Preparation and characterization of solid dispersions of piroxicam with hydrophilic carriers

The objective of this study was to improve the dissolution rate of a poor water soluble drug, piroxicam, by solid dispersion technique. Solid dispersions were prepared by three different methods depending on the type of carrier. The dissolution rate of piroxicam was markedly increased in solid dispersion of myrj 52, Eudragit^® E100 and mannitol. Solubility studies revealed a marked increase in the solubility of piroxicam with an increase in myrj 52 and Eudragit^® E100 concentrations. Data from the X-ray diffraction and FT-IR spectroscopy showed that piroxicam was amorphous in the solid dispersions prepared with dextrin and Eudragit^® E100.     

Characterization and dissolution properties of ketoprofen in binary and ternary solid dispersions with polyethylene glycol and surfactants

The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has been investigated. Physicochemical and morphological properties of the various solid systems were determined by differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction analysis, and scanning electron microscopy. The results from dissolution studies, performed according to the USP 24 basket method, indicated that all ternary dispersed systems were significantly (p < 0.001) more efficacious than the corresponding binary ones, by virtue of the additive wetting and solubilizing effect due to the presence of the surfactant. The relative effectiveness of the incorporated surfactant was in the same order as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the solid dispersion preparation method, coevaporated products always gave better results than the corresponding cofused ones; however, this effect was statistically significant (p < 0.001) only in the initial phase of the dissolution process. The most effective solid dispersion was the 10-80-10 w/w drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary coevaporate) and dissolution of about 100% drug after 30 min (in comparison with > 120 min for the binary coevaporate).     

Thermal behavior and dissolution properties of naproxen from binary and ternary solid dispersions

Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000, 6000, or 20,000) as a carrier with or without incorporation of anionic (sodium dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by the melting method. Physicochemical characteristics were determined by differential scanning calorimetry (DSC) and X-ray diffraction analysis. The results of dissolution studies showed that drug dissolution properties were better from ternary systems than from binary systems since in the former the wetting and solubilizing effects of surfactant and polymer were additive. No influence of the PEG molecular weight was found. The best performance given by anionic surfactant has been attributed to several factors, such as higher hydrophilicity, better solubilizing power, and most facile interaction with both drug and PEG. No important changes in solid-state characteristics or in drug dissolution properties were found after 30 months storage for dispersions with or without surfactant. Only a slight decrease in initial drug dissolution rate was observed at the highest concentration (10% w/w) of SDS.     

The rare-earth doping of binary and ternary chalcogenides

Experimental evidence on the rare-earth doping of the IIVI compounds and a knowledge of the rare-earth chalcogenide structures is used to suggest a set of principles with which to predict the ultimate doping limit for the binary and ternary chalcogenides. The validity of these rules is tested by experiment.     

Superconductivity of some binary and ternary transition-metal borides

Superconducting transition temperatures of some binary transition-metal borides and a new series of ternary transition-metal borides are reported. The variation of T_C vs electron/atom ratio and the crystal chemical behavior of the borides in relation to their superconducting behavior are discussed.     

Magnetostriction of binary and ternary Fe–Ga alloys

This article will review the development of the Fe–Ga (Galfenol) alloy system for magnetostriction applications including work on substitutional ternary alloying additions for magnetic property enhancement. A majority of the alloying addition research has focused on substitutional ternary elements in Bridgman grown single crystals with the intent of improving the magnetostrictive capability of the Galfenol system. Single crystals provide the ideal vehicle to assess the effectiveness of the addition on the magnetostrictive properties by eliminating grain boundary effects, orientation variations, and grain-to-grain interactions that occur when polycrystals respond to applied magnetic fields. In almost all cases, ternary additions of transition metal elements have decreased the magnetostriction values from the binary Fe–Ga alloy. Most of the ternary additions are known to stabilize the D0₃ chemical order and could be a primary contribution to the observed reduction in magnetostriction. In contrast, both Sn and Al are found to substitute chemically for Ga. For Sn additions, whose solubility is limited, no reduction in magnetostriction strains are observed when compared to the equivalent binary alloy composition. Aluminum additions, whose effect on the magnetoelastic coupling on Fe is similar to Ga, result in a rule of mixture relationship. The reviewed research suggests that phase stabilization of the disordered bcc structure is a key component to increase the magnetostriction of Fe–Ga alloys.     

Limits of recognition for binary and ternary vapor mixtures determined with multitransducer arrays

The discrimination of simple vapor mixtures from their components with polymer-coated multitransducer (MT) arrays as a function of the absolute and relative concentrations of those components is explored. The data set consists of calibrated responses to 11 organic vapors from arrays of 5 or 8 microsensors culled from a group of 5 cantilever, 5 capacitor, and 5 calorimeter transducers coated with 1 of 5 different sorptive-polymer films. Monte Carlo methods are applied to simulate error-enhanced composite responses to all possible binary and ternary mixtures of the 11 vapors, and principal component regression models are established for estimating expected rates of recognition as a function of mixture composition. The limit of recognition (LOR), defined as the maximum recognizable mixture composition range, is used as the metric of performance. With the optimal 8-sensor MT array, 19 binary and 3 ternary mixtures could be identified (i.e., discriminated from their components) with <5% error. The binary-mixture LORs are shown to decrease with increases in the baseline noise levels and random sensitivity variations of the sensors, as well as the similarity of the vapors. Importantly, most of the binary LOR contours are significantly asymmetric with respect to composition, and none of the mixtures could be recognized with <5% error at component relative concentration ratios exceeding 20:1. Discrimination of ternary mixtures from their components and binary subcomponent mixtures is possible only if the relative concentration ratio between any two of the components is <5:1. In comparing binary LORs for the best five-sensor single-transducer (ST) array to those of the best five-sensor MT array, the latter were larger in nearly all cases. The implications of these results are considered in the context of using such arrays as detectors in microanalytical systems with upstream chromatographic modules.     

Friction and wear characteristics of binary and ternary zirconia ceramics

The friction and wear behaviour of binary and ternary zirconia ceramics was studied in an unlubricated environment over a range of loads and sliding speeds. In these tests, ternary zirconia ceramics based on the ZrO₂-CeO₂-Y₂O₃ system were seen to show very low friction coefficients and wear rates compared with the other binary zirconia systems investigated, with a coefficient of friction typically about 50% that of other (binary) zirconia ceramics, and a wear rate of about 1% of that of tetragonal yttria-doped zirconia. During slide testing of zirconias a transition from a low wear regime to a high wear regime was observed with increasing sliding velocity and load. SEM was used to identify the wear mechanisms.     

Effect of water-soluble carriers on dissolution characteristics of nifedipine solid dispersions

Solid dispersions of nifedipine (NP) with polyethylene glycols (PEG4000 and PEG6000), hydroxypropyl-β-cyclodextrin (HPβCD), and poloxamer 407 (PXM 407) in four mixing ratios were prepared by melting, solvent, and kneading methods in order to improve the dissolution of NP. The enhancement of the dissolution rate and the time for 80% NP dissolution T_80% depended on the mixing ratio and the preparation method. The highest dissolution rate and the T_80% as short as 15 min were obtained from PXM 407 solid dispersion prepared by the melting method at the mixing ratio of 1:10. The X-ray diffraction (XRD) patterns of solid dispersions at higher proportions of carriers demonstrated consistent with the results from differential scanning calorimetric (DSC) thermograms that NP existed in the amorphous state. The wettability and solubility were markedly improved in the PXM 407 system. The presence of intermolecular hydrogen bonding between NP and PEGs and between HPβCD and PXM 407 was shown by infrared (IR) spectroscopy.     

Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media

Abstract

The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25?°C and 37?°C) were investigated in this work.

Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions.

All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25?°C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37?°C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures.

Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25?°C may not predict the supersaturation behavior at physiologically relevant temperatures.     

A general approach to binary and ternary hybrid nanocrystals

We describe and demonstrate a general strategy for engineering binary and ternary hybrid nanoparticles based on spontaneous epitaxial nucleation and growth of a second and third component onto seed nanoparticles in high-temperature organic solutions. Multifunctional hybrid nanoparticles that combine magnetic, plasmonic, and semiconducting properties and that are tunable in size and morphology can be realized, as demonstrated for combinations of Au, Fe3O4 and PbS or PbSe. The properties of each component within the hybrids can be modulated strongly by the conjugating component(s) aided by the coherent interfaces between them.     

Properties of self-compacting mortars with binary and ternary cementitious blends of fly ash and metakaolin

The link between flow properties and the formulation is actually one of the key-issues for the design of self-compacting concretes (SCC). As an integral part of a SCC, self-compacting mortars (SCMs) may serve as a basis for the design of concrete since the measurement of the rheological properties of SCCs is often impractical due to the need for complex equipment. This paper discusses the properties of SCMs with mineral admixtures. Portland cement (PC), metakaolin (MK), and fly ash (FA) were used in binary (two-component) and ternary (three-component) cementititios blends. Within the frame work of this experimental study, a total of 16 SCMs were prepared having a constant water-binder (w/b) ratio of 0.40 and total cementitious materials content of 550 kg/m³. Then, the fresh properties of the mortars were tested for mini-slump flow diameter, mini-V-funnel flow time, setting time, and viscosity. Moreover, development in the compressive strength and ultrasonic pulse velocity (UPV) of the hardened mortars were determined at 1, 3, 7, 14, and 28 days. Test results have shown that using of FA and MK in the ternary blends improved the fresh properties and rheology of the mixtures when compared to those containing binary blends of FA or MK.     

Continuous precipitation in Cu-rich Cu-Ti binary and Cu-Ti-Al ternary alloys

An investigation has been carried out to study precipitation in a Cu-4% Ti binary and a Cu-2.1% Ti-2.4% Al ternary alloys which develop modulated microstructures upon ageing. Precipitate-free zones near the grain boundaries were observed on ageing immediately below a critical temperature representing the transition from the coherent to the incoherent region of the coherent phase diagram. In addition, a pronounced tendency for elastic interaction between the precipitate particles was detected, giving rise to aligned groups of precipitates containing a maximum of eight or nine particles in each group. At least near this critical temperature, decomposition occurs in the metastable region of the coherent phase diagram rather than in the spinodal region. The formation of the modulated structures in these alloys is, therefore, considered to arise not necessarily through spinodal decomposition. Continuous precipitation in a Cu-2.1% Ti-5% Al alloy is shown to result in spherical particles with no alignment. The effect of Al addition on the coherent solvus temperature is discussed in terms of a vacancy solute interaction mechanism.     

Solid self microemulsification of Atorvastatin using hydrophilic carriers: a design

Context: Atorvastatin has a limited advantage to formulate oral dosage forms.

Objective: To enhance the solubility of Atorvastatin and to design the suitable solid self-microemulsifying drug delivery systems (S-SMEDDS)

Materials and methods: The clear and transparent self-microemulsifying drug delivery system (SMEDDS) were formulated using coconut oil and isopropyl myristate as lipid phases; Tween 80 as surfactant; PEG 400 and glycerin as co-surfactant at 2:1, 3:1, 1:2 and 1:3 ratio. The pseudo ternary phase diagrams were constructed to identify the microemulsion region. The SMEDDS were evaluated for zeta potential, poly dispersity index, globule size, pH, viscosity and drug release. The solid SMEDDS were developed by employing adsorption and melt granulation methods. The S-SMEDDS were evaluated for micromeritics, morphology, solid state property, reconstitution ability, drug release and stability.

Results: The micro formulations formed with particle size of 25?nm had shown a 3-folds rise in drug release. The solid SMEDDS had reconstituted to a good microemulsion rapidly in 1–3?min, with a release of 94.62% at the end of 30?min and behaved as immediate releasing capsules. Their shelf-life was found to be 1.3 years.

Discussion: The 1:3 ratio SMEDDS had shown more drug release owing to their less particle size. The solid SMEDDS had shown an increased dissolution profiles than atorvastatin. The solid state of the drug had changed in formulation inferring their enhanced solubility.

Conclusion: The solid form of atorvastatin liquid SMEDDS had been formulated successfully with enhanced shelf life and solubility.     

Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

Context: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.

Objective: This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.

Method: DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).

Results and Discussion: Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93?±?11.01?µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9?±?0.2?µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization.

Conclusion: Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.     

Solubility enhancement of miconazole nitrate: binary and ternary mixture approach

Context: Enhancement of aqueous solubility of very slightly soluble Miconazole Nitrate (MN) is required to widen its application from topical formulation to oral/mucoadhesive formulations.

Objective: Aim of the present investigation was to enhance the aqueous solubility of MN using binary and ternary mixture approach.

Materials and methods: Binary mixtures such as solvent deposition, inclusion complexation and solid dispersion were adopted to enhance solubility using different polymers like lactose, beta-cyclodextrin (β-CD) and polyethylene-glycol 6000 (PEG 6000), respectively. Batches of binary mixtures with highest solubility enhancement potentials were further mixed to form ternary mixture by a simple kneading method. Drug polymer interaction and mixture morphology was studied using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively along with their saturation solubility studies and drug release.

Results: An excellent solubility enhancement, i.e. up to 72 folds and 316 folds of MN was seen by binary and ternary mixture, respectively. Up to 99.5% drug was released in 2?h from the mixtures of MN and polymers.

Discussion: Results revealed that solubility enhancement by binary mixtures is achieved due to surface modification and by increasing wettability of MN. Tremendous increase in solubility of MN by ternary mixture could possibly be due to blending of water soluble polymers, i.e. lactose and PEG 6000 with β-CD which was found to enhance the solubilizing nature of β-CD.

Conclusion: Owing to the excellent solubility enhancement potential of ternary mixtures in enhancing MN solubility from 110.4?μg/ml to 57?640.0?μg/ml, ternary mixture approach could prove to be promising in the development of oral/mucoadhesive formulations.     

In-situ investigation of the kesterite formation from binary and ternary sulphides

The formation of kesterite (Cu₂ZnSnS₄) from different stoichiometric mixtures of binary and ternary sulphides was investigated by in-situ high temperature synchrotron X-ray diffraction. The data were collected during the heating, the annealing and the cooling cycle. The Rietveld analysis of the diffractograms led us to determine temperature dependent phase changes qualitatively and quantitatively as well as the lattice constants of the different phases. Showing exemplarily with the mixture 2CuS + SnS + ZnS the formation of Cu₂ZnSnS₄ starts just below 300 °C. The volume size of the fcc anion substructure of the newly formed kesterite at 300 °C corresponds to the one of the ZnS phase. The lattice parameter of Cu₂ZnSnS₄ increases nonlinearly with increasing temperature showing possibly the trend of different formation stages. Comparing the lattice constants a and c of the several synthesized kesterites at 700 °C among each other and with a pre-synthesized kesterite, remarkable variations were obtained, whereas the ratio of the lattice parameter (c/2a) is comparable. These features led to the assumption that the cation distribution may vary in dependence on temperature and on the phase mixture used as starting material.     

Solid state and dissolution rate characterization of co-ground mixtures of nifedipine and hydrophilic carriers

Co-ground powders of the poorly water-soluble drug nifedipine and a hydrophilic carrier, [partially hydrolyzed gelatin (PHG), polyvinylpyrrolidone (PVP), sodium dodecyl sulfate (SDS), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), urea or Pluronic F108] were prepared in order to improve the dissolution rate of nifedipine. The effects of type of grinding equipment, grinding time, and type of hydrophilic carrier on the crystallinity of nifedipine (x-ray diffraction and differential scanning calorimetry) on the interaction between drug and carriers (differential scanning calorimetry), on the particle size and appearance (scanning electron microscopy), on the wettability (contact angle measurements), and on the drug release were investigated. Grinding nifedipine together with these carriers improved the dissolution rate. PHG-ground mixtures resulted in the fastest dissolution rate followed by PVP, SDS, HPMC, Pluronic, urea, and PEG. This effect was not only due to particle size reduction, which increased in the order PHG相似文献