Effect of surface covering of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effect of the surface covering of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier surfaces were covered with sucrose tristearate (J-1803F) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with various particle surface conditions prepared by surface covering. These powder mixtures were aerosolized by a Jethaler), and the in vitro inhalation properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with uncovered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface covering lactose carrier were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. In vitro inhalation properties increased with the percentage of J-1803F added. Using this surface covering system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.     

Effects of surface processing of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effects of the surface processing of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate were investigated. Lactose carrier particles were processed using a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared, consisting of micronized salbutamol sulfate and coarse lactose carriers with various particle surface conditions prepared by surface processing. These powder mixtures were aerosolized by a Jethaler, and the in vitro inhalation properties of salbutamol sulfate were evaluated with a twin impinger. Compared with those of the powder mixed with unprocessed lactose carriers, the in vitro inhalation properties of the powder mixture prepared using the surface processed lactose carriers were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. The in vitro inhalation properties increased with the rotor rotation rate. Using this surface processing system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.     

Evaluation of flow properties of dry powder inhalation of salbutamol sulfate with lactose carrier

The effects of the flow and packing properties of a drug/carrier powder mixture on emission of drug adhering to the carrier from capsules and inhalation devices were investigated. Model powder mixtures were designed consisting of lactose carriers with different particle shapes were prepared by surface treatment and micronized salbutamol sulfate. These powder mixtures were aerosolized by a Spinhaler, and in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The flow properties of the mixed powders were evaluated by the Carr's flowability index (FI) and Hausner's ratio (HR). The packing properties of the mixed powders were determined employing the tapping method. Compared with the powder mixed with the untreated lactose carrier, the FI, HR, and the constant K in Kawakita's equation of the powder mixture prepared using the surface-treated lactose carrier were significantly different, showing that the flow and packing properties of the drug/carrier powder mixture were improved. Using this surface-treated system, the handling of the powder mixture when packing into capsules is improved, which is desirable for handling dry powder inhalants. The fraction (%) of drug emitted from capsules and devices (EM) and the FI of the powder mixture were correlated. As the flow properties improved, the outflow of the powder mixture from capsules and devices became easier, and emission of drug adhering on the carrier from capsules and devices improved. Improvement of the inhalation process, such as the drug particles emitted from the inhalation system, is valuable for increasing inhalation properties of dry powder inhalation.     

Effect of surface layering time of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effect of the surface layering time of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier particles were layered with vegetable magnesium stearate by physical mixing. In the present study, drug/carrier powder mixtures were designed consisting of micronized salbutamol sulfate and lactose carriers with various particle surface conditions prepared by surface layering. These powder mixtures were aerosolized by a Jethaler, and the in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with unlayered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface layering lactose carrier were significantly different, showing that the in vitro inhalation properties of the drug/carrier powder mixtures were improved. In vitro deposition properties (RP) increased with surface layering time. Using this surface layering system would thus be valuable for increasing the inhalation properties of dry powder inhalation.     

Preparation of dry powder inhalation by surface treatment of lactose carrier particles

An attempt was made to produce carrier particles for dry powder inhalations by the surface treatment of lactose particles with aqueous ethanol solution. Drug/carrier powder mixtures were prepared consisting of lactose carriers with different particle surface properties and micronized salbutamol sulfate. These powder mixtures were aerosolized by Spinhaler, and in vitro deposition properties of salbutamol sulfate were evaluated by twin impinger. The degree of adhesion between drug particles and carrier particles was determined by the ultracentrifuge separation method. In addition, the air jet sieve method was used to evaluate characteristics of the separation of drug particles from carrier particles in airflow. The average adhesion force (F50) between the surface-treated lactose carrier and drug particles was significantly lower than that of powder mixed with the untreated lactose carrier, indicating that the degree of separation (T50) of drug particles from carrier particles was improved when surface-treated lactose carrier was used. This resulted in an improvement of in vitro inhalation properties.     

Development of dry salbutamol sulfate powder with high inhalation performance independent of inhalation patterns

While dry powder inhalations are commonly used to treat pulmonary diseases, their clinical performance depends on patient inspiratory flow patterns. The purpose of this study was to develop a new powder with high and stable therapeutic performance for various patients. We applied the supercritical antisolvent (SCF) method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests of in vitro inhalation performance with a human inspiratory flow simulator revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled SS. When inspired, the unique structure seemed to be broken resulting in small fragments that could be delivered to the lungs. However, stability tests under physical stress showed tolerance for transportation and handling. In addition, optimization of the concentration of the SS solution applied to SCF method improved the in vitro inhalation performance of SS-SCF. These results indicated that a unique bulky SS powder prepared by the SCF method was useful for dry powder inhalation.     

Preparation of dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed

An attempt was made to produce carrier particles for dry powder inhalation with lactose carrier particles surface-coated using a Wurster fluidized bed. The lactose carrier particles were coated with lactose aqueous solution containing hydroxypropyl methyl cellulose (HPMC) as a binder using a Wurster coating apparatus. Drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers under various particle surface conditions. These powder mixtures were aerosolized by a Jethaler((R)), and the in vitro deposition properties of salbutamol sulfate were evaluated by a twin impinger. The in vitro inhalation properties of the powder mixture prepared using the coated lactose carrier differed significantly compared with those of the powder mixture prepared using the uncoated lactose carrier, indicating improvements in in vitro inhalation properties of sulbutamol sulfate. In vitro inhalation properties increased with the surface coating time. This surface coating system would thus be valuable for increasing the in vitro inhalation properties of dry powder inhalation with lactose carrier particles.     

High-performance liquid chromatography of lactose with evaporative light scattering detection, applied to determine fine particle dose of carrier in dry powder inhalation products

A method for quantification of the fine particle dose of lactose is described, using a hydrophilic interaction chromatography (HILIC) method and evaporative light scattering detection. The HILIC method used an aminopropyl column and a mobile phase consisting of acetonitril/water (80/20, v/v) for isocratic elution. Sensitive chromatography was obtained using a low concentration of water in the extraction solvent. The detection limit (RSD<10%) at an injection volume of 10 microL is 10 microg/mL. Linearity was obtained in the range of 10-80 microg/mL (R(2)>0.99). A relative standard deviation (RSD) of 0.5% (N=6) demonstrated good precision of the optimized method.     

Quantification of the surface morphologies of lactose carriers and their effect on the in vitro deposition of salbutamol sulphate

Application of the scanning probe microscopy technique for quantitative measurement of the surface roughness of lactose carriers was evaluated. The roughness values of four different lactose carriers were related to the in vitro deposition results of the drug, salbutamol sulphate. The rugosity values of the lactose carriers were represented by Ra values which were in the order of DCL-40>DCL-11>lactose 325M>lactose 200 M. In vitro deposition results using a twin impinger showed that rougher carrier surfaces generally allowed more drug particles to be emitted from the capsules and inhaler but the availability of the drug to stage 2 was reduced, as detachment of drug particles from the carrier surfaces was more hindered. There was an optimum Ra value for greater delivery of the drug particles to stage 2 of the twin impinger. A balance between adherence and detachment of the drug from the carrier surface was needed in order to optimize the delivery of a drug to the desired target sites using a dry powder inhaler.     

Engineered mannitol as an alternative carrier to enhance deep lung penetration of salbutamol sulphate from dry powder inhaler

In this research mannitol particles were prepared by recrystallisation using non-solvent precipitation technique to investigate the effect of engineered carrier particles on their physicochemical properties and the in vitro deposition profiles of a model drug (salbutamol sulphate (SS)) from a dry powder inhaler (DPI). To this end, mannitol aqueous solution (15%, w/v) was added to different ratios of ethanol:water (100:0, 95:5, 90:10 and 85:15) to obtain mannitol particles. These crystallised mannitol particles were analysed in terms of micromeritic properties, morphology, DSC, FT-IR, and in vitro fine particle fraction (FPF) and emitted dose (ED) of SS. The results showed that the elongation ratio of all the recrystallised mannitol batches was higher than the original material giving them a needle-shaped morphology. Salbutamol sulphate deposition profiles from DPI formulation containing recrystallised needle-shaped mannitol showed enhanced performance and better delivery to the lower MSLI stages. The FPF increased from 15.4 ± 1.1 to 45.8 ± 0.7% when the commercial mannitol was replaced by mannitol crystallised from ethanol:water (90:10). This improvement could be due to the presence of elongated mannitol crystals in formulation blends. Solid state characterisation of engineered mannitol showed that the commercial mannitol was β-form, mannitol recrystallised from ethanol:water (85:15) was α-form and that samples recrystallised in presence of pure ethanol or other ratios of ethanol:water (95:5 and 90:10) were the mixtures of α-, β- and δ-forms. Multi-solvent recrystallisation technique was proved to have potential to produce mannitol crystals suitable for enhanced aerosolisation efficiency. Comparing different crystallised mannitol formulations showed that the final form (the type of polymorph) of the crystallised mannitol does not have a substantial effect on salbutamol sulphate aerosolisation performance.     

Influence of peak inspiratory flow rates and pressure drops on inhalation performance of dry powder inhalers

The aim of this study was to reveal the relationship between human inspiratory flow patterns and the concomitant drops in pressure in different inhalation devices, and the influence of the devices on inhalation performance. As a model formulation for inhalers, a physically mixed dry powder composed of salbutamol sulfate and coarse lactose monohydrate was selected. The drops in pressure at 28.3?L/min of three inhalation devices, Single-type, Dual-type, and Reverse-type, was 1.0, 5.1, and 8.7?kPa, respectively. Measurements of human inspiratory patterns revealed that although the least resistant device (Single) had large inter- and intra-individual variation of peak flow rate (PFR), the coefficients of variation of PFR of the three devices were almost the same. In tests with a human inspiratory flow simulator in vitro, inhalation performance was higher, but the variation in inhalation performance in the range of human flow patterns was wider, for the more resistant device. To minimize the intra- and inter-individual variation in inhalation performance for the model formulation in this study, a formulation design that allows active pharmaceutical ingredient to detach from the carrier with a lower inhalation flow rate is needed.     

Formulation optimization and in vitro antibacterial ability investigation of azithromycin loaded FDKP microspheres dry powder inhalation

Azithromycin loaded fumaryl diketopiperazine(FDKP) dry powder inhalation was designed and prepared for the treatment of community-acquired pneumonia.The solubility of FDKP and stability of azithromycin solution was investigated.Formulation of azithromycin loaded FDKP microparticle was investigated and optimized by the single factor experiment.High-pressure homogenization and spray drying conditions were also optimized to prepare the particles by spray drying azithromycin dissolved FDKP microparticle suspension at pH 4.5.The in vitro antibacterial efficiency and in vitro dispersion performance was also investigated to confirm the antibacterial efficiency,dispersion and deposition behavers.FDKP/azithromycin mass ratio(3:2) was the optimized formulation of azithromycin loaded FDKP microparticle with the maximal drug loading efficiency.High-pressure homogenization and spray drying conditions were also optimized.The in vitro antibacterial results indicated that only with the antibiotic concentration higher than mutant prevention concentration could totally inhibit the reproduction of bacteria.In vitro dispersion performance of azithromycin loaded FDKP microparticles(AZM@FDKP-MPs) also shows remarkable improvement of dispersion and deposition behavers of AZM.AZM@FDKP-MPs dry powder inhalation as a targeting delivery route has better potential for lung infection treatment.     

Influence of chemical impurities in ammonium phosphate and ammonium sulfate on the properties of ABCE fire extinguishing dry powders

The influence of chemical impurities on hygroscopic properties, as well as on the grinding and modification efficiency of ammonium phosphate and ammonium sulfate was analyzed. It was shown that application of chemically pure ammonium sulfate and ammonium phosphate free of ammonium fluoride and magnesium phosphate impurities provides the best conditions for obtaining fire extinguishing dry powders with high fire suppression ability and properties that satisfy relevant specifications.     

Influence of the relative humidity on aminosilane molecular grafting properties

Functional coatings with amino groups are used in a wide range of biochemistry-related applications. A technological platform that takes advantage of the affinity between amino-functionalized coatings and biomolecules is the DNA microarray methodology. Reliability and reproducibility of the microarray data strongly depend on the quality of the substrate; therefore, a proper awareness of how the storage conditions affect the amino-functionalized coatings is necessary. In this work we have studied the influence of different relative humidity levels on amino-methyl-silane coatings prepared via sol–gel methodology. Drops of a buffer solution containing a luminescent dye have been deposited (or spotted) on the coating; the dye molecules react with the amino-groups and leave circular luminescent marks (spots) on the substrate surface. Shape and luminescence of the spots, as well as background signals, have been monitored using a microarray laser scanner. With the proposed protocol we have measured the changes of these variables due to different storage conditions. FT-IR measurements have been performed to investigate the related chemistry changes.     

Optimization and characterization of dry powder of fanhuncaoin for inhalation based on selection of excipients

In this study, dry powder formulations for inhalation of fanhuncaoin, a newly discovered antiinflammatorily active compound isolated from Chinese herb, were designed to optimize the composition and further explore the relationship between the composition, the physical properties and the aerosolization performance. Dry powders were prepared by spray-drying using leucine, chitosan, chitosan oligosaccharide and dipalmitoyl phosphatidylcholine (DPPC) as excipients. Following spray-drying, resultant powders were characterized using scanning electron microscopy, tapped density analysis, laser diffractometry, thermogravimetric analysis and differential scanning calorimetry. The aerosol behaviour of the powders was studied in a Twin Stage Impinger at an airflow rate of 60 l/min using a HandiHaler? inhaler device. Results revealed that the nature and the relative proportion of the excipients greatly influenced the physical characteristics of the powders and their aerodynamic behavior. Among the combinations tested, the composition ratio of fanhuncaoin/leucine/chitosan/chitosan oligosaccharide/DPPC of 10/45/33.75/11.25/0.4 (w/w/w/w/w) prepared in a total solid mass of 1% (w/v) formulation was found to be particularly optimal and exhibited a tapped density of 0.44 g/cm3, an aerodynamic diameter of 2.24 μm and an respirable fraction of 51.29%. In conclusion, optimization of the aerosolization properties of inhalation dry powders could be achieved by appropriately selecting the composition of the particles.     

Effect of counterions on surface and foaming properties of dodecyl sulfate

The influence of counterions of surfactant on interfacial properties is studied by measuring foamability, foam stability, equilibrium and dynamic surface tension, and surface viscosity. The surfactant chosen is anionic dodecyl sulfate with various counterions, Li(+), Na(+), Cs(+), and Mg(++). Surface tension measurements show a decrease in the following order: LiDS > NaDS > CsDS > Mg(DS)(2). Foamability done using shaking method shows similar order as surface tension, i.e., LiDS > NaDS > CsDS > Mg(DS)(2). This has been explained in terms of the differences in micellar stability and diffusion of monomers. This is further confirmed by our dynamic surface tension results, which show the same order as equilibrium surface tension (i.e., LiDS > NaDS > CsDS > Mg(DS)(2)) at low bubble frequencies but the order is LiDS > NaDS = Mg(DS)(2) > CsDS at high bubble frequencies. Foam stability measurements were done at concentrations below and above cmc to elucidate the role of micelles. It was found that there is no significant change in foam stability when counterions are changed for surfactant concentration values below the cmc, but at concentration above cmc the foam stability of CsDS and Mg(DS)(2) are much greater than LiDS and NaDS indicating presence of stable micelles are essential to high foam stabilities. Surface viscosity measurements correlated well with the foam stability trends and gave the following order LiDS < NaDS < CsDS < Mg(DS)(2), indicating that the molecules of CsDS and Mg(DS)(2) are tightly packed at the air/water interface.     

Gravimetric characterisation of the surface properties of a porous drug carrier

The gas adsorption method is the most common means to characterise the topology of solid surfaces with regard to its use as an adsorbent. Adsorption isotherms are determined advanta-geously using a vacuum microbalance: Thermogravimetric techniques allow the observation of sample degassing and its optimization. The dry mass is determined in situ, the mass of gas adsorbed is measured directly and different gases can be used without calibration. From the isotherm the pore size distributions, specific surface area, fractal dimension and density can be derived. Commercially available gravimetric sorption apparata and vacuum balances as well as software for data evaluation are reviewed in tables. The sorption analysis of an aluminum oxide is presented. The porous material was used as a matrix for a slow drug release.     

硫酸沙丁胺醇的毛细管电泳非接触电导法检测

建立了毛细管电泳-非接触电导检测分离测定硫酸沙丁胺醇的分析方法。分别考察了分离介质、背景电解质及其浓度和pH、分离电压、进样时间、激发电压、激发频率等因素对实验结果的影响。在优化的实验条件(以15 mmol/L乳酸水溶液(pH 2.7)为电泳介质,10 kV下电动进样3 s,分离电压为10 kV,激发电压为60 V,激发频率为120 kHz)下,硫酸沙丁胺醇的检出限(信噪比为3)为1.92 mg/L,在9.60～48.0 mg/L质量浓度范围内有良好的线性关系(r=0.995),迁移时间的相对标准偏差(RSD)为2.7%。将该方法用于硫酸沙丁胺醇片和硫酸沙丁胺醇气雾剂中的硫酸沙丁胺醇含量的测定,加标回收率为90%～113%,检测结果与药厂的标示值相符合,为硫酸沙丁胺醇的检测提供了一种简便、快速、高灵敏的方法。关键词: 毛细管电泳;非接触电导检测法;硫酸沙丁胺醇;硫酸沙丁胺醇片;硫酸沙丁胺醇气雾剂     

Influence of sodium dodecyl sulfate on the physicochemical properties of whey protein-stabilized emulsions

The influence of sodium dodecyl sulfate (SDS) on the flocculation of droplets in 20 wt.% soybean oil-in-water emulsions stabilized by whey protein isolate (WPI) was investigated by light scattering, rheology and creaming measurements. The SDS concentrations used were low enough to prevent depletion flocculation by surfactant micelles and extensive protein displacement. In the absence of SDS, emulsions were prone to droplet flocculation near the isoelectric point of the proteins (4<pH<6), but were stable at a higher and lower pH. Flocculation led to an increase in emulsion viscosity, pronounced shear thinning behavior and accelerated creaming. When the surfactant-to-protein molar ratio was increased from 0 to 10, the emulsion instability range shifted to lower pH values due to binding of the negatively charged SDS molecules to the droplets. Our results indicate that the physicochemical properties of protein-stabilized emulsions can be modified by utilizing surfactant–protein interactions.