Surface Of Carrier Particles Research Articles

Impact of carrier particle surface properties on drug nanoparticle attachment

HypothesisThe stabilization and isolation to dryness of drug nanoparticles has always been a challenge for nano-medicine production. In the past, the use of montmorillonite (MMT) clay carrier particles to adsorb drug nanoparticles and maintain their high surface area to volume ratio after isolation to dryness has proven to be effective. We hypothesise that the distribution of hydrophilic and hydrophobic patches on the clay’s surface as well as its porosity/roughness, hinder the agglomeration of the drug nanoparticles to the extent that they retain their high surface area to volume ratio and display fast dissolution profiles. ExperimentsIn this work, the distribution of hydrophobicity and hydrophilicity, and the porosity/roughness, of the surface of selected silica carrier particles were varied and the impact of these variations on drug nanoparticle attachment to the carrier particle and subsequent dissolution profiles was studied. FindingsThe fastest dissolution profiles at the highest drug nanoparticle loadings were obtained with a periodic mesoporous organosilane carrier particle which had a homogeneous distribution of hydrophobic and hydrophilic surface properties. Carrier particles with rough/porous surfaces and a combination of hydrophobic and hydrophilic patches resulted in nanocomposite powders with faster dissolution behaviour than carrier particles with predominantly either a hydrophobic or hydrophilic surface, or with non-porous/smoother surfaces.

Precipitative Coating of Calcium Phosphate on Microporous Silica–Titania Hybrid Particles in Simulated Body Fluid

Titania and silica have been recognized as potential drug delivery system (DDS) carriers. For this application, controllable biocompatibility and the suppression of the initial burst are required, which can be provided by a calcium phosphate (CP) coating. However, it is difficult to control the morphology of a CP coating on the surface of carrier particles owing to the homogeneous nucleation of CP. In this study, we report the development of a CP-coating method that homogeneously corresponds to the shapes of silica–titania (SiTi) porous nanoparticles. We also demonstrate that controlled surface roughness of CP coatings could be achieved in SBF using SiTi nanoparticles with a well-defined spherical shape, a uniform size, and a tunable nanoporous structure. The precipitation of CP was performed on mono-dispersed porous SiTi nanoparticles with different Si/Ti molar ratios and pore sizes. The pore size distribution was found to significantly affect the CP coating in SBF immersion; the surfaces of the nanoparticles with bimodal pore sizes of 0.7 and 1.1–1.2 nm became rough after CP precipitation, while those with a unimodal pore size of 0.7 nm remained smooth, indicating that these two pore sizes serve as different nucleation sites that lead to different surface morphologies.

The influence of relative humidity on the carrier particle surface characteristics used in dry powder inhalation formulation

Purpose: Investigation of the effect of carrier storage at elevated relative humidities on the carrier surface fines. The resulted effects of this storage conditions on the carrier surface characteristics when mixed with micronized salbutamol sulphate and the subsequent in vitro deposition were investigated. Methods: Lactose (InhaLac120) and mannitol (Pearlitol160) carrier particles (112 µm – 140 µm) were subjected to different relative humidities for 6 weeks period of time in order to get a smoother surface. In vitro deposition carried out for those modified carriers after mixing with salbutamol sulphate using a Next Generation Impactor (NGI). The modified carriers were characterized by scanning electron microscope, Brunauer Emmet and Teller specific surface area determination, differential scanning calorimetry, X-ray powder diffraction and water vapour sorption in comparison with the treated carrier without added fines. Results: The modified lactose and mannitol carriers stored at different relative humidities starting from 35% RH-75% RH show no change in fine particle fraction (FPFs). Subsequently, the carrier storage at 95% RH shows a significant decrease in the in vitro drug release. This probably by increasing drug-carrier adhesion and show a difficult detachment of the drug particles from the carrier surface smoothed at 95% RH. Conclusions: Storage of lactose and mannitol carriers at different relative humidities up to 75% result in un-significant change in drug fine particle fraction using the NGI. Additionally, storage of those carriers at high relative humidity up to 95% RH found to decrease significantly the dispersion of the drug and subsequently the FPF in the in vitro deposition test.

Stability of spouted bed during spray cold coating on the surface of carrier particles

Abstract The rapid freezing of droplets on the surface of cold carrier particles can reduce the spray freeze-drying time. The coating freezing process can be treated in batch by using a spouted bed and the bed stability is the key. The freezing process of droplets would agglomerate the carrier particles. By analyzing the standard deviation of the bed pressure drop and the fluctuation of the bed pressure, the stable operating conditions of the spouted bed under cold coating were studied, and a dynamic adjustment method of the inlet air velocity to maintain stable spouting was proposed. The results show that the stable operating air velocity range can be described useing the standard deviation of pressure fluctuations. Before bed collapse occurs, it will experience an unstable spouting process, which causes the bed pressure to fluctuate a standard deviation of less than 15 Pa after more than 40 Pa.

Modification of the zeta potential of montmorillonite to achieve high active pharmaceutical ingredient nanoparticle loading and stabilization with optimum dissolution properties

Nanoparticles (NPs) of three poorly water-soluble BCS class II active pharmaceutical ingredients (APIs) (clozapine (CLO), curcumin (CUR) and carbamazepine (CBMZ) with zeta potentials –28.5 ± 2.5, –33 ± 1.5 and –13 ± 1.5 mV respectively) were produced, stabilized and isolated into the solid state with the help of Montmorillonite (MMT) clay carrier particles. The nanoparticles of clozapine (27 nm), curcumin (170 nm) and carbamazepine (30 nm) were produced and stabilized in suspension using a reverse antisolvent precipitation technique in the presence of ‘as received’ MMT carrier particles (∼30 μm) and/or MMT carrier particles whose surface had been slightly modified with a cationic protein, protamine sulphate salt (PA). The resulting nanoparticle carrier composites were isolated directly from suspension into a solid state form by simple filtration followed by air-drying. The API dissolution rates from these dried NP-carrier composites were comparable with those of the respective stabilized API nanoparticles in suspension up to maximum CLO, CUR and CBMZ loadings of 23%, 21.8% and 33.3% (w/w) respectively, although surface modification of the MMT carrier particles with PA was needed for the CLO and CUR NP-carrier composites in order to preserve the fast API nanosuspension-like dissolution rates at higher API loadings. For both of these APIs, the optimal loading of PA on MMT was around 4 mg/g, which likely helped to limit aggregation of the API nanoparticles at the higher API loadings. Interestingly, no MMT surface modification was needed to preserve fast API dissolution rates at higher API loadings in the case of the CBMZ NP-carrier composites. This discrimination among the three APIs for carrier particle surface modification was previously observed in reported studies by our group for three other APIs, namely valsartan, fenofibrate and dalcetrapib. When examined together, the data for all six APIs suggest a general trend whereby API nanoparticles with zeta potentials more positive than around −25 mV do not require carrier particle surface modification with PA in order to preserve their fast dissolution rates from NP-carrier composites at higher API loadings. Thus, this study offers a potentially effective means of transforming poorly water soluble BCS Class II APIs into fast dissolving solid dosage NP-carrier composites, whereby the surface properties of the carrier particle can be tuned with prior knowledge of the zeta potential of the API nanoparticles.

Characteristics of microalgae gasification through chemical looping in the presence of steam

As a novel gasification technology, chemical looping gasification (CLG) was considered as a promising technology in solid fuel gasification. In this work, CLG was applied into microalgae, and the characteristics of syngas production and oxygen carrier in the presence of steam were obtained through experiments in a fixed bed reactor. The results showed that the partial oxidation of oxygen carrier improved the gasification efficiency from 61.65% to 81.64%, with the combustible gas yield of 1.05 Nm3/kg, and this promotion effect mainly occurred at char gasification stage. Also, an optimal Fe2O3/C molar ratio of 0.25 was determined for the maximum gasification efficiency. 800 °C was needed for the gasification efficiency over 70%, but excess temperature caused the formation of dense layer on oxygen carrier particle surface. Steam as gasification agent promoted syngas production, but excess steam decreased the gasification efficiency. Steam also enhanced the hydrogen production by the conversion of Fe/FeO into Fe3O4, avoiding the intensive reduction of oxygen carrier. The Fe2O3 oxygen carrier maintained a good reactivity in 10th cycle while used for microalgae CLG. The results indicated that CLG provided a potential route for producing combustible gas from microalgae.

CARS microscopy as a tool for studying the distribution of micronised drugs in adhesive mixtures for inhalation

Drug particles can be produced in the proper aerodynamic particle size distribution (PSD) for inhalation by techniques such as micronisation or spray drying (1–5 µm). However, mixing with coarse carrier particles may change the PSD by agglomeration. Furthermore, the spatial distribution of the drug particles on the carrier particles in adhesive mixtures is highly relevant to the dispersion performance of inhalation powders. Coherent anti‐Stokes Raman scattering (CARS) microscopy is capable of chemically selective imaging, allowing the distribution of drug particles on the surface of carrier particles to be visualised. We used CARS microscopy to image the drug distribution for budesonide and salmeterol on the surface of lactose carrier particles. Image analysis was performed to determine the drug PSD that was then compared with the PSD obtained from laser diffraction. Additionally, comparative CARS and scanning electron microscopy (SEM) images were recorded to allow a direct comparison of the images obtained from CARS microscopy and from SEM. CARS microscopy revealed the drug to be in clusters on the surface of the carrier particles, while the image analysis identified 68% of the particles to have a median area of 0.4 µm2. Image analysis resulted in measurement of larger particles than laser diffraction, which may be caused by agglomeration during mixing. The combined chemical and morphological information from comparative CARS and SEM analysis resulted in unambiguous identification of the spatial drug distribution over the carrier surface. Our results indicate that CARS microscopy is a useful tool to study adhesive mixtures for inhalation. Copyright © 2014 John Wiley & Sons, Ltd.

Surface roughness effects on the tribo-charging and mixing homogeneity of adhesive mixtures used in dry powder inhalers

For active pharmaceutical ingredients (APIs) delivered to the lung it is of main importance that they reach the deeper lung, in order to cause the intended therapeutic effect. To obtain inhalable powders that on the one hand are small enough to travel along the tiny airways finally reaching their target site and on the other hand show sufficient flowability, so-called adhesive mixtures are used. They consist of API particles in the size range of 0.5μm–5μm and carrier particles in the size range of 50μm–200μm, that, due to the size of the carrier, exhibit adequate flowability. However, when administered to the patient, the API has to separate from the carrier surface in order to be able to penetrate the deep lung. The performance of dry powder inhalers (DPIs) and adhesive mixtures is mainly governed by interparticle forces like Van der Waals and triboelectric forces. Carrier surface roughness modification is a new method to alter the contact area and thus the Van der Waals forces between API and carrier. Unfortunately the tribo-charging during handling, especially during the generation of the adhesive mixtures in a tumble blender, is strongly influenced by particle characteristics like particle surface roughness. Thus the mixing quality and stability and thereby the usability of the powder mixture might be additionally influenced by tribo-charging. Therefore the aim of the present work is to investigate whether tribo-charging during the mixing process is influenced by the carrier particle surface roughness. Further the influence of tribo-charging on mixing homogeneity is assessed. Net charge measurements are performed using a Faraday cup. As model API and carrier salbutamol sulfate and spray dried mannitol are used respectively. It is shown that the carrier particle characteristics impact tribo-charging of the pure carriers in a tumble blender. This influence is not observed for the adhesive mixtures of carrier and API. Nevertheless the homogeneity of the adhesive mixtures is still influenced by the charging of the carriers.

Towards the optimisation and adaptation of dry powder inhalers.

Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model.

Determination of interparticulate forces in ordered powder mixes.

Abstract The theory of interparticle bond formation is considered with particular reference to ordered powder mixing. A technique is described for measuring the interparticle adhesion forces between drug and excipient particles bound in ordered units. The method uses a specially constructed ultracentrifuge rotor tube insert such that fine adherent particles can be separated from coarser carrier particles in ordered mixes. The ordered units are held behind a screen in the rotor tube insert and when the forces generated by ultracentrifugation become greater than the interparticle adhesion forces the ordered units break down into their component particles. Adhesion profiles were obtained for four different ordered mixes containing drug and excipient powders by plotting force of adhesion against the cumulative percentage of fine drug particles adhering to the carrier particle surface. The adhesion profile is influenced by the quantity of drug powder adhering to the excipient carrier particle surface. Above a critical drug content, each ordered mix shows a ‘composite' adhesion profile consisting of two distinct curves linked by a lag period. The initial curve, preceding the lag period, appears to correspond to loss of large amounts of weakly bound drug particles; after the lag period only relatively strongly adhered particles are removed and this phase occurs more gradually. The critical drug concentration is related to the surface properties of the excipient and drug particles which determine the strength of adhesion forces within an ordered unit.

Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked airway inflammation in rats

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.

Effect of Toner Charge on Developing Behavior in Two-Component Electrophotographic System by Discrete Element Method

The objective of this paper is to investigate the effect of toner charge on the developed toner mass in a two-component development process using the discrete element method. The behavior of toner particles having homogeneous charge (-40 to +140 μC/g) or distributed charges (which were measured in experimental work) were simulated. When toner particles had extremely large charge, they failed to adhere properly on the latent images, because only a few toners bridge the electric potential difference between the photoreceptor and the latent image. On the other hand, the adhesion force between toner and carrier was much larger than the electrostatic force under the conditions of smaller toner charge. Then, the toner particles could not fly to the latent image from the surface of carrier particles under the applied electric field. The adhered toner mass becomes large when the average charge is around 25-45 μC/g. In particular, homogeneous toner charge is better for printing with high efficiency.

Deposition of Palladium Nanodots of Controlled Size and Density onto Surface‐Modified SiO2 Particles by an Atmospheric Pressure CVS/MOCVD Process

AbstractA continuous gas‐phase process under atmospheric pressure for tailoring Pd/SiO2 catalyst particles is described and characterized. Emphasis is placed on controlling the size and number density of Pd nanodots on the surface of the carrier particle. In the first step, sub‐micrometer‐sized SiO2 support particles are generated continuously in a flow reactor by chemical vapor synthesis (CVS) from tetraethyl(ortho)silicate (TEOS). A process‐integrated method is described to vary the surface concentration of hydroxyl groups on the SiO2 between about 1 and 6 OH groups per nm2, by adjusting the synthesis conditions. In a second step, Pd nanodots are deposited onto the SiO2 by metal–organic (MO)CVD of Cp(allyl)Pd [(η3‐allyl)(η5‐cyclopentadienyl)palladium]. The median diameter of the Pd nanodots was varied between about 1.3 and 3 nm (σg ∼1.2) by adjusting the precursor concentration in the gas phase. It is shown that the number density of the Pd islands varied in proportion to the density of hydroxyl groups on the SiO2 in the range 0‐12 Pd islands per 100 nm2 of carrier particle surface.

Behavior of Charge Control Agent (CCA) in Two-Component Developer

The relationship between the charge control capabilities of CCA and its modes of existance in two-component developer was investigated. Trianilino-triphenyl-methane TATPM was used as a positive type CCA. The highest charge up speed and the largest amount of charge were observed on the CCA-free toner particles which were in contact with the carrier particle surface on which the fine TATPM particles were deposited. The amount of positive charge on the CCA-free toner particles caused by the externally added TATPM particles in a toner-carrier mixture was larger than that on the conventional pulverized toner particles in which almost all TATPM particles are in its inner part. The results show that, during the toner-carrier mixing process, fine TATPM particles were produced and deposited onto the carrier particle surface. Then, the TATPM particles moved to the toner particle surface. As a result, the contact charge generated between the fine TATPM particles and the carrier particle surface took the main part of the positive charge on the CCA-free toner particles. The amount of TATPM deposited on the carrier surface was determined by the absorption at 602 nm of the TATPM / ethanol solution extracted from the carrier/ethanol dispersion. The relationship between the amount of TATPM on carrier surface and amount of positive charge on the toner was discussed.

Evaluation of SCF-engineered particle-based lactose blends in passive dry powder inhalers

The objective of this study was to assess the performance of SCF-engineered budesonide and albuterol sulfate powder blends in passive dry powder inhalers (DPI) relative to micronized drug blends. A number of lactose grades for inhalation were screened and the appropriate carrier and drug-to-lactose blending ratio were selected based on drug content and emitted dose uniformity. Aerosol performance was characterized by Andersen cascade impaction. Blend formulations of SEDS (solution enhanced dispersion by supercritical fluids) budesonide and albuterol exhibited a significant drug content uniformity (7–9% RSD) improvement over micronized drug blends (16–20% RSD). Further, the SEDS formulations demonstrated higher emitted dose and reduced emitted dose variability (10–12% RSD) compared to micronized powders (21–25% RSD) in the Turbospin, albeit without significant enhancement of the fine particle fraction. In contrast, SEDS powders exhibited increased fine particle fractions over micronized blends in the Clickhaler; improvements were more pronounced with albuterol sulfate. The performance enhancements observed with the SEDS powders are attributed to their increased surface smoothness and reduced surface energy that are presumed to minimize irreversible drug–carrier particle interactions, thus resulting in more efficient drug detachment from the carrier particle surface during aerosolization. As demonstrated for budesonide and albuterol, SEDS may enhance performance of lactose blends and thus provide an attractive particle engineering option for the development of blend formulations for inhalation delivery.

A Numerical Simulation for Carrier Particle Behavior in Electrophotographic Magnetic Brush Development.

Combining motion analysis of granular material by Distinct Element Method (DEM) and magnetic field analysis by Boundary Element Method (BEM), a simulation program for analyzing carrier particle behavior on Magnetic Roll (MGR) in a developer unit is developed. Calculation load for magnetic field analysis is reduced very much by using BEM. Therefore we can calculate magnetic flux density distribution on carrier particle surface in detail and renewal the magnetic field according to carrier particle configuration. Consequently, we attain to simulating the formation and the behavior of magnetic brush.

Pulmonary deposition of lactose carriers used in inhalation powders

Dry powder dosage forms are generally formulated by mixing the micronized drug particles with the larger carrier particles. Lactose is a commonly used carrier. Carriers enhance the flowability of powder mixtures and therefore enable low dosing of active substances. During inhalation, the drug particles are dispersed from the surface of carrier particles. The aim of this study was to compare how different qualities of 99mTc-labelled lactose carrier systems deposit in the lungs. The sizes of the labelled and unlabelled α-lactose monohydrate particles were compared by using a laser diffraction method. Distribution of radiolabel between different particle size fractions was determined using the Andersen cascade impactor. The in vivo depositions of lactose carrier systems were investigated in ten healthy men using the technique of gammascintigraphy. In addition, redispersion of budesonide from the carrier materials was evaluated by using the Andersen cascade impactor. According to the validation data the particle size of the lactose carriers remained unchanged during the labelling process. Low pulmonary deposition varying between 2.5 and 3.3% was detected. Only a small amount of lactose was deposited in the lungs, thus pulmonary deposition is not a limiting factor for lactose selection. According to in vitro redispersion data the fine particle fraction of the delivered dose in the impactor varied between 10.3 and 26.0%. Thus, the redispersion of the budesonide particles can be altered by the properties of the carrier system.

The oral absorption of micro- and nanoparticulates: neither exceptional nor unusual.

This mini-review covers some of the historical and recent arguments over the experimental evidence on the uptake by and translocation from the intestinal mucosa of microparticulates after oral administration. It is concluded that there is now no dispute over the fact that this is a normal occurrence. Particulate uptake does take place, not only via the M-cells in the Peyer's patches and the isolated follicles of the gut-associated lymphoid tissue, but also via the normal intestinal enterocytes. Factors affecting uptake include particle size, surface charge and hydrophobicity and the presence or absence of surface ligands. The covalent attachment of lectin or invasion molecules to the surface of carrier particles leads to greater systemic uptake. Whether or not the route can be utilized for the routine administration of therapeutic agents which are not normally absorbed from the gut is not yet proven. Many studies show that 2-3% of the ingested dose of submicron particles can be absorbed. The increasing diversity of carrier systems, which includes dendrimers and liposomes, needs to be exploited fully. More also must be learned about the inter- and intra-subject variability of lymphoid tissue so that appropriate selectivity can be achieved through the design of specific carriers.