Crystalline Habit Research Articles

Crystal Engineering for Enhanced Solubility and Bioavailability of Poorly Soluble Drugs.

Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS). These techniques include; crystalline habit modification, polymorphism, solvates and hydrates, cocrystals, surface modification, crystallization, spherical agglomeration, liquisolid crystals and solid dispersions which are introduced and discussed in this review article. Each of these techniques has advantages and limitations which are emphasized on them.

Laboratory measurements of the sedimentation velocity of hexagonal planar ice crystals

New experimental measurements of the falling velocity, size and orientation of individual hexagonal plate‐like ice crystals are reported. The measurements were conducted at three different temperatures: −13, −16 and −20 °C. The diameter of the ice crystals measured in the experiments were between 50 μm and 250 μm, a size range which is in agreement with the size found in natural clouds. In this range, ice crystals show a random orientation during free fall and a falling velocity which increases with size. Results show that the fall velocity is insensitive to the temperature at which the ice crystals grow for the temperatures used in this study. An empirical power‐law between the Best and Reynolds numbers is presented using the capacitance as characteristic length and an estimation of the ice crystal mass. Despite the dispersion of the experimental data, the Best–Reynolds relationship found seems to be similar to the relationship for falling spheres in Stokes flow using the capacitance as the hydrodynamic radius. The fall velocities of hexagonal and columnar ice crystals were compared. The columnar ice crystals show a velocity larger than that of hexagonal ice crystals with the same value of capacitance. However, both crystalline habits show a unique empirical Be–Re relationship.

Crystal shape engineering and studies on the performance of vapour deposited InSe platelets

The influence of growth conditions on the morphology of stoichiometric indium monoselenide (InSe) crystals has been explored. Crystalline habits such as microfibres, needles, platelets and spherulites were obtained from physical vapour deposition by optimizing supersaturation, which sturdily depends on the temperature difference between charge (TC) and substrate (TS) zones ∆T, (= TC − TS). Morphology and growth mechanism were investigated with the aid of scanning electron microscopy and high-resolution transmission electron microscopy, which justified the layer by layer addition of atoms as per the Kossel–Stranski–Volmer model. Thermogravimetric measurements revealed the stability of InSe, confirming its melting point, M.P. = 611 °C, which reflects the formation of monophase. The mobility and carrier concentration calculated from the Hall effect experiment are found to be 11.14 cm2 V−1 s−1 and 1.52 × 1020 cm−3 respectively. Furthermore, optical characterizations such as UV–Vis–NIR and photoluminescence spectrometric analysis established the value of band gap as 1.45 eV, manifesting the versatility of the grown semiconducting platelets for photovoltaic applications.

Structure and Morphology of Poly(vinylidene fluoride) Nanoscrolls.

To date the scrolled morphology of γ-phase poly(vinylidene fluoride) (PVDF) has been witnessed via high temperature melt crystallization of crystalline thin films and through imaging of chemical etched PVDF bulk films. Here we show the first growth and characterization of free-standing γ-phase PVDF scrolls via solution crystallization. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy have been used to characterize and to further understand the fundamental preferred crystalline habit of the γ-phase of PVDF.

A Mechanistic Study of Phase Transformation in Perovskite Nanocrystals Driven by Ligand Passivation

Active control over the shape, composition, and crystalline habit of nanocrystals has long been a goal. Various methods have been shown to enable postsynthesis modification of nanoparticles, including the use of the Kirkendall effect, galvanic replacement, and cation or anion exchange, all taking advantage of enhanced solid-state diffusion on the nanoscale. In all these processes, however, alteration of the nanoparticles requires introduction of new precursor materials. Here we show that for cesium lead halide perovskite nanoparticles, a reversible structural and compositional change can be induced at room temperature solely by modification of the ligand shell composition in solution. The reversible transformation of cubic CsPbX3 nanocrystals to rhombohedral Cs4PbX6 nanocrystals is achieved by controlling the ratio of oleylamine to oleic acid capping molecules. High-resolution transmission electron microscopy investigation of Cs4PbX6 reveals the growth habit of the rhombohedral crystal structure is compos...

Albendazole nanocrystals: Optimization, spectroscopic, thermal and anthelmintic studies

Albendazole is a broad spectrum anthelmintic. Its efficacy is often limited by poor intestinal absorption mainly due to its low aqueous solubility. One of the best approaches to enhance aqueous solubility and dissolution of drug is nanoparticles. In the present study nanocrystals of albendazole were prepared by antisolvent precipitation technique followed by spray drying. The nanocrystals were optimized using 32 full factorial design considering stabilizer concentration and stirring speed as independent variable and dissolution efficiency as dependent variable. The prepared formulations were subjected for spectroscopic, thermal and dissolution studies. The results of FTIR showed that the drug was compatible with the excipients. The dissolution from nanocrystals was much more faster then pure albendazole. The particle size of nanocrystals was 277 nm. The XRD showed that there were no significant difference in the diffraction pattern of pure Albendazole and nanocrystals, crystalline habit modification happened in the nanocrystals. The lower melting point and enthalpy in physical mixture and in nanocrystals compare to pure Albendazole was reported in DSC study. TEM image of nanocrystals indicated rectangular nanoparticles. Gas chromatography study showed that the amount of residual solvent was less than the permissible limits. The optimized nanocrystals showed better anthelmintic activity compared to pure Albendazole.

Semiconducting Metal Oxide Nanostructures for Water Splitting and Photovoltaics

AbstractMetal oxide (MOx) semiconducting nanostructures hold the potential for playing a critical role in the development of a new platform for renewable energies, including energy conversion and storage through photovoltaic effect, solar fuels, and water splitting. Earth‐abundant MOx nanostructures can be prepared through simple and scalable routes and integrated in operating devices, which enable exploitation of their outstanding optical, electronic, and catalytic properties. In this review, the latest research results in this field are illustrated, highlighting the versatility of MOx nanostructures in meeting the stringent requirements to boost the efficiency of different systems. The functional properties inherently correlate to the morphology and the crystalline habit of MOx, which in most of the cases are organized in complex heterostructures. Tailoring the assembly of heterojunctions and their electronic band structure, the catalytic surface properties and the charge transport through complex networks represent the main challenge for the transition of MOx from the research to the real‐life in the field of energy conversion and storage.

Effect of laser irradiation on lithium niobate powders

LiNbO3 is a well-known material with high potential for many technological applications. However, conventional preparation techniques require high processing times at high temperatures. In this work, a new and fast approach is proposed, based on laser technology, envisaging obtaining bulk materials of LiNbO3. ´powders. The influence of the laser processing parameters, namely time and incident power beam, on the structure and morphology of the material was investigated and compared with the ones obtained from conventional heat treatment process.The results revealed a net dependence of LiNbO3 crystals’ morphology with both laser power and irradiation time. Increasing the time of irradiation new crystalline phases are promoted (Li3NbO4, Li0,585NbO3 and an “CaNb2O6” isostructural type), which were also detected on samples prepared by the conventional heat treatment process in an air-atmosphere furnace. Moreover, similar morphologies can be also obtained using conventional heat treatment and laser processing. The expected characteristics of LiNbO3 commercial powder (crystalline habit and size) were obtained for the based samples through laser irradiation under 6 W/1000s and through heat-treatments under 1000°C/24h. The laser processing proved to be a suitable technique to form LiNbO3 crystalline powders in a much more reduced time and also provides enough flexibility for tuning locally the grains size and morphology, allowing obtaining a morphological/structural radial gradient in a single step.

North-Seeking Magnetotactic Gammaproteobacteria in the Southern Hemisphere.

Magnetotactic bacteria (MTB) comprise a phylogenetically diverse group of prokaryotes capable of orienting and navigating along magnetic field lines. Under oxic conditions, MTB in natural environments in the Northern Hemisphere generally display north-seeking (NS) polarity, swimming parallel to the Earth's magnetic field lines, while those in the Southern Hemisphere generally swim antiparallel to magnetic field lines (south-seeking [SS] polarity). Here, we report a population of an uncultured, monotrichously flagellated, and vibrioid MTB collected from a brackish lagoon in Brazil in the Southern Hemisphere that consistently exhibits NS polarity. Cells of this organism were mainly located below the oxic-anoxic interface (OAI), suggesting it is capable of some type of anaerobic metabolism. Magnetosome crystalline habit and composition were consistent with elongated prismatic magnetite (Fe3O4) particles. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that this organism belongs to a distinct clade of the Gammaproteobacteria class. The presence of NS MTB in the Southern Hemisphere and the previously reported finding of SS MTB in the Northern Hemisphere reinforce the idea that magnetotaxis is more complex than we currently understand and may be modulated by factors other than O2 concentration and redox gradients in sediments and water columns. Magnetotaxis is a navigational mechanism used by magnetotactic bacteria to move along geomagnetic field lines and find an optimal position in chemically stratified sediments. For that, magnetotactic bacteria swim parallel to the geomagnetic field lines under oxic conditions in the Northern Hemisphere, whereas those in the Southern Hemisphere swim antiparallel to magnetic field lines. A population of uncultured vibrioid magnetotactic bacteria was discovered in a brackish lagoon in the Southern Hemisphere that consistently swim northward, i.e., the opposite of the overwhelming majority of other Southern Hemisphere magnetotactic bacteria. This finding supports the idea that magnetotaxis is more complex than previously thought.

Culture-independent characterization of novel psychrophilic magnetotactic cocci from Antarctic marine sediments.

Magnetotactic bacteria (MTB) are a heterogeneous group of ubiquitous aquatic microorganisms capable of biomineralizing nano-sized, membrane-bound, magnetic iron-rich mineral particles called magnetosomes. MTB are found in chemically-stratified aquatic sediments and/or water columns with a wide range of salinities, moderate to high temperatures, and pH varying from neutral to strongly alkaline. MTB from very cold environments have not been investigated to any great degree and here we characterize MTB from the low temperature Antarctic maritime region. Sediment samples were collected at nine sampling sites within Admiralty Bay, King George Island (62°23'S 58°27'W) from 2009 to 2013. Samples from five sites contained MTB and those from two of these sites contained large number of magnetotactic cocci that were studied using electron microscopy and molecular techniques. The magnetotactic cocci contained magnetosomes either arranged as two or four chains or as a disorganized cluster. The crystalline habit and composition of all magnetosomes analyzed with high-resolution transmission electron microscopy and energy dispersive X-ray microanalysis were consistent with elongated prismatic crystals of magnetite (Fe3 O4 ). The retrieved 16S rRNA gene sequences from magnetically-enriched magnetotactic cocci clustered into three distinct groups affiliated with the Alphaproteobacteria class of the Proteobacteria. Novel sequences of each phylogenetic cluster were confirmed using fluorescent in situ hybridization. Metagenomic data analysis of magnetically-enriched magnetotactic cocci revealed the presence of mam genes and MTB-specific hypothetical protein coding genes. Sequence homology and phylogenetic analysis indicated that predicted proteins are related to those of cultivated alphaproteobacterial MTB. The consistent and continuous low temperature of the sediment where the magnetotactic cocci are present (always below 1°C) suggests that these MTB from maritime Antarctica are psychrophiles. Moreover, similar morphotypes and 16S gene sequences were retrieved from samples collected from different sites from maritime Antarctica for several years suggesting that these new strains of MTB are indigenous members of Antarctic microbiota.

Smectite synthesis at low temperature and neutral pH in the presence of succinic acid

In some modern natural environments, authigenic clays occur in close spatial association with microbial cells and biofilms. These clays may be the result of a microbially influenced mineralization process. To test this hypothesis, we conducted laboratory experiments with organic molecules that are commonly produced by microbes and may promote mineral nucleation within biofilms. Solutions used for the experiments contained different organic acids (i.e., oxalic acid, succinic acid, citric acid, and EDTA), sodium silicate, and different cations (i.e., Al, Mg, Ca, K). The solutions, with a pH adjusted to 7, were incubated at 25°C for 2.5 or 6months. Precipitates showing a crystalline habit formed exclusively in the presence of succinic acid. In the other experiments, amorphous silica was the only precipitated phase. Transmission electron microscopy (TEM) observations including analytical electron microscopy (AEM) analyses and selected area electron diffraction (SAED) patterns indicate that the minerals formed in the presence of succinic acid are smectites with variable Al and Mg octahedral occupancy. Mg-rich smectites show a composition broadly similar to stevensite. Succinic acid is commonly produced by aerobic microbes as intermediate product of the tricarboxylic acid cycle. Thus, this biological degradation process might promote the formation of authigenic smectites in a large variety of natural environments. Our results may lead to a revised interpretation of some smectites present in ancient sedimentary rocks, which may have formed through a microbially influenced mineralization process similar to that simulated with our experiments.

Sustained Release Solid Dispersions of Pentoxyfylline: Formulation and Optimization

Objective: The purpose of the study is to formulate and optimize sustained release solid dispersions of pentoxyfylline using a combination of eudragit polymers and ethyl cellulose. Methods: Solid dispersions were formulated by solvent evaporation method.Preliminary batches were formulated using various drug to polymer ratio; with eudragit S100 and L100 (1:1 to 1:5 ratio), and with ethyl cellulose(1:1 to 1:3 ratio) and evaluated for solubility analysis. Based on results of preliminary batches, Box Behnken design was further applied and three factors (X1- concentration of Eudragit S100, X2- concentration of Eudragit L100, X3- concentration of Ethyl Cellulose) were selected with three levels (+1, 0, -1). Multiple linear regression was applied to generate polynomial equations and statistical evaluation. Prepared solid dispersions were investigated for sustained release properties via in vitro dissolution studies. Fourier transform infrared spectroscopic analysis (FTIR), X-ray diffraction analysis (X-RD), Differential scanning calorimetry (DSC) studies were carried out to evaluate drug polymer interactions. Scanning Electron Microscopy (SEM) analysis of optimized solid dispersion was carried out to evaluate surface morphology of the particles. Results: Batch F5 showed maximum sustained release (65.46% in 24 h) characteristics out of all solid dispersions. DSC studies indicated drug integrity when mixed with the polymeric carriers. FTIR and X-RD studies also ruled out any drug polymer interaction. A change in crystalline habit was observed in solid dispersion particles (F5 batch) as seen in SEM micrographs. Polynomial mathematical model generated using multiple regression analysis was found to be statistically significant (p<0.05). Conclusion: Release retarding effect was found to be dependent on polymer concentration. Therefore, an optimized combination may lead to better sustaining effect.

Electrical and mechanical properties of vapour grown gallium monotelluride crystals

The physical vapour deposition (PVD) of gallium monotelluride (GaTe) in different crystalline habits was established in the growth ampoule, strongly depending on the temperature gradient. Proper control on the temperatures of source and growth zones in an indigenously fabricated dual zone furnace could yield the crystals in the form of whiskers and spherulites. Optical and electron microscopic images were examined to predict the growth mechanism of morphologies. The structural parameters of the grown spherulites were determined by X-ray powder diffraction (XRD). The stoichiometric composition of these crystals was confirmed using energy dispersive analysis by X-rays (EDAX). The type and nature of electrical conductivity were identified by the conventional hot probe and two probe methods, respectively. The mechanical parameters, such as Vickers microhardness, work hardening index, and yield strength, were deduced from microindentation measurements. The results show that the vapour grown p-GaTe crystals exhibit novel physical properties, which make them suitable for device applications.

Design and Characterization of Microcrystals for Enhanced Dissolution Rate of Celecoxib

Poor aqueous solubility and bioavailability of drugs are one of the important factors affecting the absorption of drugs and consequently their therapeutic effectiveness. Celecoxib is a widely used anti-inflammatory agent, with special use in rheumatoid arthritis. It belongs to biopharmaceutical classification system (BCS) class II drug with low solubility and high permeability. The present study was aimed to prepare and characterize the microcrystals of celecoxib, employing in situ micronization technique by rapid solvent change approach to enhance the solubility and dissolution rate and to optimize the solvent and anti-solvent ratio (v/v) using hydrophilic stabilizers such as guar gum, maltodextrin and PVP K30. The prepared formulations were evaluated for percentage crystal yield, mean particle size, drug content and in vitro dissolution studies. Amongst the formulations prepared (F1-F9), F6 formulation containing maltodextrin as stabilizing agent at 0.1% w/v concentration with 1:6 ratio of solvent to anti-solvent (v/v) respectively was considered as optimized formulation in which percentage drug release was found to be 89.33% within 60 minutes in comparison with that of the pure drug dissolution of 30.26% only within 60 minutes. Characterization studies like SEM, DSC and XRD indicate the solubility enhancement of celecoxib microcrystals due to decrease in particle size when compared to that of pure drug. FT-IR spectroscopy studies revealed that there is no chemical interaction between the drug and stabilizer and crystalline habit modification occurs in the microcrystals without any polymorphic changes.

Colloidal Branched Semiconductor Nanocrystals: State of the Art and Perspectives

Colloidal inorganic nanocrystals are versatile nanoscale building blocks. Advances in their synthesis have yielded nanocrystals with various morphologies including spheres, polyhedra, rods, disks, sheets, wires, and a wide range of branched shapes. Recent developments in chemical methods have allowed the synthesis of colloidal nanocrystals made of sections of different inorganic materials connected together. Many research groups are investigating these nanocrystals' structural and photophysical properties experimentally and theoretically, and many have examined their prospects for commercial applications. Branched nanocrystals, in particular, are gaining attention, in part for their potential applications in solar cells or electronic devices. In this Account, we review recent developments in synthesis and controlled assembly of colloidal branched nanocrystals. Synthesis of branched nanocrystals builds on previous work with spherical nanocrystals and nanorods, but a unique factor is the need to control the branching event. Multiple arms can branch from a nucleus, or secondary branches can form from a growing arm. Branching can be governed by mechanisms including twinning, crystal splitting, polymorphism, oriented attachment, and others. One of the most relevant parameters is the choice of appropriate surfactant molecules, which can bind selectively to certain crystal facets or can even promote specific crystallographic phases during nucleation and growth. Also, seeded growth approaches recently have allowed great progress in the synthesis of nanocrystals with elaborate shapes. In this approach, nanocrystals with a specified chemical composition, size, shape, crystalline habit, and phase act as seeds on which multiple branches of a second material nucleate and grow. These approaches yield nanostructures with improved homogeneity in distribution of branch length and cross section. Ion exchange reactions allow further manipulation of branched nanocrystals by transforming crystals of one material into crystals with the same size, shape, and anion sublattice but with a new cation. Combining seeded growth with ion exchange provides a method for greatly expanding the library of branched nanocrystals. Assembly of morphologically complex nanocrystals is evolving in parallel to developments in chemical synthesis. While researchers have made many advances in the past decade in controlled assembly of nanocrystals with simple polyhedral shapes, modeling and experimental realization of ordered superstructures of branched nanocrystals are still in their infancy. In the only case of ordered superstructure reported so far, the assembly proceeds by steps in a hierarchical fashion, in analogy to several examples of assembly found in nature. Meanwhile, disordered assemblies of branched nanocrystals are also interesting and may find applications in various fields.

COMPARATIVE DIGITAL ANALYSIS OF DIFFERENT PHENYTOIN CRYSTAL HABITS

The purpose of this work was to evaluate the information obtained using some digital techniques for measuring the external form of pharmaceutical solids, employing a combination of several contour descriptors by means of classical and mathematics descriptors and a modified method of texture analysis technique based on Gray levels co-occurrence matrix. In this case, phenytoin was used as a model, because changing some conditions in the recrystallization process different crystalline habits were obtained. The evaluations of the measurements were performed using techniques of principal component analysis and hierarchical cluster analysis. Final analysis indicated that applying the texture technique Gray levels co-occurrence matrix measurement, the results were similar to those obtained by combining contour measurement with classical and mathematics descriptors techniques, therefore, as the texture method is faster and easier to implement, could be a good alternative for use in quality control of multisource pharmaceutical solid.

Electrochemical synthesis and characterization of hierarchically branched ZnO nanostructures on ensembles of gold nanowires

This study presents an electrosynthetic methodology to obtain hierarchically structured ZnO electrodes with improved surface area, by exploiting gold nanowires ensembles (3D-NEEs) as the growing substrate. By this way, semiconductor electrodes organized in the shape of fir-like branches are obtained. Branched nanofibres are characterized by electron microscopy and electron backscatter diffraction (EBSD), the latter technique allowing the determination of the crystalline habit of individual nanostructures. The hierarchical branched nanowires show enhanced performances with respect to water photooxidation in comparison with already known nanostructured materials such as 1D-ZnO nanowires.

Assisted-Hydrothermal Synthesis and Characterization of Flower-Like ZnO Nanostructures

Flower-like nanostructures formed by ZnO nanorods were synthesized and deposited on seeded silicon and glass substrates by a hexamethylenetetramine (HMTA) - assisted hydrothermal method at low temperature (90 oC) with methenamine ((CH3)6N4), as surfactant and catalyst. The substrates were seeded with ZnO nanoparticles. The structure and morphology of the nanostructures were studied by means of x-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), and scanning electron microscopy (SEM) techniques. Influence of the seed nanoparticle on the formation of the flower-like ZnO nanostructures is demonstrated. The influence of the organic oxygenated chains on the crystalline habit during the growth process is also observed.

Effect of Citric Acid on the Crystal Morphology of Gypsum and its Action Mechanism

Effects of citric acid on crystalline habit and crystal morphology of gypsum dihydrate were analyzed in great detail. The retarding mechanism of citric acid was also discussed from the standpoint of crystal growth by use of Scanning Electric Microscope and X-ray Photo Technology. The results shows that due to the complexion between citric acid and Ca2+, the initial supersaturation degree in liquid phase is greatly decreased, correspondingly the number of nuclei newly formed reduces and the growth rate of dihydrate slows down, so the crystal has enough time and space to grow, as a result, the crystal size becomes much larger in presence of citric acid. Citric acid is preferably adsorbed on c-axis which has the fastest growth rate and hinders its growth. Therefore the relative growth rate and crystal habit of various crystal faces are changed, consequently leading to the transformation of dihydrate crystal from need-like to short prismatic. Furthermore, the transformation is gradual as a function of citric acid addition, the higher the dosage, the larger the dihydrate crystal formed. After the addition of citric acid, the retarding effect produced and the reduction in strength of hardened gypsum paste are closely related with the variation of crystallization habit and crystal structure of hydration products.

The Isolation of the Toxic Principle of æNanthe Crocata

Summary A method is described for the preparation of highly toxic crystals from water dropwort root. Previous workers have only reported oils or resins of far less toxicity. These can be purified by recrystallisation, or by chromatography on an alumina column, when a single steel-grey zone is obtained. These purifications do not alter the melting point or the crystalline habit. The crystalline material, m.pt. 80° to 81° C., is insoluble in water, light petroleum, alkalis, and diluted mineral acids, but readily soluble in chloroform, ethyl alcohol and ether. The crystals are extremely unstable, yielding an insoluble infusible resinous material, with no pharmacological activity. If kept under nitrogen at 4°C., the crystals can be preserved for weeks with little loss of activity. Death after characteristic convulsions follows the intraperitoneal injection of an emulsion of the crystalline material into mice. The A.L.D. is 0°83 mg./kg. of body weight.