Measured Dissolution Rates Research Articles

Chemical durability of vitrified wasteforms: effects of pH and solution composition

AbstractVitrification is used for the immobilization and conditioning of high-level waste (HLW) arising from the reprocessing of spent nuclear fuel in the UK. Vitrification is also under consideration for the immobilization of certain intermediate-level wastes (ILW), where there may be advantages of volume reduction and removal of uncertainties in long-term waste behaviour, compared to encapsulation in a cement grout. This paper gives an overview of recent work into the chemical durability of UK vitrified wasteforms to inform the technical specification for the disposal facilities for these waste products and the treatment of their long-term behaviour in post-closure performance assessment. This has included: (1) measurements of the initial glass dissolution rates of a simulated HLW Magnox waste glass in a range of groundwater types representative of potential UK host geologies and in simulated high pH near-field porewaters relevant to potential disposal concepts, using Product Consistency Test type-B (PCT-B) at 40°C; and (2) durability testing of three simulant ILW glasses in a saturated calcium hydroxide buffered solution to simulate conditions in cement-based disposal vaults, using PCT-B tests at 50°C.The experimentally defined initial rate of HLW Magnox waste glass dissolution in a range of simulated groundwater compositions appears to be similar regardless of the ionic strength and major element composition of the solution. The release of caesium from HLW Magnox waste glass appears to be sensitive to solution composition. Caesium is selectively retained in the glass compared to other soluble components in the two low ionic strength solutions, but is released at similar rates to other soluble components in the three groundwaters and Ca(OH)2 solution. Whether this change in caesium retention is an ionic strength effect or is related to changes in the nature of the surface alteration layer formed on the glass, has yet to be established. For HLW Magnox waste glass, dissolution is accelerated at high pH in NaOH solution, however, the presence of calcium acts to mitigate the effects of high pH, at least initially. In Ca(OH)2 solution, calcium is found to react with all the glasses studied leading to the formation of calcium-containing alteration products. The initial dissolution behaviour in Ca(OH)2 solution varies with glass composition and in particular appears to be sensitive to the boron content.

A new approach for measuring dissolution rates of silicate minerals by using silicon isotopes

The two major problems in measuring dissolution rates under close-to-natural conditions in laboratory experiments are: (1) our inability to measure small differences in concentration between solutions with relatively high concentrations and (2) the inherent problem that the change in solution concentration is affected by both the dissolution of the primary mineral and the precipitation of secondary minerals. The present manuscript proposes and tests a novel method, “the isotope ratio method”, for measuring slow dissolution rates of silicate minerals by measuring the change in the ratios between stable isotopes of silicon of a spiked solution.Based on mass balance calculations, two equations that describe the dissolution rate of a silicate mineral in a batch reactor and in a flow-through reactor at steady-state are developed. The precipitation rate of the secondary mineral may be calculated by subtracting the release rate of Si that was calculated using isotope dilution from the rate that was calculated using the proposed isotope ratio method.Numerical simulations of flow-through and batch experiments demonstrate that the “isotope ratio method” is significantly more precise than conventional methods. The analytical uncertainty for the determination of dissolution rates was found to be low for the entire range of reported field-based dissolution rates. The calculation showed that even relatively large isotopic fractionations (up to ε values of 20‰), introduce insignificant uncertainties.Preliminary flow-through experiments support the above conclusion that dissolution rate may be obtained accurately and with small uncertainty using the proposed “isotope ratio method”.

Experimental determination of rhyolitic glass dissolution rates at 40–200 °C and 2 < pH < 10.1

The steady-state dissolution rates of Öraefajökull rhyolitic glass were measured in titanium mixed-flow reactors as a function of aqueous Al, Si, and oxalic acid concentration at temperatures from 40 to 200°C and pH from 2 to 10.1. Measured dissolution rates at were found to be consistent withr+=Ae-EARTaH+3aAl3+1/nwhere r+ refers to the specific dissolution rate, A represents a pre-exponential factor equal to 1.4×10−5mol/cm2/s, EA denotes an activation energy equal to 55.15kJ/mol, n represents a stoichiometric factor equal to 11.1, R designates the gas constant, T corresponds to the absolute temperature and ai defines the activity of the subscripted aqueous species. In accord with this equation, aqueous organic ligands will enhance rates by complexing with aqueous Al3+, thus lowering aAl3+. The observed variation of rhyolite dissolution rates with solution chemistry and temperature is similar to that previously observed for basaltic glass. This similarity suggests that all natural Al-silicate volcanic glasses have similar dissolution mechanisms consisting of the sequential removal of metals from the glass structure via proton exchange reactions. The overall dissolution rate within this mechanism is controlled by the detachment of Si tetrahedral that have been partially liberated from the glass structure through the removal of adjoining Al.

Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug.

In vitro dissolution of uranyl acetate using different methods

The dissolution rate of a material in the lung is an important parameter in evaluating the risk to humans following accidental inhalation of a substance and is also a parameter that may be useful in characterizing particles for nuclear forensics analysis. Conventional methods of measuring dissolution rates in vitro involve exposing the material or particles to a solvent, such as water, saline, or solutions that simulate lung fluid, and measuring the fraction of material that dissolves with time. A new device for measuring dissolution rates for small samples, especially individual particles, was evaluated that incorporates a regenerated cellulose dialysis membrane fixed to the bottom of a small, 2 mL plastic cup that fits into the top of a 50 mL plastic centrifuge tube. The cup is easily transferred among a series of tubes containing solvent to measure rate of dissolution. The dialysis membrane has a diffusion rating of 20 kDa molecular weight cut off which greatly exceeds the size of the dissolved uranium molecule. The performance of the dialysis cup device was evaluated by measuring the dissolution rate of uranyl acetate in distilled water, phosphate buffered saline (PBS), and simulated lung fluid (SLF). These results were compared to the dissolution rate measured using the traditional filter sandwich method in which a sample is sealed between two hydrophilic membranes. Although the majority of uranyl acetate dissolved in SLF within 30 min using the filter sandwich method, most of the uranyl acetate was undissolved in PBS and SLF using the dialysis membrane device. Reactions between the dissolved uranyl acetate, solvent, and the dialysis membrane likely caused the membrane to swell, shrinking the pore size, and thus reducing the transport of dissolved uranium across the membrane. Use of the dialysis cup device for evaluating dissolution rates for uranium-bearing materials in solvents containing a high concentration of salts is therefore not recommended.

Dissolution measurement free from mass transport

Standard dissolution experiments are carried out in stirred liquid. Therefore, the measured dissolution rate contains also diffusive and convective contributions, besides the desired surface reaction contribution. We present here a methodology, based on the hydrodynamical analysis of classical dissolution experiments, enabling us to extract the pure dissolution rate constant from the set of the already measured dissolution rates. The application of this analysis to the case of gypsum shows that the removal of the mass transport contribution from the dissolution rates of this mineral found in the literature brings, despite their apparent inconsistency, a coherent description of its dissolution kinetics and a well-defined value of its rate constant.

Locally Enhanced Dissolution Rate as a Probe for Nanocontact-Induced Densification in Oxide Glasses

Atomic force microscopy (AFM) was used to characterize the surface damage (nanoindentations) effect on the chemical durability of glass surfaces (silica and soda-lime silicate glasses, WG). In basic solutions, an enhanced dissolution rate is reported and quantified at indentation sites (+10.5 nm/h and +52 nm/h for silica and WG, respectively) whereas none was observed once the indented surfaces were thermally annealed at 0.9 × T(g) for 2 h, a thermal treatment known for curing high pressure-induced permanent densification in oxides glasses. A direct link between high pressure-induced structural modifications encountered during nanoindentation and the measured dissolution rates is established. It is shown that this property conjointly used with the high resolution of the atomic force microscope may be used for probing, at the nanometer scale, the size and the nature of the structurally modified area underneath residual nanoindentation impressions. As an example, for 10 mN Vickers nanoindentations on WG, the zone affected by the permanently and structurally modified zone under the residual impression is found to be equal to (741 ± 30) nm with a transition zone thickness from the fully densified material to the elastically deformed one ranging between 115 and 165 nm.

Crystallization and Polymorphism of Felodipine

Two previously known polymorphs (forms I and II) and two new polymorphs (forms III and IV) of the calcium-channel blocker felodipine were obtained during attempts to cocrystallize the compound with a variety of potential cocrystal formers. A correlation was observed between the polymorphic outcome and the effective pH value in the presence of the cocrystal former, and it was possible subsequently to produce the four polymorphs by pH adjustment using H2SO4(aq) or NaOH(aq). This suggests that there is no distinct “structure-directing” role for the molecular additives present during the cocrystallization trials. The crystal structures of the new forms III and IV were determined using single-crystal X-ray diffraction. Forms I, II, and III were obtained in bulk form and characterized by a variety of analytical methods, including thermal analysis, solution calorimetry, intrinsic dissolution rate measurement, and solubility measurement. Form IV could be obtained only as a few isolated single crystals, and its cr...

Steady-state dissolution kinetics of mineral ferric phosphate in the presence of desferrioxamine-B and oxalate ligands at pH = 4–6 and T = 24 ± 0.6 °C

Ferric phosphate (FePO4·2H2O) is one of the most common secondary phosphate minerals in the environment. Nevertheless, few studies address the biological dissolution mechanism(s) of FePO4·2H2O. This paper reports steady-state dissolution rates of synthetic FePO4·2H2O at 4≤pH0≤6 by desferrioxamine-B (DFO-B) and oxalate (Ox) ligands. The composition of the influent solution was 10mM NaClO4, 5mM MES buffer. The influent solution was adjusted to 4≤pH0≤6 by adding aliquots of HNO3 or NaOH stock solution. The initial concentrations of DFO-B and Ox, [DFO-B]0 and [Ox]0, ranged from 0 to 135μM, and 0 to 345μM. Geochemical thermodynamic equilibrium modeling was conducted using MINEQL+ (Schecher and McAvoy, 1998). Speciation calculations were based on thermodynamic formation constants at 298.17K, K298 (infinite dilution reference state). Ligand-promoted dissolution rates were determined after steady-state values. Iron concentrations in the effluent solution were quantified (t>500h). Typical effluent-flow rate was maintained at 0.10±0.01mLmin−1. The measured dissolution rate of FePO4·2H2O by DFO-B and Ox, RDFO–OxObs, was compared to the sum of dissolution rates by DFO-B (RDFO-B) or Ox (ROx), RDFO–OxSum (RDFO–OxSum=RDFO‐B+ROx). Results were analyzed using the t student test. Obtained data values with p≤0.05 (⁎) and ≤0.01 (⁎⁎) were considered to differ statistically from control experiments. Dissolution rates by DFO-B (RDFO-B) increased with [DFOB]0, and no evidence of surface masking became apparent. By contrast, dissolution rates by Ox (ROx) varied with [Ox]0 and pH0. The kinetics of dissolution by Ox was not explained by a first-order mineral dissolution behavior. Dissolution rates by DFO-B and Ox (RDFO–OxObs) surpassed RDFO-B or ROx, and increased with proton activity. Reacting FePO4·2H2O with DFO-B and high amounts of Ox resulted in higher values for RDFO–OxObs relative to RDFO-B. Observed (RDFO–OxObs) to calculated (RDFO–OxSum=RDFO‐B+ROx) ratio was found to be highest at [DFOB]0=50μM and [Ox]0=49μM. Increases in the proton activity favors the dissolution of FePO4·2H2O by DFO-B and Ox, explained because the sequestration of Fe(III) at the surface vicinity in the form of adsorbed Fe(III)-oxalate complexes. A direct comparison between the dissolution behavior of FePO4·2H2O by DFO-B and Ox against those for goethite (α-FeOOH) and Al goethite (AlFeOOH) was conducted. The dissolution behavior was found to be a function of the mineral structure. RDFO-B values for FePO4·2H2O by 22.5μM DFO-B surpassed those for α-FeOOH or α-AlFeOOH by 20μM DFO-B, namely, 37, and 11.6 and 3–5μmolkg−1h−1, respectively. ROx values for FePO4·2H2O by 49mM Ox surpassed that for α-FeOOH by 70μM Ox or α-AlFeOOH by 50μM Ox, namely, i.e., 12, and 0.7 and 0.1μmolkg−1h−1. The latter results agree with the idea of the inhibition of Fe release in goethite because its sequestration in the form of adsorbed Fe(III) oxalate complexes. In contrast, a different scenario holds true for dissolution by 50μM DFO-B and 49μM Ox. The dissolution rates for FePO4·2H2O, α-FeOOH, and α-AlFeOOH correspond to 50, and 39–42 and 71–129μmolkg−1h−1, respectively. The high extent of iron release from Al goethite is best explained because high-energy surface sites formed after Al substitution in goethite.

Measurement of oxide thin film dissolution rate on the HA‐coated Ti alloy by scanning electron microscopy and impedance spectroscopy

The measurement of oxide thin film dissolution rate on the hydroxyapatite (HA)‐coated Ti alloy was researched by scanning electron microscopy and impedance spectroscopy. For this study, Ti‐35Nb‐xHf alloys containing Hf from 3 wt.% to 15 wt.% were manufactured by using a vacuum furnace system. Ti‐35Nb‐xHf alloys were homogenized for 24 h at 1000 °C. HA thin films for applications in the bio‐medical field were grown by radio‐frequency (RF) magnetron sputtering techniques. RF power of 50 W was applied to the target for 1 h at 100 °C. The microstructure, phase, and composition of HA‐coated Ti‐35Nb‐xHf alloys were examined by field‐emission scanning electron microscopy, energy dispersive X‐ray spectroscopy, and X‐ray diffraction. The estimation of corrosion behavior was performed by potentiodynamic and alternating current impedance test. The experimental results indicated that the as‐sputtered coating had quite uniform thickness and well bonded to the substrate. The HA film on the Ti‐35Nb‐xHf alloys exhibited a better electrochemical behavior than bared Ti‐35Nb‐xHf alloys in the passive region. The high capacity behavior (constant phase element) was observed for HA‐coated Ti‐35Nb‐15Hf alloy, and the polarization resistance (Rp) of HA‐coated Ti‐35Nb‐xHf alloys was higher than that of uncoated Ti‐35Nb‐xHf alloys. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Effects of Charcoal Carbon Crystallinity and Ash Content on Carbon Dissolution in Molten Iron and Carburization Reaction in Iron-Charcoal Composite

Charcoal use instead of fossil fuel is one of the possible technologies for mitigation of CO2 emission in the steel industry because charcoal can be considered as “carbon-neutral” material. In this study, the possibility of utilization of charcoal as carbon source for carburization reaction was examined; more specifically effects of carbon crystalinity and ash in charcoal on carbon dissolution into molten iron and iron carburization reaction in iron-charcoal composite were investigated. Two kinds of experiments were carried out. One is measurement of charcoal carbon dissolution rate in iron bath. Another is observation of isothermal reaction between iron and charcoal in a composite sample. Several kinds of charcoal with relatively low ash content were applied as experimental samples. Charcoal samples were treated with several heating patterns to control their carbon crystallinity. Additionally, charcoal samples were treated with acid solutions, HCl and HF, to control the ash content in them. From these investigations, following results were revealed. Charcoal heat-treated at low temperature, 1 273 K, has advantage for carbon dissolution reaction into iron bath. Charcoal ash strongly prevents the carburization reaction between iron and carbon in the composite sample.

Formulation of cefuroxime axetil oral suspension and investigation of its pharmaceutical properties.

Cefuroxime is the second generation cephalosporin, which its intravenous and oral dosage forms are available. Oral route is the selective method for administration of most of the drugs. The aim of this study was formulating 'for oral' cefuroxime axetil suspensions. Minitab (ver.15) was used to design the formulations containing 125 mg of cefuroxime in 5 ml vehicle. After selecting the acceptable preparations, physical stability tests and other tests such as dissolution rate, pH, zeta potential and viscosity measurement of formulations were performed. From all 33 formulations, only 9 were selected to further investigation. Considering no sedimentation, the sedimentation volume was determined to be 1. The degrees of flocculation were also equal to 1. All selected formulations released the drug between 81-100% in 30 minutes which was acceptable according to the USP32 criteria. The results of assay test also proved that all formulations contain the drug in acceptable range (91-106%). The viscosity curves showed that the systems were pseudo plastic and thixotrop. Designed cefuroxime axetil formulations had good qualities and could be added as a new product to Iran drug marketing.

Oyster Shell Dissolution Rates in Estuarine Waters: Effects of pH and Shell Legacy

ABSTRACT Oyster shell is a crucial component of healthy oyster reefs. Shell planting has been a main component of oyster restoration efforts in many habitats and has been carried out on scales from individual and grassroots efforts to multiagency efforts across entire estuaries. However, the cycling and lifetime of the shell that makes up the bulk of an oyster reef has only recently received attention, and most of the work to date has focused on the role of epi- and endobionts on shell degradation. Here we report findings from a laboratory study in which we manipulated pH in a flow-through control system using water from the mesohaline mouth of the Patuxent River to measure dissolution rates of intact oyster shell. Shells from the Eastern oyster (Crassostrea virginica Gmelin 1791) with three different legacies were exposed to 4 levels of pH that encompass a range typical of the mesohaline waters of the Chesapeake Bay (∼7.2–7.9 on the NBS scale). Mass loss over a 2-wk period was used to measure dissolution...

Ionic Co-crystals of Organic Molecules with Metal Halides: A New Prospect in the Solid Formulation of Active Pharmaceutical Ingredients

Ionic co-crystals (ICCs) are constituted of inorganic salts and organic molecules. These crystals combine ionic interactions with classical supramolecular bonding such as hydrogen and dipole-bonding interactions. Such is the case of the hydrogen bonds between N–H and C═O dipoles in primary and secondary amides when these cocrystallize with an ionic material such as CaCl2. Here, we report our results of the preparation and characterization of a series of ICCs in which the molecular component is an active pharmaceutical ingredient (API) or a precursor of APIs, namely, barbituric acid, diacetamide, malonamide, nicotinamide, and piracetam, while the inorganic salt coformer is CaCl2. CaCl2 has been chosen, inter alia, for its nontoxicity and potential applications in the pharmaceutical field. Preparative methods include conventional crystallizations from solution, as well as slurry and solid state techniques (grinding and kneading). All crystal structures reported herein were determined either from single crystal diffraction data or from powder diffraction data, using simulated annealing procedures. Crystalline products were analyzed by differential scanning calorimetry, thermogravimetric analysis, and variable temperature X-ray powder diffraction. Intrinsic dissolution rate measurements were also performed on nicotinamide and piracetam ICCs.

In situ atomic force microscopy measurements of biotite basal plane reactivity in the presence of oxalic acid

We have used a direct imaging technique, in situ atomic force microscopy (AFM), to observe the dissolution of the basal biotite surface by oxalic acid over a range of temperatures close to ambient conditions, using a specially designed AFM liquid cell and non-invasive intermittent contact mode of operation. From the 3-dimensional nanometre-resolution data sets, we observe a process characterised by the slow formation of shallow etch pits in the (0 0 1) surface and fast growth of etch pits from the resulting steps, which represent proxies for the {h k 0} surface. Measurements of dissolution rates as a function of temperature allow a determination of an apparent activation energy ( E a,app ) for the process, via mass-loss calculations from image analysis. We obtain a value of E a,app = 49 ± 2 kJ mol −1, which is consistent with separate calculations based on planar area etch pit growth, and measurements of etch pit perimeters, indicating that this value of E a,app is representative of {h k 0} surface dissolution. The measurement of etch pit perimeters also enables an estimation of apparent activation energy as a function of step density indicating substantially higher apparent activation energy, up to E a,app = 140 kJ mol −1, on extrapolation towards a pristine surface with no defects. We suggest that this higher value of E a,app represents the slow formation of etch pits into the (0 0 1) surface.

P.1.c.005 Protective effect of Platycodon grandiflorum in a middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats

The effect of malonate on the dissolution rate of the reservoir minerals: albite, quartz, and microcline has been examined. The effect of pH on rate has been decoupled from the effect of the ligand by controlling pH using dilute buffer solutions at values of pH 4 through pH 10 at 70°C. Any effect of the buffer ligands (acetate and borate) or alkali cation (Na) on rate was accounted for by comparing the measured dissolution rates in buffer solutions with and without malonate. Flowing reactors were used and malonate concentration was varied from 1 to 100 mmolal.As malonate anion concentration is increased, the dissolution rate of these minerals also increases. At moderately acidic to near neutral pH in the solutions containing the highest malonate concentration, malonate most significantly increases the dissolution rate of the silicates over that expected due to simple hydrolysis. At alkaline pH the effect of malonate on the dissolution rate of these silicates is not significant, compared to the dissolution rate due to simple hydrolysis alone.

Measuring silver nanoparticle dissolution in complex biological and environmental matrices using UV–visible absorbance

Distinguishing the toxic effects of nanoparticles (NPs) themselves from the well-studied toxic effects of their ions is a critical but challenging measurement for nanotoxicity studies and regulation. This measurement is especially difficult for silver NPs (AgNPs) because in many relevant biological and environmental solutions, dissolved silver forms AgCl NPs or microparticles. Simulations predict that solid AgCl particles form at silver concentrations greater than 0.18 and 0.58 μg/mL in cell culture media and moderately hard reconstituted water (MHRW), respectively. The AgCl NPs are usually not easily separable from AgNPs. Therefore, common existing total silver techniques applied to measure AgNP dissolution, such as inductively coupled plasma mass spectrometry (ICP-MS) or atomic absorption, cannot accurately measure the amount of silver remaining in AgNP form, as they cannot distinguish Ag oxidation states. In this work, we introduce a simple localized surface plasmon resonance (LSPR) UV-visible absorbance measurement as a technique to measure the amount of silver remaining in AgNP form for AgNPs with constant agglomeration states. Unlike other existing methods, this absorbance method can be used to measure the amount of silver remaining in AgNP form even in biological and environmental solutions containing chloride because AgCl NPs do not have an associated LSPR absorbance. In addition, no separation step is required to measure the dissolution of the AgNPs. After using ICP-MS to show that the area under the absorbance curve is an accurate measure of silver in AgNP state for unagglomerating AgNPs in non-chloride-containing media, the absorbance is used to measure dissolution rates of AgNPs with different polymer coatings in biological and environmental solutions. We find that the dissolution rate decreases at high AgNP concentrations, 5 kDa polyethylene glycol thiol coatings increase the dissolution rate, and the rate is much higher in cell culture media than in MHRW.

Micronisation of carbamazepine through rapid expansion of supercritical solution (RESS)

A large number of pharmaceutical compounds are orally administered to the human body. If the drug shows a poor water-solubility and therewith low dissolution rate, a high dosage is needed which may cause undesired side effects to the human body. To improve the dissolution properties of these poorly water-soluble drugs, a large number of various strategies including micronisation, nano-emulsions and polymeric micelles are applied. In this paper we report on the formation of submicron carbamazepine particles by rapid expansion of supercritical solutions (RESS). The unprocessed and processed carbamazepine powder was characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate measurements. Due to the existence of four different polymorphic forms of carbamazepine, one focus is on the modification or change of the crystal structure of carbamazepine caused by RESS. The experimental results show that the particle size can be reduced at least by a factor of 29 to median sizes between 0.43 and 0.9μm and that pure C-monoclinic carbamazepine particles can be produced for pre-expansion temperatures ≥363K. The dissolution rate of the product at pH 2 and 310K could be enhanced in comparison to the unprocessed material.

Micronisation of carbamazepine through rapid expansion of supercritical solution (RESS)

Abstract A large number of pharmaceutical compounds are orally administered to the human body. If the drug shows a poor water-solubility and therewith low dissolution rate, a high dosage is needed which may cause undesired side effects to the human body. To improve the dissolution properties of these poorly water-soluble drugs, a large number of various strategies including micronisation, nano-emulsions and polymeric micelles are applied. In this paper we report on the formation of submicron carbamazepine particles by rapid expansion of supercritical solutions (RESS). The unprocessed and processed carbamazepine powder was characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate measurements. Due to the existence of four different polymorphic forms of carbamazepine, one focus is on the modification or change of the crystal structure of carbamazepine caused by RESS. The experimental results show that the particle size can be reduced at least by a factor of 29 to median sizes between 0.43 and 0.9 μm and that pure C-monoclinic carbamazepine particles can be produced for pre-expansion temperatures ≥363 K. The dissolution rate of the product at pH 2 and 310 K could be enhanced in comparison to the unprocessed material.

The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions.

Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.