Faster Dissolution Rate Research Articles

Sonication-Assisted Self-Assembled Resveratrol Nanoparticles with Enhanced Antiviral and Anti-inflammatory Activity against Respiratory Syncytial Virus-Induced Pneumonia.

Respiratory syncytial virus (RSV)-induced viral pneumonia in children is common worldwide. Its high occurrence and lack of an effective vaccine make it a leading cause of death in children. Severe RSV infection can trigger uncontrolled inflammatory responses in patients, so the development of small molecule drugs with the dual function of "direct antivirus" and "inflammatory response regulation" is welcome. Resveratrol (Res) has been reported to have antiviral and anti-inflammatory pharmacological effects, but its application is limited because of its poor water solubility and oral bioavailability. Based on small-molecule nanotechnology, we developed a sonication-assisted self-assembly method for preparing insoluble Res into highly soluble resveratrol nanoparticles (Res NPs). The obtained Res NPs exhibited a higher water solubility and a faster dissolution rate, which was more conducive to the effectiveness of Res in addressing RSV-induced viral pneumonia. In vitro studies had shown that Res NPs played an antiviral role by inhibiting RSV replication and reducing the production of pro-inflammatory cytokines. Nebulized inhalation administration of Res NPs prolonged the drug's residence time in the lungs, which appears to increase the accumulation and effectiveness of Res NPs. Additionally, in vivo studies had demonstrated significant benefits of Res NPs in inhibiting RSV viral load and improving the pulmonary microenvironment in RSV-infected mice. Both antiviral and anti-inflammatory experiments had confirmed that the pharmacological activity of Res NPs is superior to that of Res. This suggested that nanosizing Res was an effective way to enhance the original pharmacological activity of Res and also offered a new formulation strategy for treating viral pneumonia.

Boron substitution in silicate bioactive glass scaffolds to enhance bone differentiation and regeneration

Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone regeneration and mineralization in vitro and in vivo, in comparison to silicate 1393. Both scaffolds supported human adipose stem cells proliferation, either in direct contact for the 1393, or mainly around for the 1393B20. Similarly, both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. In addition, these scaffolds supported bone regeneration and osteoclast/osteoblast activity in vivo in critical-sized rat calvarial defect. Nevertheless, mineralization and collagen formation were significantly enhanced for the 1393B20, at 3-months post-implantation, assigned to faster and more complete dissolution of the scaffolds. Thus, 1393B20 demonstrates greater promise for bone tissue engineering certainly due to its time-controlled release of boron and silicon. Statement of significanceBioactive glasses (BAGs) show great promise in bone tissue engineering as they effectively bond with bone tissue, fostering integration and regeneration. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. Both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. The presence of boron in the 1393B20 enhanced mineralization and collagen formation in vivo compared to 1393, probably due to its faster dissolution rate. Here, 1393B20 demonstrated greater promise for bone tissue engineering compared to the well-known 1393 BAG.

Formulation and Evaluation of Lamotrigine Spherules with Robust Gelation Technique

Many freshly created high-potential medications have low water solubility, which is a challenge in formulation development. The study aimed to improve the solubility of Lamotrigine, a weakly soluble medication classified as BCS class II, by solid dispersion techniques. Lamotrigine solid dispersion was created using the solvent evaporation method, and the formulation was assessed using stability tests, Fourier transform infrared spectroscopy (FTIR), and physical properties. Preformulation investigations yielded satisfactory results, therefore pellets were formed and evaluated. Solid dispersion had a different pharmacokinetic profile than pure medication, which could be attributable to Lamotrigine's faster dissolution rate from solid dispersion

Controlled dissolution of physically cross-linked locust bean gum – κ-carrageenan hydrogels

Most hydrogels swell but do not dissolve in water since their chains are tied to each other. Nevertheless, some hydrogels disintegrate under physiological conditions, a property that could be beneficial in emerging applications, including sacrificial materials, 3D bioprinting, and wound dressings. This paper proposes a novel approach to control the dissolution rate of hydrogels based on the integration of kappa carrageenan nanoparticles (KCAR-NPs) into kappa carrageenan (KCAR) and locust bean gum (LBG) hydrogels to obtain a three-component hybrid system. KCAR and LBG are known to have synergistic interactions, where physical interactions and chain entanglements lead to their gelation. We hypothesized that integrating the bulky nanoparticles would disturb the three-dimensional network formed by the polysaccharide chains and enable manipulating the dissolution rate. Compression, water absorption, rheology, and cryo-scanning electron microscopy measurements were performed to characterize the physical properties and structure of the hydrogels. The hybrid hydrogels displayed much faster dissolution rates than a control system without nanoparticles, which did not completely dissolve within 50 days and offered a cutting-edge means to finely adjust hydrogel dissolution through modulation of KCAR and KCAR-NPs concentrations. The new hydrogels also exhibited shear-thinning and self-healing properties resulting from the weak and reversible nature of the physical bonds.

Solubility and Dissolution Rate Enhancement of Aceclofenac by Solid Dispersion Employing Kneading and Solvent Evaporation Techniques

Background: Aceclofenac (ACF) is a non-steroidal anti-inflammatory drug with potent anti-inflammatory and analgesic properties. ACF is belongs to BCS class II which has poor solubility in water (practically insoluble) and high permeability that leads to a low dissolution rate and reduced bioavailability. Objective: to enhance the solubility and dissolution rate of ACF using the solid dispersion method (SD) by two common techniques which were solvent evaporation (SE) and kneading (Kn) by using different carriers Mannitol, PVP k30, Soluplus®, and Urea in both techniques at 1:1 and 1:5 wight ratio. Methods: The effects of type of carrier and preparation method on solubility and dissolution rate of SD were studied. Solid dispersions were characterized for their, percentage yield, drug content, drug solubility and in-vitro dissolution rate in comparison with pure drug. Results: The best formula is obtained by the Kn formula (F16) which was formulated by the use of ACF: Soluplus®: with a weight ratio of 1:5 which gave a high percentage yield (99.5%), high drug content (99.8± 0.003%) and the best solubility enhancement which was 361 folds compared to pure ACF and faster dissolution rate which was 80% in 10 minutes compared to 20% for pure drug. Conclusion: the solubility and in-vitro dissolution rate of ACF was efficiently improved when prepared by SD techniques, utilizing both solvent evaporation and kneading methods. Furthermore, the kneading method was superior to solvent evaporation method due to the greater enhancement of solubility and dissolution rate obtained by all carriers and ratios with higher improvement by 1:5 ratio, and can be considered a successful and efficient strategy for solubility and in-vitro dissolution rate improvement of hydrophobic drugs.

Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate

ABSTRACT Objective Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems. Methods Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure. Results P4 SLNs achieved a deeper diffusion depth of 180 μm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 μm). The in vivo experiments demonstrated that P4 SLNs had a T1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T1/2 of 13.12 h. Conclusions This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

Improving cellular uptake and synergetic anti-tumor effects of magnolol and Brucea javanica oil through self-microemulsion

Objective Magnolol (MG) and Brucea javanica (L.) Merr. oil (BJO) possess synergetic anti-tumor effects, but have poor water solubility and stability, which results in low oral bioavailability. Significance The MG loaded self-microemulsion drug delivery system (MG-SMDDS) with BJO as oil phase component was utilized to improve the cellular uptake and synergetic anti-tumor effects. Methods Compatibility study and pseudoternary phase diagram (PTPD) were respectively employed to screen for the composition and proportion of oil phase in the formulation. Central composite design-effect surface method was applied to optimize proportion of each formulation condition. The droplet size, ζ-potential, colloid stability, encapsulation rate (ER) and in vitro dissolution rate of MG-SMDDS were evaluated. Furthermore, cellular uptake and cytotoxicity of the microemulsion on HepG2 cells were assessed. Results The optimal composition of MG-SMDDS was: MG (9.09%), castor oil (7.40%), BJO (2.47%), Cremophor EL 35 (54.04%) and 1, 2-propanediol (27.01%). The MG-SMDDS exhibited satisfactory droplet size, ζ-potential, colloid stability and ER, as well as faster dissolution rate than free MG. More importantly, SMEDDS containing BJO could enhance the cellular uptake and cytotoxicity of free BJO and free MG on tumor cells. Conclusions The BJO self-microemulsion delivery technique can provide an idea for design of oral delivery vehicles based on BJO.

Hydrodynamics and mass transfer performance of microbubble flow in the bubble column with a contraction section

Bubble columns have many applications in the biochemical, petrochemical, and metallurgical industries. The gas-liquid system composed of microbubbles is characterized by significant phase interfacial area, high mass transfer efficiency, fast dissolution rate, strong adsorption capacity, and long self-sustaining time. This paper investigated the performance of pressurized dissolved gas microbubble generation (PDG) using a Venturi tube as the releaser using a plug-in online imaging instrument. The hydrodynamic and mass transfer characteristics of the microbubble flow generated by PDG in a bubbling column with a contraction section (BCS) were then investigated. One of the primary studies was the effect of the contraction section on the flow performance of the bubbles, the mass transfer performance, and the aeration efficiency of the PDG versus the throat inlet Venturi bubble generator (VBG). The results show that the initial bubble Sauter mean diameter is essentially constant with dissolved gas pressure, and the bubble size distribution(BSD) is similar. The bubble stream passing through the contraction section exhibits two different BSD at the center and side walls of the BCS outlet section. Microbubbles in the inlet section in the absence of external forces almost do not occur in bubble coalescence. The flow of bubbles in the contraction section is subject to a slight coalescence effect. The diameter of bubbles in the contraction section is mainly larger than 20 μm. In the contraction section, coalescence occurs mainly at the side wall. The way of occurrence is adsorption coalescence and collision coalescence. The bubbles move in a gradually confined space with a high degree of interference with each other's bubbles, and the liquid linear velocity acts as an ‘external force’ that benefits the flow of the bubbles out of the confined space. The standard aeration efficiency of PDG is 3–11 times higher than that of the VBG. At 0.3 MPa, the highest standard aeration efficiency for the PDG method was between 0.18 and 0.64 kgO2/kW∙h.

Chalcopyrite Leaching in Ferric Sulphate: The Effect of Fe3O4-CuFeS2 Galvanic Couple on the Cu Dissolution

Galvanic interactions present alternative strategies to achieve a more efficient Cu dissolution from CuFeS2. The present work studied the interaction between chalcopyrite–magnetite (CuFeS2-Fe3O4) in acidified ferric sulphate Fe2(SO4)3-H2SO4 at a solution pH of 1.8 and a temperature of 25 or 50 °C. The addition of Fe3O4 to CuFeS2 forms a galvanic couple, which positively impacts the dissolution of Cu. The results showed that the presence of Fe3O4 led to high and fast Cu dissolution rates and decreased significantly the activation energy, from 83 to 57 kJ/mol. In addition to that, the solid residues revealed that CuFeS2 dissolution produced intermediate Cu-S-rich phases: CuS, Cu2S and Cu5FeS4, which appeared to envelop CuFeS2, had no observable intermediate phase while in the presence of Fe3O4. The results showed that 94% of Cu could be recovered after 5 h of leaching at 50 °C at a Fe3O4/CuFeS2 ratio of 4:1 and a 460 mV Ag/AgCl solution potential. The findings of this study present an option for efficient Cu dissolution from CuFeS2 in ferric sulphate at atmospheric pressure.

Influencing mechanism of visible light and silver ions on p- and n-type chalcopyrite bioleaching

Different effects and mechanisms of visible light and silver ions (Ag+) on the bioleaching of p- and n-type chalcopyrite (Cpy A and Cpy B, respectively) in the presence of Acidithiobacillus ferrooxidans were investigated. The semiconductor characteristics, bioleaching behaviors, surface morphologies, main phases and surface species of chalcopyrite were evaluated by Hall effect test, bioleaching tests, X-ray diffraction, scanning electron microscope and X-ray photoelectron spectroscopy. According to the results, Cpy A had a higher carrier concentration and greater carrier mobility than Cpy B, resulting in a faster dissolution rate. After 24 d of bioleaching, the copper extraction rate of Cpy A was 91.05%, which was 17.86% higher than that of Cpy B (73.19%) when light illumination and Ag+ existed together. Obviously, visible light and Ag+ promoted the bio-dissolution process of Cpy A more strongly than Cpy B, which was mainly attributed to the higher carrier mobility in Cpy A. Furthermore, charge transfer occurred more rapidly on the chalcopyrite surface when illuminated, and more Ag2S was accumulated, especially for Cpy A. As a result, the dense structure of the passivation layer was destroyed, reducing the passivation effect and promoting chalcopyrite dissolution.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O2-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O2-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2-GeMs. In vivo evaluation confirmed robust insertion and positioning of O2-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

Enhancement of particle properties of cefuroxime sodium by simultaneous control of polymorph and uniform spherulites

Cefuroxime Sodium (CS) is a low-toxicity and highly effective antibiotic drug with a wide application market. Its polymorph form β has the advantage of thermal stability and resistance to degradation. However, poor powder properties cause filtration difficulties, severe electrostatic phenomena and difficulties in automated dispensing, which limit its application. In order to improve the powder properties and stability of CS from the source, we used a one-step crystallization method to prepare CS (form β) with high sphericity and uniform particle size. The spherulites of form β of CS (β spherulites) have excellent powder properties, with high flowability (32.8°), good sphericity (90.2%), low C.V. (45.6%), and adjustable particle size distribution. Thanks to improved powder properties, the β spherulites exhibits 40% higher thermal stability and maximum 41% faster dissolution rate in the compatible solutions, compared to commercially available products, which implies the β spherulites is more competitive in powder formulations.

Reactive Transport Modelling of carbon mineralization – a machine learning-based approach

Carbon mineralisation is currently one of the most promising Carbon Capture and Storage (CSS) options for permanent gas sequestration since it ensures a rapid conversion of carbon from the gas phase to a carbonate mineral. Mafic and ultramafic rocks are the best geological options for mineral carbonation due to the relatively fast dissolution rates of the mineral components that can release carbonatable divalent cations such as Mg2+, Sr2+, Ba2+, Mn2+, Ca2+ and Fe2+. Once in solution, these cations react with dissolved carbonate ions to form, under convenient pH and temperature conditions, carbonate minerals like calcite, magnesite, siderite, rhodochrosite, or dolomite.
 The viability of carbon mineralization with injection of freshwater has been proven in the CarbFix project [1]. The main feature of the CarbFix method is that CO2 (and other minor gases) is not injected under its gaseous form but already dissolved in an aqueous fluid, which greatly enhances the mineralisation rates. The methodology, however, requires vast amounts of water that can be a limited resource in many regions. Seawater may be the most viable water source for underground carbonation in many areas, but its use raises questions on the efficiency of the carbonation process. The high ionic strength of seawater makes the geochemical interactions between CO2-rock and seawater more complex and, so far, more unpredictable. Reactive transport modelling (RTM) based on experimental thermodynamic and kinetic data of seawater-basalt interaction [2, 3] can shed some light on the expected mineralisation progress in sites with different mineralogy and variable temperature conditions. Figure 1 shows the results obtained with a reactive transport model that simulates the injection of CO2-charged seawater in basaltic rock.
 geochemical reaction calculations in particular might be considerably slow and are sometimes redundant as they might be based on a very similar set of input values. These challenges are usually faced by introducing a number of simplifications in the models to meet the objectives of the simulation studies. Thus, alternative ways to solving the full system are a priori a potential way to reduce the computational burden of numerical models.
 One of such alternatives is Machine Learning (ML) and, more specifically, Artificial Neural Networks (ANN), which are inspired on biological neural networks as the ones found in the human brain. They contain several computational “neurons” arranged in different layers. Each of these neurons can be activated based on the response of the other connected neurons. The training process consists of feeding data into the ANN and fitting the connection weights between the neurons to reproduce and learn the hidden relationships of the data. Recently, the authors have coupled ANNs of a geochemical system into a reactive transport simulator [5]. In this approach, Supervised Machine Learning with ANNs is used to accurately predict the geochemical evolution in a reactive transport framework without the need of actually performing the (expensive) chemical equilibrium calculations in the reactive transport model.
 The goal of this work is to apply and further develop the technology based on Supervised Machine Learning algorithms to drastically boost the efficiency of reactive transport models of carbon mineralization in the Carbfix system [6]. Firstly, a set of geochemical models of CCS are developed in batch systems (0D) as well as reactive transport models in 1D axisymmetric, 2D, and 3D RTM modelling with different degrees of complexity. Modelling focuses on the injection of CO2-charged seawater into basaltic rocks. In this system, CO2 is consumed via a two-step reaction: (1) Dissolution of Basaltic Glass and release of cations (Ca and Mg), and (2) precipitation of Ca-Mg carbonates and other secondary minerals. The RTM models consider a 1 km domain and a characteristic mineralization of 3-4 years. As a first step, these models are solved with the convential (non ML-based) reactive transport simulator iCP [7]. Then, ANNs are trained and validated with the latest developments in setting up neural networks and used to solve these RTM systems with a Comsol-ML library. The resulting ANNs present good accuracies with coefficients of determination (R2) above 0.95 for all outputs, and a batch calculation speedup of 30 as compared to traditional chemical equilibration with PhreeqC. Preliminary results of RTM using ML to predict the chemical step indicate a speedup of on order of magnitude and reasonable accuracy as compared to conventional RTM. Our results demonstrate that it is conceivable to replace a geochemical solver in a RTM environment with significantly faster surrogate-based models powered by a machine learning algorithm

Experimental determination of the reactivity of basalts as a function of their degree of alteration

The element release rates from naturally altered basalts were measured in batch experiments at 27 °C, and in mixed-flow experiments at 25 °C in reactive fluids initially consisting of pH 3 or 4 aqueous solutions. The basalts reacted in this study consist of 1) surface weathered basalts ranging in age up to 13 million years, and 2) hydrothermally altered basalts from zeolite to actinolite alteration zones (temperatures of ∼50 to 300 °C). The in situ pH in the batch experiments increased over time with the final pH of the fluids ranging from to 4 to 8. Most experiments exhibited a preferential release of Ca and Mg compared to Si from the dissolving basalts, both initially and over the long-term. This behavior is attributed to the combination of an initial rapid cation-proton exchange reaction and the relatively fast dissolution rates of Ca-bearing minerals. The BET surface area normalized Si release rates for all of the altered basalts are within one order of magnitude of each other, and from one to two orders of magnitude lower than corresponding rates from fresh basaltic glass and fresh crystalline basalts. This is interpreted to stem from 1) the fast removal of reactive basaltic glass and olivine from fresh basalts during the natural alteration of the rocks, 2) the similarity of the dissolution rates of the remaining albitic plagioclase, pyroxenes, epidote, and zeolites, and 3) the high surface areas of some less reactive secondary minerals such as clays. Overall, the results suggest that altered basalts will be effective in consuming CO2 during both natural and engineered processes, though at a somewhat slower rate than unaltered basalts.

Precipitation Mechanism of VOSO4 in Oversaturated Electrolytes of the Solid-Liquid Storage Method in Vanadium Redox Flow Batteries

Redox flow batteries (RFBs)-based storage systems have the unique feature of separate power generating and energy storage units that can be individually sized. RFBs can be used for days-long energy storage, but because of the low solubility of most ions and molecules in both aqueous and non-aqueous solvents,[1,2] scaling these RFB systems for days-long applications requires a lot of storage tanks and floor area. Our team has developed a new storage method that can significantly increase energy storage density while still maintaining the traditional flow battery design.[3] This method involves storing the reactants in both soluble ions and undissolved solid form, and only the liquid containing the soluble ions is circulated through the batteries. A larger than 4X improvement in storage energy density may be achieved with this strategy. The feasibility of this method was demonstrated in a hydrogen-vanadium (VI/V) RFB.[4] From the study, a major factor in achieving high performance with this hybrid storage system is the rates of the precipitation of the saturated electrolyte and dissolution of the solid precipitate. It was discovered that not all vanadium sulfate solids have precipitation rates fast enough to generate the active ions at the rate needed in the electrode reaction. Only the low crystallinity solid generated by rapid precipitation by the use of a suitable nucleation material was found to have the dissolution rate needed. This presentation will discuss the role of the molecule structures and the mechanism of the precipitation process in the formation of solids that have slow and fast dissolution rates.

Submicron polymer particles loaded with piperine: Preparation from fucoidan and evaluation of morphology, release profile, and antioxidant activity

A combination of two methods, polyelectrolyte self-assembly of fucoidan–chitosan and isocyanide-based multicomponent reactions, was used to obtain submicron polymer particles suitable for lyophilization. Piperine, an alkaloid and the major bioactive compound found in black pepper, is endowed with numerous biological activities; however, its application is hindered by low solubility and poor delivery. To overcome this problem, piperine was loaded into the submicron polymer particles obtained. These particles were subjected to lyophilization to assess their ability to redisperse in aqueous solution after drying and their stability. The characterization of the nanoparticles by dynamic light scattering revealed particle sizes of 219.67 ± 0.61 and 355.63 ± 14.49 nm for fucoidan–chitosan nanoparticles and piperine-loaded nanoparticles, respectively. Also, an irregular spherical piperine-loaded nanoparticle was found using atomic force microscopy. An encapsulation efficiency of 92.78% ± 0.02% was measured with UV/visible spectroscopy. In vitro, the release profile of piperine from the nanoparticles showed a significant release and faster dissolution rate than free piperine. For the release mechanism of piperine from the nanoparticle, the Korsmeyer–Peppas model was the best fit with a correlation coefficient (R2) close to 1. The antioxidant activity of the piperine-loaded nanoparticles was significantly higher than that of the unformulated piperine. The piperine-loaded nanoparticles also exhibited positive stability against stress from lyophilization. Therefore, fucoidan–chitosan nanoparticles to improve the bioavailability of piperine, as well as enhance antioxidant activity, and could be used as a nutraceutical.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅲ): classification of granule dissolving behaviors

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

New Mg/Sr phosphate bioresorbable glass system with enhanced sintering properties

Phosphate glasses are ideal candidates to substitute traditional silicate bioactive glasses as they can exhibit controlled ion release. Furthermore, phosphate glasses possess congruent dissolution and also resistance to crystallization, two properties that are favorable for the processing of 3D porous scaffolds. However, most of the phosphate glasses also exhibit a fast dissolution rate, which is inappropriate for bone tissue regeneration. In this context, a new bioresorbable phosphate glass within the 45P2O5- 2.5B2O3- 2.5SiO2- 10Na2O- 20CaO- (20-x) SrO- (x)MgO (in %mol) composition was developed. Magnesium is substituted for strontium in order to promote bone formation but in the present study, its role is mainly to favor sintering at lower temperatures without crystallization. The in vitro dissolution in simulated body fluid was assessed for glass particles <38 μm (pH, ICP, SEM-EDS). All glasses were found bioresorbable, rather than bioactive. The newly developed phosphate glasses containing Sr and Mg were found to have a slower dissolution rate when compared to traditional metaphosphate glasses while maintaining their congruent dissolution and hot forming ability. All glasses were 3D printed into scaffolds with controlled pore size and without apparent crystallization. The substitution of SrO for MgO was shown to be highly effective in enhancing the sintering ability of the material by enabling sintering at lower temperatures while avoiding the risk of crystallization leading to the processing of scaffolds with mechanical properties, in compression, above that of the cancellous bone.

3D Printed Flavor-Rich Chewable Pediatric Tablets Fabricated Using Microextrusion for Point of Care Applications.

Over the past few years, 3D printing technologies have gained interest in the development of medicinal products for personalized use at the point of care. The printing of drug products offers personalization and flexibility in dose, shape/design, and flavor, potentially enhancing acceptability in pediatric populations. In this study, we present the design and development of ibuprofen (IBU) chewable flavor-rich personalized dosage forms by using microextrusion for the processing of powdered blends. The optimization processing parameters such as applied pneumatic pressure and temperature resulted in high quality printable tablets of various designs with a glossy appearance. Physicochemical characterization of the printed dosages revealed that IBU was molecularly dispersed in the methacrylate polymer matrix and the formation of H bonding. A panelist's study demonstrated excellent taste masking and aroma evaluation when using strawberry and orange flavors. Dissolution studies showed very fast IBU dissolution rates of more than 80% within the first 10 min in acidic media. Microextrusion is a 3D printing technology that can be effectively used to generate pediatric patient centric dosage forms at the point of care.

Insight into the mechanism behind oral bioavailability-enhancement by nanosuspensions through combined dissolution/permeation studies

As numerous new drug candidates are poorly water soluble, enabling formulations are needed to increase their bioavailability for oral administration. Nanoparticles are a conceptually simple, yet resource consuming strategy for increasing drug dissolution rate, as predicting in vivo oral absorption using in vitro dissolution remains difficult. The objective of this study was to obtain insight into nanoparticle characteristics and performance utilizing an in vitro combined dissolution/permeation setup. Two examples of poorly soluble drugs were examined (cinnarizine and fenofibrate). Nanosuspensions were produced by top-down wet bead milling using dual asymmetric centrifugation, obtaining particle diameters of approx. 300 nm. DSC and XRPD studies indicated that nanocrystals of both drugs were present with retained crystallinity, however with some disturbances. Equilibrium solubility studies showed no significant increase in drug solubility over the nanoparticles, as compared to the raw APIs. Combined dissolution/permeation experiments revealed significantly increased dissolution rates for both compounds compared to the raw APIs. However, there were substantial differences between the dissolution curves of the nanoparticles as fenofibrate exhibited supersaturation followed by precipitation, whereas cinnarizine did not exhibit any supersaturation, but instead a shift towards faster dissolution rate. Permeation rates were found significantly increased for both nanosuspensions when compared to the raw APIs, indicating a direct implication that formulation strategies are needed, be it stabilization of supersaturation by precipitation inhibition and/or dissolution rate enhancement. This study indicates that in vitro dissolution/permeation studies can be employed to better understand the oral absorption enhancement of nanocrystal formulations.