentric and rotary tablet presses and to establish relationships with the halving properties of the resulting scored tablets. This is an important problem because the recent guidelines of EU require verification of the equal masses of tablet halves. The models of Walker, Heckel, and Kawakita were used to describe the powder densification on the two machines. The calculated parameters revealed that the shorter compression cycle of rotary machines results in poorer densification and lower tablet hardness at a given compression force. This is manifested in poorer halving properties, which are influenced mainly by the hardness. Better densification improves the halving even at lower tablet hardness. This demonstrates that these parameters can be good predictors of tablet halving properties.     

Evaluation of powder and tableting properties of chitosan

The aim of this study was to analyze the process of tablet formation and the properties of the resulting tablets for 3 N-deacetylated chitosans, with a degree of deacetylation of 80%, 85%, or 90%. Material properties, such as water content, particle size and morphology, glass transition temperature, and molecular weight were studied. The process of tablet formation was analyzed by 3-D modeling, Heckel analysis, the pressure time function, and energy calculations in combination with elastic recovery dependent on maximum relative density and time. The crushing force and the morphology of the final tablets were analyzed. Chitosans sorb twice as much water as microcrystalline cellulose (MCC), the particle size is comparable to Avicel PH 200, a special type of MCC, the particles look like shells, and the edges are bent. Molecular weight ranges from 80 000 to 210 000 kDa, the glass transition temperature (Tg) was not dependent on molecular weight. The chitosans deform ductilely as MCC; however, plastic deformation with regard to time and also pressure plasticity are higher than for MCC, especially for Chit 85, which has the lowest crystallinity and molecular weight. At high densification, fast elastic decompression is higher. 3-D modeling allowed the most precise analysis. Elastic recovery after tableting is higher than for MCC tablets and continues for some time after tableting. The crushing force of the resulting tablets is high owing to a reversible exceeding of Tg in the amorphous parts of the material. However, the crushing force is lower compared with MCC, since the crystallinity and the Tg of the chitosans are higher than for MCC. In summation, chitosans show plastic deformation during compression combined with high elasticity after tableting. Highly mechanically stable tablets result. Published: September 8, 2006     

Use of First Derivative of Displacement vs. Force Profiles to Determine Deformation Behavior of Compressed Powders

Displacement (D) vs. force (F) profiles obtained during compaction of powders have been reported by several researchers. These profiles are usually used to obtain mechanical energies associated with the compaction of powders. In this work, we obtained displacement–force data associated with the compression of six powders; Avicel PH101, Avicel PH301, pregelatinized corn starch, anhydrous lactose, dicalcium phosphate, and mannitol. The first three powders are known to deform predominantly by plastic behavior while the later ones are known to deform predominantly by brittle fracture. Displacement–force data was utilized to perform in-die Heckel analysis and to calculate the first derivative (dD/dF) of displacement–force plots. First derivative results were then plotted against mean force (F′) at each point and against 1/F′ at compression forces between 1 and 20 kN. Results of the in-die Heckle analysis are in very good agreement with the known deformation behavior of the compressed materials. First derivative plots show that materials that deform predominantly by plastic behavior have first derivative values (0.0006–0.0016 mm/ N) larger than those of brittle materials (0.0004 mm/N). Moreover, when dD/dF is plotted against 1/F′ for each powder, a linear correlation can be obtained (R² = > 0.98). The slopes of the dD/dF vs. 1/F′ plots for plastically deforming materials are relatively larger than those for materials that deform by brittle behavior. It is concluded that first derivative plots of displacement–force profiles can be used to determine deformation behavior of powders.KEY WORDS: compression, deformation, first derivative     

Dry granulation and compression of spray-dried plant extracts

The purpose of this research was to evaluate the influence of dry granulation parameters on granule and tablet properties of spray-dried extract (SDE) fromMaytenus ilicifolia, which is widely used in Brazil in the treatment of gastric disorders. The compressional behavior of the SDE and granules of the SDE was characterized by Heckel plots. The tablet properties of powders, granules, and formulations containing a high extract dose were compared. The SDE was blended with 2% magnesium stearate and 1% colloidal silicon dioxide and compacted to produce granules after slugging or roll compaction. The influences of the granulation process and the roll compaction force on the technological properties of the granules were studied. The flowability and density of spray-dried particles were improved after granulation. Tablets produced by direct compression of granules showed lower crushing strength than the ones obtained from nongranulated material. The compressional analysis by Heckel plots revealed that the SDE undergoes plastic deformation with a very low tendency to rearrangement at an early stage of compression. On the other hand, the granules showed an intensive rearrangement as a consequence of fragmentation and rebounding. However, when the compaction pressure was increased, the granules showed plastic deformation. The mean yield pressure values showed that both granulation techniques and the roll compaction force were able to reduce the material's ability to undergo plastic deformation. Finally, the tablet containing a high dose of granules showed a close dependence between crushing strength and the densification degree of the granules (ie, roll compaction force). Published: October 14, 2005     

Preparation of Spherical Crystal Agglomerates of Naproxen Containing Disintegrant for Direct Tablet Making by Spherical Crystallization Technique

The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant.     

Physical mechanical and tablet formation properties of hydroxypropylcellulose: In pure form and in mixtures

The aim of the study was to analyze hydroxypropylcellulose (HPC) in pure form and in excipient mixtures and to relate its physical and chemical properties to tablet binder functionality. The materials used were Klucel hydroxypropylcellulose grades ranging from low to high molecular weight (80-1000 kDa) of regular particle size (250 microm mean size) and fine particle size (80 microm mean size). These were compared with microcrystalline cellulose, spray-dried lactose, and dicalcium phosphate dihydrate. Thermal behavior of HPC was analyzed by modulated temperature differential scanning calorimetry (MTDSC). Tablets of the pure materials and of dry blends with 4% low viscosity, fine particle HPC and 30% high viscosity, fine particle HPC were produced on an instrumented eccentric tableting machine at 3 relative humidities. The 3-dimensional (3-D) model with the parameters time plasticity d, pressure plasticity e, and the twisting angle omega, the inverse of fast elastic decompression was compared with the Heckel method for characterization of compaction. Elastic recovery and compactibility were also studied. The results show that HPC tablet formation is characterized by high plastic deformation. The d, e, and omega values were markedly higher as compared with the reference materials. Plasticity was highest for the fine particle size HPC types. Maximum compactibility was observed for low molecular weight, fine particle size HPC. Tableting of the mixtures showed deformation, which was strongly influenced by HPC. Plasticity and crushing force of formed tablets was increased. In conclusion, HPC is characterized by strong plastic deformation properties, which are molecular weight and particle size dependent.     

Direct Compression of Cellulose and Lignin Isolated by a New Catalytic Treatment

Tablet compression of softwood cellulose and lignin prepared by a new catalytic oxidation and acid precipitation method were investigated and compared with the established pharmaceutical direct compression excipients. Catalytic pretreated softwood cellulose (CPSC) and lignin (CPSL) were isolated from pine wood (Pinus sylvestris). The compaction studies were carried out with an instrumented eccentric tablet machine. The plasticity and elasticity of the materials under compression were evaluated using force-displacement treatment and by determining characteristic plasticity (PF) and elasticity (EF) factors. With all biomaterials studied, the PF under compression decreased exponentially as the compression force increased. The compression force applied in tablet compression did not significantly affect the elasticity of CPSC and microcrystalline cellulose (MCC) while the EF values for softwood lignins increased as compression force increased. CPSL was clearly a less plastically deforming and less compactable material than the two celluloses (CPSC and MCC) and hardwood lignin. CPSL presented deformation and compaction behaviour almost identical to that of lactose monohydrate. In conclusion, the direct tablet compression behaviour of native lignins and celluloses can greatly differ from each other depending on the source and isolation method used.     

Big Data to Knowledge: Application of Machine Learning to Predictive Modeling of Therapeutic Response in Cancer

BackgroundIn recent years, the availability of high throughput technologies, establishment of large molecular patient data repositories, and advancement in computing power and storage have allowed elucidation of complex mechanisms implicated in therapeutic response in cancer patients. The breadth and depth of such data, alongside experimental noise and missing values, requires a sophisticated human-machine interaction that would allow effective learning from complex data and accurate forecasting of future outcomes, ideally embedded in the core of machine learning design.ObjectiveIn this review, we will discuss machine learning techniques utilized for modeling of treatment response in cancer, including Random Forests, support vector machines, neural networks, and linear and logistic regression. We will overview their mathematical foundations and discuss their limitations and alternative approaches in light of their application to therapeutic response modeling in cancer.ConclusionWe hypothesize that the increase in the number of patient profiles and potential temporal monitoring of patient data will define even more complex techniques, such as deep learning and causal analysis, as central players in therapeutic response modeling.     

Effect of Particle Size on In-die and Out-of-die Compaction Behavior of Ranitidine Hydrochloride Polymorphs

The present study investigates the effect of particle size on compaction behavior of forms I and II of ranitidine hydrochloride. Compaction studies were performed using three particle size ranges [450–600 (A), 300–400 (B), and 150–180 (C) μm] of both the forms, using a fully instrumented rotary tableting machine. Compaction data were analyzed for out-of-die compressibility, tabletability, and compactibility profiles and in-die Heckel and Kawakita analysis. Tabletability of the studied size fractions followed the order; IB > IA > > IIC > IIB > IIA at all the compaction pressures. In both the polymorphs, decrease in particle size improved the tabletability. Form I showed greater tabletability over form II at a given compaction pressure and sized fraction. Compressibility plot and Heckel and Kawakita analysis revealed greater compressibility and deformation behavior of form II over form I at a given compaction pressure and sized fraction. Decrease in particle size increased the compressibility and plastic deformation of both the forms. For a given polymorph, improved tabletability of smaller sized particles was attributed to their increased compressibility. However, IA and IB, despite poor compressibility and deformation, showed increased tabletability over IIA, IIB, and IIC by virtue of their greater compactibility. Microtensile testing also revealed higher nominal fracture strength of form I particles over form II, thus, supporting greater compactibility of form I. Taken as a whole, though particle size exhibited a trend on tabletability of individual forms, better compactibility of form I over form II has an overwhelming impact on tabletability.     

Sequence classification with side effect machines evolved via ring optimization

The explosion of available sequence data necessitates the development of sophisticated machine learning tools with which to analyze them. This study introduces a sequence-learning technology called side effect machines. It also applies a model of evolution which simulates the evolution of a ring species to the training of the side effect machines. A comparison is done between side effect machines evolved in the ring structure and side effect machines evolved using a standard evolutionary algorithm based on tournament selection. At the core of the training of side effect machines is a nearest neighbor classifier. A parameter study was performed to investigate the impact of the division of training data into examples for nearest neighbor assessment and training cases. The parameter study demonstrates that parameter setting is important in the baseline runs but had little impact in the ring-optimization runs. The ring optimization technique was also found to exhibit improved and also more reliable training performance. Side effect machines are tested on two types of synthetic data, one based on GC-content and the other checking for the ability of side effect machines to recognize an embedded motif. Three types of biological data are used, a data set with different types of immune-system genes, a data set with normal and retro-virally derived human genomic sequence, and standard and nonstandard initiation regions from the cytochrome-oxidase subunit one in the mitochondrial genome.     

DNA polymerase programmed with a hairpin DNA incorporates a multiple-instruction architecture into molecular computing

Parallelism is one of the major advantages of molecular computation. A large number of data encoded in DNA molecules can be processed simultaneously by molecular biology techniques, although only a single set of instructions has been implemented in a solution. We have developed a computing machine, called the "whiplash" machine, which is made of DNA polymerase and a hairpin DNA. This machine simulates a finite state machine, executing its own instructions encoded in the DNA moiety, and would thus be applicable to multiple-instruction operation in a solution. In the present study, we explored the feasibility of this novel type of parallelism by applying the whiplash machine in a computation of the directed Hamiltonian path problem. The possible paths in a given graph were represented with different instruction sets, which were then implemented separately by whiplash machines in a test tube. After an autonomous operation of the machines, only the machine that implemented the instruction set corresponding to the Hamiltonian path was recovered from the tube. On the basis of the efficiency of machine operation, which was experimentally determined, 10(10) different instruction sets could be implemented simultaneously in a 1-ml solution.     

Effect of polymorphic form on the functional properties of cellulose: A comparative study

The powder and tableting properties of cellulose II powders (MCCII) and (SDCII) were evaluated and compared with common direct compression binders. The cellulose II polymorphs offered more benefits in terms of functionality as compared with cellulose I (Avicel^® PH-102) spray dried lactose and starch. Spray dried cellulose II (SDCII) had a better disintegrant ability, but a lower compactibility than microcrystalline cellulose I (Avicel^® PH-102). However, when mixed and compressed with acetaminophen, SDCII was as compactable as cellulose I. Further, unprocessed cellulose II has a comparable compressibility to that of cellulose I. SDCII was found to be less friable, less sensitive to magnesium stearate, and possessed better acetaminophen loading capacity than unprocessed cellulose II and comparable to that of cellulose I. The cellulose II materials showed potential for use as a direct compression excipient.     

3-D warped discrete cosine transform for MRI image compression

Image compression is an application of data compression on digital images. Several lossy/lossless transform coding techniques are used for image compression. Discrete cosine transform (DCT) is one such widely used technique. A variation of DCT, known as warped discrete cosine transform (WDCT), is used for 2-D image compression and it is shown to perform better than the DCT at high bit-rates. We extend this concept and develop the 3-D WDCT, a transform that has not been previously investigated. We outline some of its important properties, which make it especially suitable for image compression. We then propose a complete image coding scheme for volumetric data sets based on the 3-D WDCT scheme. It is shown that the 3-D WDCT-based compression scheme performs better than a similar 3-D DCT scheme for volumetric data sets at high bit-rates.     

基于小波变换的混合二维ECG数据压缩方法

提出了一种新的基于小波变换的混合二维心电(electrocardiogram,ECG)数据压缩方法。基于ECG数据的两种相关性,该方法首先将一维ECG信号转化为二维信号序列。然后对二维序列进行了小波变换,并利用改进的编码方法对变换后的系数进行了压缩编码:即先根据不同系数子带的各自特点和系数子带之间的相似性,改进了等级树集合分裂(setpartitioninghierarchicaltrees,SPIHT)算法和矢量量化(vectorquantization,VQ)算法;再利用改进后的SPIHT与VQ相混合的算法对小波变换后的系数进行了编码。利用所提算法与已有具有代表性的基于小波变换的压缩算法和其他二维ECG信号的压缩算法,对MIT/BIH数据库中的心律不齐数据进行了对比压缩实验。结果表明:所提算法适用于各种波形特征的ECG信号,并且在保证压缩质量的前提下,可以获得较大的压缩比。     

Crystallo-co-agglomeration: A novel technique to obtain ibuprofen-paracetamol agglomerates

The purpose of this research was to obtain directly compressible agglomerates of ibuprofen-paracetamol containing a desired ratio of drugs using a crystallo-co-agglomeration technique. Crystallo-co-agglomeration is an extension of the spherical crystallization technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or crystallization of a drug and its simultaneous agglomeration with another drug or excipient. Dichloromethane (DCM)-water system containing polyethylene glycol (PEG) 6000, polyvinyl pyrollidone, and ethylcellulose was used as the crystallization system. DCM acted as a good solvent for ibuprofen and bridging liquid for agglomeration. The process was performed at pH 5, considering the low solubility of ibuprofen and the stability of paracetamol. Loss of paracetamol was reduced by maintaining a low process temperature and by the addition of dextrose as a solubility suppressant. The agglomerates were characterized by differential scanning calorimetry, powder x-ray diffraction (PXRD), and scanning electron microscopy and were evaluated for tableting properties. The spherical agglomerates contained an ibuprofen-paracetamol ratio in the range of 1.23 to 1.36. Micromeritic, mechanical, and compressional properties of the agglomerates were affected by incorporated polymer. The PXRD data showed reduction in intensities owing to dilution and reduced crystallinity. Thermal data showed interaction between components at higher temperature. Ethylcellulose imparted mechanical strength to the agglomerates as well as compacts. The agglomerates containing PEG have better comparessibility but drug release in the initial stages was affected owing to asperity melting, yielding harder compacts. The agglomeration and properties of agglomerates were influenced by the nature of polymer.     

Automated classification of bird and amphibian calls using machine learning: A comparison of methods

We compared the ability of three machine learning algorithms (linear discriminant analysis, decision tree, and support vector machines) to automate the classification of calls of nine frogs and three bird species. In addition, we tested two ways of characterizing each call to train/test the system. Calls were characterized with four standard call variables (minimum and maximum frequencies, call duration and maximum power) or eleven variables that included three standard call variables (minimum and maximum frequencies, call duration) and a coarse representation of call structure (frequency of maximum power in eight segments of the call). A total of 10,061 isolated calls were used to train/test the system. The average true positive rates for the three methods were: 94.95% for support vector machine (0.94% average false positive rate), 89.20% for decision tree (1.25% average false positive rate) and 71.45% for linear discriminant analysis (1.98% average false positive rate). There was no statistical difference in classification accuracy based on 4 or 11 call variables, but this efficient data reduction technique in conjunction with the high classification accuracy of the SVM is a promising combination for automated species identification by sound. By combining automated digital recording systems with our automated classification technique, we can greatly increase the temporal and spatial coverage of biodiversity data collection.     

An approach for classification of highly imbalanced data using weighting and undersampling

Real-world datasets commonly have issues with data imbalance. There are several approaches such as weighting, sub-sampling, and data modeling for handling these data. Learning in the presence of data imbalances presents a great challenge to machine learning. Techniques such as support-vector machines have excellent performance for balanced data, but may fail when applied to imbalanced datasets. In this paper, we propose a new undersampling technique for selecting instances from the majority class. The performance of this approach was evaluated in the context of several real biological imbalanced data. The ratios of negative to positive samples vary from ~9:1 to ~100:1. Useful classifiers have high sensitivity and specificity. Our results demonstrate that the proposed selection technique improves the sensitivity compared to weighted support-vector machine and available results in the literature for the same datasets.     

Personal reflections on the nature of intelligence in humans and machines

Computers, the human mind, and social systems have common problems of inadequate memory and insufficient data manipulation speed. In each of these domains, information compression techniques have evolved to reduce storage and processing needs. Among the techniques for information compression, coding of information in procedures stands out as exceptionally powerful. Procedural information coding also gives rise to behavior that may be defined as intelligent. It is found in the human mind, in machines and in social systems. Its use in human thought is aided by language development which promotes regular review of abstract procedures. A practical consequence of better understanding of procedural information coding is the possibility of training people to exhibit greater mental capacity, a controversial possibility. This paper explores the impact of data processing resource limitations, data compression and procedural thinking in men and machines.