Decrease In Dissolution Rate Research Articles

“Aging” in co-amorphous systems: Dissolution decrease and non-negligible dissolution increase during storage without recrystallization

Developing co-amorphous systems is a promising strategy to improve the water solubility of poorly water-soluble drugs. Most of the studies focused on the initial dissolution rate of the fresh co-amorphous systems, and only physical stability was investigated after storage. However, the maintenance of the enhanced dissolution rate of co-amorphous systems after storage is necessary for further product development. The maintenance of amorphous forms after storage does not always mean the maintenance of the dissolution rate. In this study, indomethacin, arginine, tryptophan, and phenylalanine were used as the model drug and the co-formers to prepare co-amorphous systems and then stored under dry condition and RH 60 ± 5 % condition. No recrystallization was observed after the storage for 40 d and 80 d. Interestingly, both intrinsic dissolution rate (IDR) decrease and unexpected increase after storage were confirmed. The further mixing of IND and the co-former at a molecular level and the moisture changes of the co-amorphous systems during storage were supposed to play important roles in the aging. This study reminds us that the possible dissolution changes (both dissolution decrease and increase) of co-amorphous systems during storage should be carefully considered, though these samples maintained amorphous forms.

Improved passivation performance of selective laser melted Inconel 718 alloy via tempering treatment

The passivation performance of the selective laser melted Inconel 718 alloy after tempering treatments was investigated, and the underlying mechanism for the improved passivation film protectiveness was explored. The dislocation reversion and the mitigated segregation of Nb, Mo and Ti at Laves and δ phases decreased the storage energy of lattice distortion were critical factors for the formation of more protective passivation film in chloride-containing solutions. The film formation rate increased after tempering, presenting the increased electric field strength and the decreased dissolution rate accordingly, as well as for the point defect diffusion coefficient and the oxygen vacancy flux therein.

Mechanisms controlling albite dissolution/precipitation kinetics as a function of chemical affinity: New insights from experiments in 29Si spiked solutions at 150 and 180 °C

Knowledge of the rates of dissolution of rock-forming minerals close to equilibrium and their dependence on ΔGr, the Gibbs free energy of reaction, is essential for describing the temporal and spatial evolution of many environmental and engineering processes involving solid/fluid interactions. In the present study we used the isotope-doping method to quantify albite forward and net dissolution rates. Batch experiments were performed at 150, 180 °C and pH = 9 at near equilibrium and equilibrium conditions (-25 ≤ ΔGr ≤ + 8.2 kJ/mol) in 29Si spiked solutions which were undersaturated with the secondary Al-Si solid phases likely to precipitate.The forward dissolution rates normalized to the initial BET surface area were found to decrease continuously and monotonically with increasing time and ΔGr, achieving values 1.3 to 2.4 orders of magnitude lower at chemical equilibrium than initial far from equilibrium values, with the highest rate decrease for the highest solid to fluid ratio. These rate drops were accompanied by an increase in BET specific surface areas associated with the formation of widespread dissolution features. A decrease of albite forward dissolution rate together with an increase of its BET surface area was also observed as a function of reaction time at far from equilibrium conditions (ΔGr ≤ − 65 kJ/mol). These observations are consistent with a continuous decrease with time and increasing ΔGr of albite effective surface area linked to the formation of unreactive negative crystal facets, in addition to etch pits stopping nucleating above a critical value of ΔGr. Thus, the observed decrease in albite dissolution rate as equilibrium is approached is not linked primarily to the increase in the contribution of the backward reaction but rather to the decrease of the forward reaction rate in conjunction with the decrease in the density of reactive sites at the mineral surface.The results of this study show that the characterization of the effective surface area and its evolution with reaction time and chemical affinity is crucial to deriving robust dissolution rates of well-crystallized minerals like feldspars. Dissolution experiments in 29Si spiked solutions of samples with different history and well-characterized effective surface area and surface morphology should help to better quantify the rate laws controlling silicate minerals weathering.

Microbial interactions with phosphorus containing glasses representative of vitrified radioactive waste

The presence of phosphorus in borosilicate glass (at 0.1 – 1.3 mol% P2O5) and in iron-phosphate glass (at 53 mol% P2O5) stimulated the growth and metabolic activity of anaerobic bacteria in model systems. Dissolution of these phosphorus containing glasses was either inhibited or accelerated by microbial metabolic activity, depending on the solution chemistry and the glass composition. The breakdown of organic carbon to volatile fatty acids increased glass dissolution. The interaction of microbially reduced Fe(II) with phosphorus-containing glass under anoxic conditions decreased dissolution rates, whereas the interaction of Fe(III) with phosphorus-containing glass under oxic conditions increased glass dissolution. Phosphorus addition to borosilicate glasses did not significantly affect the microbial species present, however, the diversity of the microbial community was enhanced on the surface of the iron phosphate glass. Results demonstrate the potential for microbes to influence the geochemistry of radioactive waste disposal environments with implication for wasteform durability.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Solid Dispersion of Acetosal Using Polyvinyl Pyrrolidone (PVP) K-30 in Tablets with Direct Compressing Method

Acetosal is classified in the Biopharmaceutical Classification System (BCS) class II (low solubility, high permeability). Low solubility causes a decreased dissolution rate. Polyvinyl pyrrolidone (PVP) K-30 is an inert carrier easily soluble in water and can influence the solubility of a drug substance. Efforts to increase the solubility of acetosal make a solid dispersion system. This study aims to determine the effect of the solid dispersion system of acetosal: PVP K-30 on dissolution rate, the ratio of the solid dispersion with the best dissolution rate, and the physical properties of acetosal tablets formed in the dispersion system. Solid dispersions using the dissolving method with variations in the concentration of acetosal: PVP K-30 1:1, 1:3, and 1:5. The results of the dissolution test of acetosal in solid dispersion powder, i.e., PVP Formula 1:5, which has the highest dissolution percentage compared to formula 1:1 and 1:3 with the concentration this formula was 140.96 mg, dissolution percentage was 28.19±0,63% in 30 minutes. Statistical results by ANOVA test show a significant difference of 0.044 (p<0.05). The physical properties of tablets with a dispersion system show higher addition of PVP K-30. This result is related to slower disintegration time and lower friability.

Optimising nasal powder drug delivery – Characterisation of the effect of excipients on drug absorption

The nasal physiology offers great potential for drug delivery but also poses specific challenges, among which the short residence time of applied drugs is one of the most striking. Formulating the drug as powder and using functional excipients are strategies to improve drug absorption. As nasal powders are still the minority on the market, there is a lack of data regarding their characterisation. This work aims at the characterisation of selected fillers (mannitol, microcrystalline cellulose) and mucoadhesives (pectin, chitosan glutamate, hydroxypropyl cellulose) with a set of methods that allows distinguishing their influences on dissolution and permeation of drugs, and on the viscoelasticity of the nasal fluid and thus the nasal residence time. Rheological studies revealed a potential of undissolved particles to prolong the residence time by increasing the elasticity of the nasal fluid. The assessment of drug dissolution showed a decreased dissolution rate in presence of insoluble or gelling excipients, which can be beneficial for drugs with low permeability, since embedded drugs are cleared slower than plain solutions. Drug permeation as important factor for the selection of excipients was evaluated with an RPMI 2650 cell model. Distinguishing the effects of excipients enables an effective selection of the most promising substances.

Analysing the impact of autocatalysis on the dissolution kinetics of uranium and plutonium mixed oxide powders by optical microscopy

Spent fuel dissolution is a key step in the recycling of nuclear fuel as it must ensure the production of a liquid solution consisted of concentrated nitric acid and the reusable fissile materials (uranium and plutonium), and decrease the fissile material hold-up in the system. This approach needs the understanding of chemical kinetic phenomena involved in the solid-liquid reaction. Optical microscopy was implemented to determine the dissolution rates of U-Pu-mixed oxides in nitric acid at different concentrations and temperatures for the first time. Mass transfer resistance was found negligible during dissolution indicating a process limited by the chemical reaction. Results showed a decrease in dissolution rate of the different oxides studied mainly due to the increment of plutonium content in the solids. Moreover, dissolution kinetics of solid U0.70Pu0.3O2 seems to improve when a catalyst is present in solution. Thus, the autocatalytic behaviour for the dissolution of spent fuel might occur for solids with 0% and up to 30%PuU+Pu of content.

Mechanism of surface corrosion resistance of 304 stainless steel processed by nanosecond laser pulses

AbstractA nanosecond pulsed fiber laser was used to modify the surface of 304 stainless steel. The compactness, microstructure, chemical composition, and corrosion resistance of the stainless steel passive film were observed by the blue dot detection method, scanning electron microscopy, x‐ray photoelectron spectroscopy, and electrochemical methods. The influence of different laser fluences on the stability and corrosion resistance of the stainless steel passive film was studied. The results show that with increasing laser fluence, the discoloration reaction time of the stainless steel surface increases first and then decreases, while the surface roughness decreases first and then increases. When the laser fluence is lower than 11.19 J/cm2, a compact and uniform passive film is formed. When the laser fluence is larger than this value, the stainless steel substrate is prone to secondary corrosion. Chromium oxides are enriched in the passive film, and the anodic dissolution rate decreases, which promotes a positive shift in the corrosion potential of the stainless steel, decreases the corrosion current density and increases the polarization resistance and the corrosion resistance. The surface corrosion resistance is thus significantly improved.

Surface area and size distribution of cement particles in hydrating paste as indicators for the conceptualization of a cement paste representative volume element

The conceptualization of a representative volume element (RVE) of hardened cement paste for numerical homogenization of mechanical problems rests on identifying the largest discernible microstructural feature, i.e. unreacted cement grains. While the particle size distribution (PSD) of anhydrous cement is a well-controlled production parameter, the size evolution of a representative cement grain throughout hydration remained unresolved. This study analyzes digitized 3D cement paste microstructures obtained from X-ray micro-computed tomography, coupled with CEMHYD3D hydration model, and segmented by image-processing tools, to obtain the full PSD and specific surface area evolutions of unreacted grains throughout hydration. Results provided indicate a representative grain size in the range of 30−40μm regardless of hydration elapsed, implying a cement paste RVE should amount to 150−200μm to realistically represent cement grains. The PSD shape remained self-similar and two distinctive hydration regimes were identified, differing in dissolution rate and specific surface area decrease, correlating with calcium sulfate reactivity peak. Both measures provide easily accessible microstructural features that may be used for constructing artificial RVEs of hardened cement paste in micromechanical models and related simulations, resting on experimental data.

Primary Production of Aluminium and Its Alloys in Molten Salts with Oxygen Evolving Anodes: Overview

Carbon dioxide and other greenhouse gases are emitted during the production of primary aluminium through the Hall-Heroult process. Moreover, the process requires specific energy consumption of as high as 14.685 kWh/tonne of Al. There is an urgency to replace the existing process with a more environmentally and economically friendly process. One such process involves the use of inert anodes instead of traditional carbon anodes, where Al2O3 → 2Al + 1.5O2 occurs instead of 1.5C + Al2O3 → 2Al + 1.5CO2. The life span of inert anodes can be improved by using them at low operating temperatures, however, alumina solubility and dissolution rate decrease at low operating temperatures. Instead of using a traditional NaF-AlF3 molten solution, NaF-KF-AlF3 or KF-AlF3 could be used as low-temperature electrolytes. Introducing KF salt into the NaF-AlF3 mixture increases the alumina solubility and reduces the liquidus temperature of the molten salt. Another factor that affects the liquidus temperature of the mixture and alumina solubility in the electrolyte is the cryolite ratio , where M = Na or K (or both). It should be noted that the cells with AlF3-rich NaF electrolytes suffer with problems such as high cell voltage, low aluminium purity and unstable frozen side ledges. The addition of CaF2, MgF or LiF to the electrolyte mixture could improve the physical-chemical properties of the electrolyte. For instance, the addition of CaF2 to KF-AlF3 molten salts improves the electrical conductivity of the electrolyte. Specific energy consumption of the cell can be significantly reduced by using a vertical electrode cell with reduced anode-cathode distance (ACD). However, the major problem with low ACD is the contamination of reduced aluminium at cathode by anode products. This problem can be solved by using suspension electrolytes where the electrolyte contains excess about of Al2O3 in the electrolyte which obstructs the transportation of anode products into the aluminium diffusion layer on the cathode, thus maintaining high aluminium purity. In this paper, we summarise the developments obtained in designing the inert anode cells. We mainly focus on three main components: Inert anodes, wettable cathodes, and low-temperature electrolytes. The influence of additives on the properties of electrolytes will be discussed in detail. We also discuss the energy consumption, environmental impact and economic aspects of producing aluminium using vertical electrode cells.

Electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions containing pH-dependent and poorly water-soluble rebamipide

In this study, the electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions (NSPs) containing poorly water-soluble drug was investigated. Anionic rebamipide (RBM) was chosen as a model drug because of its poor water solubility in low pH condition and ionizable acidic forms. Negatively charged sodium lauryl sulfate (SLS) and positively charged cetyltrimethylammonium bromide (CTAB) were selected as surfactants for the preparation of NSPs or in the dissolution medium. Salt-caged NSPs surrounded by NaCl were prepared by the HCl-NaOH neutralization method in the presence of poloxamer 407. Interestingly, the addition of positively charged CTAB in the preparation process or the dissolution media could interfere with the solubilization capacity of salt-caged NSPs containing a negatively charged drug via intermolecular electrostatic attraction. In the presence of positively charged CTAB, the salt-caged NSP was disordered in structure via electrostatic attractive interaction with partially ionizable anionic RBM resulting in changes in the physicochemical properties of the salt-caged NSP such as low drug content, increased particle size, decreased dissolution rate, and the formation of water-insoluble precipitates with rough and irregular crystals. This inhibitory effect of CTAB on the dissolution rate of pure RBM and the salt-caged NSP in pH 6.8 intestinal fluid was pronounced in a concentration-dependent manner mainly owing to the formation of precipitates, so-called poorly soluble complexes. When the salt-caged NSP (F1) was dissolved in DW containing CTAB, the dissolution rate decreased more significantly, dissolving less than 20% within 2 h. Depending on the surfactant charges, the charge density and the initial potential were varied during the dissolution of NSPs in deionized water (DW). In contrast, the negatively charged SLS did not significantly change the physicochemical properties of the salt-caged NSP. For example, the dissolution rate of the salt-caged NSP containing SLS in DW or pH 1.2 gastric fluid remained over 90% for 2 h. Surfactants for the formulation or dissolution media should be chosen carefully because of their effect on the physicochemical properties and solubilization capacity of salt-caged NSPs containing poorly water-soluble and ionizable drugs via electrostatic molecular interactions.

Mechanistic insight into gel-induced aggregation of amorphous curcumin during dissolution process

Amorphous curcumin (CUR) exhibited a decreased dissolution rate in comparison with the crystalline counterpart due to its gel formation during dissolution. The main purpose of the present study is to explore the mechanism of such gelation phenomenon. It was found that the dissolution of amorphous CUR and gel properties were influenced by the temperature and pH of the media. The formed gels were characterized by TPA, SEM, DSC, XRPD, FTIR and PLM. The results indicated that the gelation process led to the formation of a porous structure in which water molecules infiltrate, and entered into its supercooled liquid state with high viscosity when contacting aqueous media, accompanied by decreased Tg and crystalline transformation. In addition, mixing with hydrophilic excipients (such as hydrophilic silica) accelerated the gel formation of amorphous CUR, while the addition of hydrophobic excipients (such as hydrophobic silica and magnesium stearate) could effectively weaken and even eliminate the gelation, hence significantly improving its dissolution. Furthermore, according to contact angle measurement and fluorescence microscope observation, hydrophilic excipients were found to be able to accelerate water entering into the interior of amorphous CUR, hence facilitating the gelation, while hydrophobic excipients would hinder water infiltration into the powder and thus achieve degelation. In conclusion, it is important to recognize that the gelation potential of some amorphous materials should be considered in developing robust amorphous drug product of high quality and performance.

Stability Testing of Amoxicillin Nano-suspension as Promising Tool for Drug Delivery System

While nano-suspension amoxicillin is one of the approaches for improving dissolution rate of amoxicillinan antibiotic used widely. Stabilizing these nanodosage forms is always a challenge. The present study utilizes nanoprecipitation solvent evaporation technique for preparation of amoxicillin nanoparticles andproposed stability study approach of the same. The methodology was based on investigating stability of amoxicillin nano suspension in vitro, the optimized drug(polymer ratio re-formulated into nano-suspensions) and we compared our results with marketed suspensions. Samples were initially characterized and then subjected to stability testing at ambient temperature and relative humidity up to 6 months assayed using a validated HPLC method. During initial characterization, increase in saturation solubility and dissolution rate observed in all samples. During stability testing, there was gradual decrease in saturation solubility and dissolution rate of the samples, over the period of 3 months. This study considers long-term isothermal measurements, consistent with short-term non-isothermal (accelerating) measurements, providing predictive model to calculate the isothermal degradation periods. As per our results, we agree with the possibility to calculate the value of kinetic constants based on a fixed degradation limit, regardless of the shape of the curve. The accuracy of the prediction would be assessed by comparison of estimated shelf life versus data coming from traditional stability studies.

Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process.

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 μm) compared to that of unprocessed fenofibrate (approximately 20 μm) and SD-processed particles (approximately 40 μm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

Effect of transitional aluminas on Portland cement hydration, phase assemblage and the correlation to ASR preventing effectiveness

This study reveals the impact of transitional aluminas on the hydration kinetics, phase assemblage of Portland cement, and ASR preventing effectiveness. Transitional aluminas were obtained by annealing reactive alumina mainly consisting of γ-Al2O3 at various temperatures. Their impacts on hydration kinetics at early age and phase assemblage were examined on a Portland cement blended with 7 wt% transitional aluminas. The increase in annealing temperature reduces the reactivity of transitional aluminas, manifesting into a decreasing dissolution rate in stimulated pore solution. The rapid dissolution of transitional aluminas annealed below 600 °C prolonged the induction period and inhibited the dissolution of C3S. Their continuous dissolution contributes to the formation of monosulfate, (SO4-OH) AFm, and katoite. As a result, the incorporation of these transitional aluminas prevents ASR effectively. In contrast, transitional aluminas annealed above 600 °C present as fillers due to their decreased reactivity, hence promoting the hydration process and exerting little effect on phase assemblage.

Surface evolution of aluminosilicate glass fibers during dissolution: Influence of pH, solid-to-solution ratio and organic treatment

Materials made of synthetic vitreous mineral fibers, such as stone wool, are widely used in construction, in functional composites and as thermal and acoustic insulation. Chemical stability is an important parameter in assessing long term durability of the products. Stability is determined by fiber resistivity to dissolution, where the controlling parameters are solid surface area to solution volume ratio (S/V), pH and composition of the fibers and organic compounds used as binders. We investigated stone wool dissolution under flow through conditions, far from equilibrium, at pH range of 2 to 13, as well as under batch conditions, close to equilibrium, for up to 28 days, where S/V ranged from 100 to 10000 m−1. The dissolution rate of stone wool shows minimum at pH 8.5 and increases significantly at pH < 4.5 and pH > 12. In close to equilibrium conditions, S/V defines the steady state concentration for the leached components. Decreased dissolution rate could result from evolution of a surface leached layer or the formation of secondary surface phases or both. We suggested three dissolution rate controlling mechanisms, which depend on pH. That is, dissolution is controlled by: a SiO2 rich surface layer at pH < 4.5; by adsorption of an Al and Al-Si mixed surface layer at 5 < pH < 11 and by divalent cation adsorption and formation of secondary phases (silicates, hydroxides) at pH ∼ 13. The organic compounds, used to treat the stone wool fibers during manufacture, had no influence on their dissolution properties.

Supercritical Fluid Technology for the Development of 3D Printed Controlled Drug Release Dosage Forms.

Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from polylactic acid (PLA) using a fused deposition modelling (FDM) 3D printer. The 3D printed drug carriers were then loaded with Ibuprofen as a model drug, employing the controlled particle deposition (CPD) process from supercritical CO2. Carriers with varying pore sizes (0.027–0.125 mm) were constructed and loaded with Ibuprofen to yield drug-loaded carriers with a total amount of 0.83–2.67 mg API (0.32–1.41% w/w). Dissolution studies of the carriers show a significantly decreasing dissolution rate with decreasing pore sizes with a mean dissolution time (MDT) of 8.7 min for the largest pore size and 128.2 min for the smallest pore size. The API dissolution mechanism from the carriers was determined to be Fickian diffusion from the non-soluble, non-swelling carriers. Using 3D printing in combination with the CPD process, we were able to develop dosage forms with individually tailored controlled drug release. The dissolution rate of our dosage forms can be easily adjusted to the individual needs by modifying the pore sizes of the 3D printed carriers.

Studying effect of glyceryl palmitostearate amount, manufacturing method and stability on polymorphic transformation and dissolution of rifaximin tablets.

Rifaximin (RFX) exhibit polymorphism and commercial formulation contains the α form. The polymorphic transformation of the RFX in the drug product have significant effect on the clinical outcome. The focus of present work was to understand effect of formulation component and manufacturing method, and exposure to stability condition on polymorphic stability and dissolution of RFX tablets. The RFX tablets containing 2.5, 5 and 10% glyceryl palmitostearate (GPS) were manufactured by direct-compression and wet-granulation followed by compression. Ethanol was used as a granulating solvent. The tablets were packed in pharmacy vials and exposed to 40°C/75% RH for four weeks. The tablets were characterized for polymorphic form by X-ray powder diffraction (XRPD) and Fourier infrared spectroscopy (FTIR), assay and dissolution. Before exposure to stability condition, dissolution ranged from 78.0±2.3 to 81.9±3.5%, and 72.7±2.0 and 75.9±5.8% in directly compressed and ethanol-granulated formulations, respectively. GPS amount of 10% caused a decrease in dissolution albeit insignificant (p>0.05). The polymorphic forms of RFX were α and γ in directly compressed and ethanol-granulated formulations, respectively. There was a decrease in dissolution rate and extent after exposure to 40°C/75% RH in directly compressed formulations. On the other hand, only dissolution rate was affected in ethanol-granulated formulations. The dissolution ranged from 52.8±2.0 to 70.0±3.0% in directly compressed formulations after four weeks exposure to 40°C/75% RH exposure. A decrease in dissolution was linked to polymorphic transformation of the drug and GPS in the formulations after exposure to stability condition. XRPD and FTIR data indicated α to β transformation in directly compressed formulations while no polymorphic change was observed in ethanol-granulated formulations. In conclusion, this study clearly showed effect of formulation and manufacturing variables, and stability exposure on the polymorphic stability and dissolution of RFX, which may have clinical ramification.

Preparation, characterization and improved release profile of ibuprofen-phospholipid association

Ibuprofen is a widely prescribed non-steroidal and anti-inflammatory drug, which is practically insoluble in water and causes gastrointestinal (GI) side effects. Ibuprofen-phosphathidylcholine association (IPA) was prepared by refluxing ibuprofen and phosphathidylcholine in three different molar ratios (1:0.25, 1:0.5 and 1:1) in aim to induce the amorphous nature of ibuprofen and increase its solubility. The characteristics of IPA were evaluated by H1-NMR, FT-IR spectra, X ray diffraction (XRD), differential scanning calorimetry (DSC), drug content, photon correlation spectroscopy, computational molecular simulation, solubility and in vitro dissolution study. Computational molecular simulation, DSC, FT-IR, H1-NMR and XRD patterns confirmed the reaction between carboxyl group of ibuprofen and polar moiety of phosphathidylcholine. IPAs showed an increase in solubility in phosphate buffer medium (pH 7.2) and a decrease in solubility in HCl medium (pH 1.2). The IPA dissolution rate increased in the simulated intestinal medium, whereas the dissolution rate of the IPA decreased in the simulated gastric medium. It is concluded that the phosphatidylcholine association of ibuprofen may be of potential use for improving the ibuprofen solubility and hence its bioavailability. Furthermore, considering decrease of dissolution rate of IPA in acidic medium, it may also reduce GI toxicity of ibuprofen. Moreover, comparing different molar ratios of IPA, there is no significant difference in their characteristics and dissolution profiles.