Non-crystalline State Research Articles

Ordered Mesoporous Silica Material SBA-15: A Broad-Spectrum Formulation Platform for Poorly Soluble Drugs

Encapsulating poorly soluble drugs in mesoporous silicates is an emerging strategy to improve drug dissolution. This study evaluates the applicability of the ordered mesoporous silicate SBA-15 as an excipient to enhance dissolution, for a test series of 10 poorly soluble compounds with a high degree of physicochemical diversity (carbamazepine, cinnarizine, danazol, diazepam, fenofibrate, griseofulvin, indomethacin, ketoconazole, nifedipine, and phenylbutazone). A generic solvent impregnation method was used to load all model compounds. The target drug content was 20%. The physical nature of the formulations was investigated using differential scanning calorimetry (DSC) and the pharmaceutical performance evaluated by means of in vitro dissolution. Aliquots of each formulation were stored at 25 degrees C/52% RH for 6 months, and again subjected to DSC and in vitro dissolution. The target drug content of 20% was attained in all cases. DSC data evidenced the noncrystalline state of the confined drugs. All SBA-15 formulations exhibited an enhanced dissolution as compared to their corresponding crystalline materials, and the high pharmaceutical performance of all formulations was retained during the 6 months storage period. The results of this study suggest that encapsulation in SBA-15 can be applied as a dissolution-enhancing formulation approach for a very wide variety of poorly soluble drugs.

In-Flight-Melted Soda-Lime-Silica Glass by RF Induction Thermal Plasma

Granulated raw materials with a particle size of 20–80 μm were prepared from a slurry of Na2CO3, CaCO3, and SiO2 (quartz) by the spray-dry method, and injected with carrier gas into a radio-frequency induction thermal plasma. Spherical particles 5–60 μm in size were obtained and analyzed. Thermo-gravimetric analysis and X-ray diffraction analysis showed that during the short flight of the order of milliseconds, all carbonates were decomposed and >95% quartz was reacted into a noncrystalline state. Glass transition was clearly observed by differential thermal analysis. Increase of the carrier gas from 3 to 6 L/min led to a decrease in the volatilization ratio of Na2O from 46% to 18% with a slight decrease of the reaction ratio of quartz in trade balance. Electron probe microanalysis showed that the volatilization could be attributed to an excess heating of small particles <30 μm, and suppression by the increase of carrier gas.

Temperature dependences of the density of borate glasses in equilibrium states at temperatures below the glass transition point

The kinetics of density relaxation during isothermal treatment of samples of vitreous boron oxide and sodium borate glasses (containing 15, 20, and 30 mol % Na2O) cooled from high temperatures and after heating of the samples stabilized at low temperatures is investigated over a wide range of temperatures below the glass transition point Tg. It is established that there exists a temperature Ts below which the density in the equilibrium state does not depend on the temperature, i.e., the temperature at which the supercooled liquid transforms into a new noncrystalline solid state. The distinguishing feature of this state is the absence of structural transformations after a change in the temperature. The temperatures of the transition of the supercooled liquid to the noncrystalline solid state and the ranges of lower temperatures at which the supercooled liquid can reach an equilibrium state within the limits of experimental error coincide with those previously obtained in the study of relaxation processes in these glasses by the small-angle X-ray scattering technique.

Preparation and Evaluation of Ketoprofen Hot-Melt Extruded Enteric and Sustained-Release Tablets

Hot-melt extruded tablets with enteric and sustained-release properties were prepared using ketoprofen as a model drug and Eudragit® L100 as the carrier. Ketoprofen, with a similar solubility parameter to Eudragit® L100, was homogeneously dispersed in the polymer matrix in a non-crystalline state, and was identified by differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy analysis. To compare the enteric and sustained-release characteristics, tablets of physical mixtures and comminuted extrudates were also produced with a tensile strength of 5.0 kg/cm2. The drug release percentage was below 3% in 0.1 M HCl and a sustained release for 6 to 12 hours was obtained with the tablets prepared by direct cutting of the extrudates and by compressing the pulverized extrudates, while no enteric and sustained-release properties were exhibited by the physical mixture tablets. The release mechanisms of the two types of tablets from their extrudates were different only because of their porosity. For the cut tablets, the drug was released according to the erosion mechanism, whereas in the extruded tablets the release property was controlled by erosion and diffusion mechanisms simultaneously.

Synthesis and characterization of ultrafine Ni–Co composite powder by freeze-drying

Abstract This research focused on the synthesis of ultrafine Ni–Co composite powder prepared using a freeze-drying technique. In the process of freeze-drying, the Ni–Co powder was prepared by freeze-drying the precursor from simple NiC 2 O 4 and CoC 2 O 4 powders. Thermal decomposition of the amorphous freeze-dried precursor powder produced the ultrafine Ni–Co composite powder. To assure process control and product characterization, the freeze-dried precursor and the final products were analyzed by means of XRD, SEM, TEM, and IR. The results showed that the freeze-dried powder existed in a non-hygroscopic and non-crystalline state. The final product of the experiments was a Ni–Co composite powder, which existed in the form of a single crystalline state and represented fine, homogeneous, spherical particles, reaching a size range of approximately 40–70 nm. The freeze-dried powder was composed of [Ni(NH 3 ) 6 ] 2+ and [Co(NH 3 ) 6 ] 3+ .

Preparation and Properties of BN-SiO&lt;sub&gt;2&lt;/sub&gt; Composite Ceramics

A series of BN-SiO2 composite ceramics with high relative densities have been fabricated by hot pressing of a mixture of hexagonal boron nitride powder and silica sol. X-ray diffraction (XRD) results show that silica are distributed in the BN matrix as noncrystalline state. Microstructure of as-sintered composite ceramics is observed by scanning electron microscopy (SEM). The influence of the secondary phase on the mechanical properties is studied by varying the silica content from 10 wt% up to 40 wt%. Dielectric properties of composite ceramics are also measured from 1 MHz to 2.0 GHz.

Glass Transitions of Ordinary and Heavy Water within Silica‐Gel Nanopores

The dynamic properties of water confined within nanospaces are of interest given that such water plays important roles in geological and biological systems. The enthalpy-relaxation properties of ordinary and heavy water confined within silica-gel voids of 1.1, 6, 12, and 52 nm in average diameter were examined by adiabatic calorimetry. Most of the water was found to crystallize within the pores above about 2 nm in diameter but to remain in the liquid state down to 80 K within the pores less than about 1.6 nm in diameter. Only one glass transition was observed, at T(g) = 119, 124, and 132 K for ordinary water and T(g) = 125, 130, and 139 K for heavy water, in the 6-, 12-, and 52-nm diameter pores, respectively. On the other hand, two glass transitions were observed at T(g) = 115 and 160 K for ordinary water and T(g) = 118 and 165 K for heavy water in the 1.1-nm pores. Interfacial water molecules on the pore wall, which remain in the noncrystalline state in each case, were interpreted to be responsible for the glass transitions in the region 115-139 K, and internal water molecules, surrounded only by water molecules in the liquid state, are responsible for those at 160 or 165 K in the case of the 1.1-nm pores. It is suggested that the glass transition of bulk supercooled water takes place potentially at 160 K or above due to the development of an energetically more stable hydrogen-bonding network of water molecules at low temperatures.

Effect of Solvent on Morphological and Structural Change of Cellulose under Ball-Milling

Cellulose derived from cotton was ball-milled with some hydrophilic and hydrophobic solvents such as water, toluene, 1-butanol and also without solvent (dry state), and effect of the solvents on morphological and structural changes of the cellulose were investigated. The original fibrous cellulose was changed to the aggregated globular particles by water and dry state ball-milling, plate-like particles by toluene processing, and a mixture of rugged globular particles and plate-like particles by 1-butanol processing. The globular particles prepared without solvent showed fairly low crystallinity and their inter- and intra-molecular hydrogen bonds were deformed, leading to an increase in free hydroxyl groups. The globular particles prepared with water exhibited a mixture of crystalline structure as cellulose I, cellulose II and non-crystalline state. In the case of the products with toluene, the plate-like particles significantly retained their original crystalline structure and hydrogen bonds. The 1-butanol processing seems to give the particles consisting of cellulose I and small amounts of either non-crystalline or cellulose II. The cellulose/dye stuff mixtures under the presence of the above solvents were prepared using 4-aminoazobenzene to investigate the differences in the surface property of the particles prepared by the ball-milling processing. Characteristic color development of each cellulose particles was clearly distinguished depending on the effect of the solvent (cinnabar; without solvent, yellow; toluene and yellowish-green; water or 1-butanol).

On liquid polymorphism and liquid–liquid phase transitions

Liquids are not just amorphous phases as commonly believed. It is pointed out that recentpioneering work on liquid phase transitions has shed new light on the phase behaviour ofmatter in the non-crystalline state.

Structural ordering and ice-like glass transition on cooling the nano-channel water formedwithin a crystalline framework

Heat capacities and enthalpy relaxation rates were measured for crystalline[Ni(cyclam)(H2O)2]3(TMA)2·24H2O,where cyclam is 1,4,8,11-tetraazacyclotetradecane, TMA is 1,3,5-benzene tricarboxylic acid, and24H2O represents the water forming a nano-channel. A phase transition was found to occur at196.9 K, and a glass transition at 87 K. A potential picture is given for the progress of theordering of water molecules and hydrogen atoms in the channel. At room temperature,interfacial water molecules form hydrogen bonds with the oxygen atoms of the channelwall, and the aggregation of water molecules is recognized, as the average structure,to be in a crystalline state with a long-range order. The bond formation playsimportant role in the stabilization of the crystalline framework with a channelstructure. The aggregate transforms to a more stable crystalline state at 196.9 K.All the water molecules should be fixed completely there. The positions of thehydrogen atoms on the network are, however, essentially in the disordered statewhile keeping an ice rule, and freeze at 87 K only with a short-range order in thearrangement. The progress of such ordering of channel water reveals a strikingcontrast to the behaviour of the water within meso-porous silicas, in which themolecules in the interface are always in the non-crystalline state and those in the porecentre tend to crystallize only when the pore diameter is greater than 2 or 3 nm.

A phosphoryl transfer intermediate in the GTPase reaction of Ras in complex with its GTPase-activating protein.

The hydrolysis of nucleoside triphosphates by enzymes is used as a regulation mechanism in key biological processes. Here, the GTP hydrolysis of the protein complex of Ras with its GTPase-activating protein is monitored at atomic resolution in a noncrystalline state by time-resolved FTIR spectroscopy. At 900 ms, after the attack of water at the gamma-phosphate, there appears a H2PO4- intermediate that is shown to be hydrogen-bonded in an eclipsed conformation to the beta-phosphate of GDP. The H2PO4- intermediate is in a position where it can either reform GTP or be released from the protein in 7 s in the rate-limiting step of the GTPase reaction. We propose that such an intermediate also occurs in other GTPases and ATPases.

In vitro and in vivo evaluation of carbamazepine-loaded enteric microparticles

The objective of the study was to prepare and evaluate carbamazepine-loaded enteric microparticles produced by a novel coacervation method. An aqueous polymeric stabilizer solution was added to an organic carbamazepine/Eudragit ® L100-55 solution. Water, which is a non-solvent for the drug and the enteric polymer, caused phase separation and the formation of coacervate droplets. These droplets hardened into microparticles upon further addition of the aqueous phase. The microparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency, yield, physical state and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Microparticles with a smooth surface and dense structure were obtained with high encapsulation efficiency (>85%) and yield (>90%). The drug was in a non-crystalline state in the matrix and physically stable for 5 months at room temperature. Under sink conditions, the drug dissolution rate from the microparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the microparticles was stable after 5 months. Under non-sink conditions, an unstable supersaturated solution of carbamazepine was obtained from microparticles with the subesequent formation of needle-shaped crystals. The high surface area and good wettability of the microparticles, the non-crystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the microparticles when compared to the physical mixture.

Effects of thermal processing and fruit matrix on β-carotene stability and enzyme inactivation during transformation of mangoes into purée and nectar

Effects of thermal mango processing on β-carotene stability and inactivation of peroxidase (POD) and polyphenol oxidase (PPO) were systematically evaluated on a laboratory scale, mimicking typical operations in continuous and small-size batch production of mango purée. Treatments comprised pasteurisation between 85 and 93 °C up to 16 min of holding time, with pasteurisation values ( P T ref = 93.3 ° C z = 8.9 ° C ) of 0.34–14.91 min, and thermal routines usually applied in enzymatic maceration for pectin degradation to standardise mango pulp viscosity. Although significant trans– cis-isomerisation of β-carotene ( P < 0.05) was shown by the formation of 13- cis-β-carotene, maximum vitamin A loss during pasteurisation of mango purée did not exceed 15.4%, owing to a total β-carotene retention of 93%. PPO was readily inactivated after 1 min, whereas residual POD activities of 4.0–6.3% were detected, even after 16 min, at all pasteurisation temperatures. To study the influence of the fruit matrix during pasteurisation, β-carotene stability was additionally evaluated at modified physical states in aqueous and in oil-in-water (o/w) emulsified model preparations. After disintegration of the mango matrix, trans– cis-isomerisation was higher than in model preparations, indicating a non-crystalline state of β-carotene in the mango mesocarp. In semi-continuous production of mango nectar on a pilot-plant scale, evaluated by stepwise process control, four heating treatments used for steam peeling, thermal inactivation of endogenous enzymes prior to enzymatic pulp liquefaction, and pasteurisation of purée and nectar, respectively, consistently resulted in a final retention of 83% of the vitamin A value of the fruit dry matter.

Encapsulation of lipophilic drugs within enteric microparticles by a novel coacervation method

Enteric microparticles were prepared by a novel microencapsulation method in order to improve the oral bioavailability of lipophilic drugs. This method involved the addition of an aqueous polymer solution to an organic enteric polymer solution containing lipophilic drugs. In contrast to classical coacervation microencapsulation methods, the drugs were initially also dissolved and not dispersed in the organic polymer solution. The hydrophilic polymer (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC) and Poloxamer 407) was dissolved in the aqueous phase and acted as a stabilizer for the coacervate droplets, preventing their coalescence and leading to the formation of enteric microparticles. The size of the enteric microparticles decreased with higher concentrations of the hydrophilic polymers, a higher pH of the aqueous polymer solution, a higher content of carboxyl groups of the enteric polymer and with better polymer solvents. Amide-containing lipophilic drugs, such as carbamazepine, lidocaine and cyclosporine A, were successfully encapsulated in the enteric microparticles in a non-crystalline state and were physically stable for 5 months. The high solubility of carbamazepine in the enteric polymer (>30%, w/w), a high partition coefficient between polymer-rich/-poor regions and strong drug/polymer interactions contributed to the high drug encapsulation efficiency (90%, w/w). In contrast, carboxyl-containing drugs (indomethacin, ibuprofen) and hydroxyl-containing drug (17β-estradiol hemihydrate) crystallized inside or outside the polymeric matrix due to their low solubility in the enteric polymer.

The influence of water on the structure and glass transition of sodium borate supercooled liquids from the small-angle X-ray scattering data

Sodium borate glasses containing 5.5, 15, and 25 mol % Na2O are synthesized under different conditions (different temperatures and times of heat treatment, treatment under vacuum) and studied by the small-angle X-ray scattering (SAXS) technique. The temperatures of the glass transition and the transition from the supercooled liquid state to the noncrystalline solid state are determined from the temperature dependences of the SAXS intensity. It is revealed that a decrease in the water content leads to an increase in the glass transition temperatures and to an increase in the SAXS intensity in the case of glasses containing 15 and 25 mol %. It is assumed that this behavior can be associated with the increase in the isothermal compressibility.

Specific features of the kinetics of structural relaxation in microinhomogeneous glasses

The kinetics of structural relaxation in vitreous boron oxide and sodium borate glass containing 5.5 mol % Na2O during isothermal treatment at a number of temperatures after cooling from high temperatures and a sharp increase in the temperature of samples stabilized at T < Tg for different times is studied by the small-angle X-ray scattering (SAXS) technique. It is shown that, as the fictive temperature of samples approaches the temperature at which the supercooled liquid transforms into a noncrystalline solid state, the times of development of a structural inhomogeneity that arises in the samples after a drastic increase in the temperature increase considerably in a narrow temperature range (1–2 K). The intensity of small-angle X-ray scattering by a micro-inhomogeneous structure formed in the course of relaxation processes in chemically inhomogeneous glasses substantially exceeds the SAXS intensity observed during structural relaxation of vitreous boron oxide. This is associated with the increase in the sizes of structural inhomogeneity regions in the matrix in heterogeneous samples as compared to the sizes of similar regions in homogeneous glasses. Stresses arising in heterogeneous samples during structural relaxation are responsible for the interference effects that substantially affect both the SAXS intensity at angles close to zero and, correspondingly, the light scattering intensity.

Aperiodic core structures of Pd and Pt giant clusters chemically stabilized with diphenyl phosphide ligands

Atomic scale structures and compositions of “giant” clusters [Pd 2(PPh 2)H x ] n , ( I) and [Pt(PPh 2)] n ( II) (PPh 2 = diphenyl phosphide, n ≅ 6–10) and Pd∼ 561Phen∼ 60(OAc)∼ 180 ( III) (Phen = 1,10-phenanthroline; OAc = CH 3COO −) have been investigated by high-resolution electron microscopy, electron diffraction and integrated field-emission analytical electron microscopy combining high-angle annular dark-field scanning transmission electron imaging, electron energy-loss spectroscopy (EELS) and windowless energy-dispersive X-ray nanoanalyses of metal cores and ligand shells. Observations revealed a uniform cell structure of the cluster matter with the unimodal core size distributions. Compositional deviations from the ideal stoichiometry were determined by EELS line profile analyses starting at the interfaces between cluster ( I) cores and ligand shells. For clusters ( I) and ( II), with core sizes centered around 1.6 ± 0.3 nm and 1.5 ± 0.3 nm, respectively, lattice fringes and Debye–Scherrer diffraction rings were not observed, thus indicating that the structure within particles is not periodic. This was in contrast with the sputtered reference 1–2 nm Pt particles, which show clear evidence of crystallinity. Polyhedral Pd cores of clusters ( III) with the diameter of 2.4 ± 0.3 nm also revealed lattice fringes assigned to an expanded face-centered cubic (fcc) structure, sometimes with multiple twinning. The structural differences suggest a ligand induced metal-to-molecular (non-crystalline) state transformation in clusters ( I) and ( II).

Chemical and Structural Properties of Drug–protein Nanocomposites Prepared by Pulsed Laser Deposition from Conjugated Targets

Nanostructured indomethacin (IM) – bovine serum albumin (BSA) composite particulates below 50 nm were obtained by pulsed laser deposition (PLD) with 1064 nm IR beam. IM and BSA powders were coground for up to 210 min to prepare conjugated targets for PLD with varying structural states. The ablation threshold was determined to be around 1.8 J/cm2, from in situ monitoring of the deposited amount by a QCM sensor. The crystallinity of IM was preserved after PLD at 5 J/cm2 and decreased with increasing the laser fluence. The non-crystalline state of IM in the target after prolonged cogrinding with BSA, was also preserved in the deposited film. FT-IR absorption bands due to amide I of BSA became sharper while preserving the peak top position after cogrinding with IM. Conversely, we observed broadening of the amide I bands by PLD. Preservation and change in the chemical and structural states of the conjugates after PLD is discussed in terms of the secondary structure of BSA and crystallinity of IM.

Contact Angle of Poly(alkyl methacrylate)s and Effects of the Alkyl Group

The contact angle (θ) of water on the surface of various poly(alkyl methacrylate)s was measured in order to obtain a relationship between the chain length of the alkyl group and the surface energy of the polymers, where the alkyl is an n-CnH2n+1 (n = 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20) group and a phytanyl or (3RS,7RS,11RS)-3,7,11,15-tetramethylhexadecyl group. Generally, the plotting of θ vs alkyl chain length gave a bell-shaped curve to show the maximum θ at a certain poly(alkyl methacrylate). The θ of each polymer, however, varied characteristically with temperature; hence, the polymer providing the maximum θ was altered to another polymer by changing temperature. The complex phenomenon was analyzed by the means of DSC, ESCA, XRD, and RAS IR spectra, etc. of the polymers to reveal that the contact angle was dramatically enhanced when the polymer state was changed to a noncrystalline (melt) state from a crystalline state. In other words, the polymer, which possesses long alkyl groups with random ...

Preparation and characterization of nanopowder for emission materials by freeze-drying

Nanopowder of rare earth tungsten for emission materials was prepared by freeze-drying process. The solution of ammonium metatungstate with rare earth nitrate was quench-frozen and dried in vacuum to produce the mixture of ammonium metatungstate and rare earth nitrate powder with high purity. Most of the powder existed in non-hygroscopic and non-crystalline state. During the experiment, the advantage of freeze-drying process was successfully achieved. High speed freezing also fixed the ion distribution that once formed in the solution. Due to less atomic moves during the subsequent sublimation process, the homogeneity of the original solution was retained. The freeze-dried compound, which consisted of ammonium metatungstate and rare earth nitrate, was reduced under various conditions to determine the effect of reaction conditions (temperature and time) on the particle size of the final rare earth tungsten powder. Experiments showed that the grain size of the powder mixture depended on the temperature and duration of the reduction process. The characterization of the powder mixture, microcompact and pellets were analyzed by means of XRD, FESEM and TEM throughout the whole experimental process.