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.
Dry powder inhalations are employed for the delivery of drugs to the lungs for the treatment of pulmonary and systemic diseases. It has been reported that in aerosol inhalation therapy, the effect of a drug on respiratory diseases is closely related to the aerodynamic diameter of the inhaled drug particles.1) For the treatment of asthma and alveobroncholitis, in particular, drug particles with an aerodynamic diameter of 1-6 mm are most effective.2) Thus dry powder inhalations are formulated with micronized drug particles. However, micronized drug particles are very adhesive and cohesive with poor flow properties, and cause problems in packing micronized drug particles into capsules and inhalation devices.To solve these problems, a coarse carrier particle system in which drug particles are physically mixed with coarse carrier particles such as lactose is commonly used. Carrier particles are used to improve the flow of fine drug particles or to obtain uniform filling of fine drug particles into inhalation devices and capsules. Carrier particles also decrease the residual fine drug particles that adhere to inhalation devices and capsules upon inhalation of fine drug particles. With the use of carrier particles, drug particles are emitted from capsules and devices more easily, and the inhalation efficiency increases. Therefore both the design of the carrier particle and the design of drug particles are important for the development of dry powder inhalations. In the design of dry powder inhalations with carrier particles, it is important to consider how to obtain good flow, the packing properties of the drug/carrier powder mixture, and how to obtain a good outflow from capsules and devices. Therefore the evaluation of the flow and packing properties of dry powder inhalations are necessary. However, only a few studies reported on comparison of mechanical properties such as the flow and packing properties with the inhalation properties in dry powder inhalations using carrier particles. 3)For dry powder inhalations with carrier particles, first, reliable emission of the drug adhering to carrier particles from the capsule and inhalation device, and second, easy separation of drug particles from the carrier emitted are important. Thus it is important to consider these inhalation processes of drug/carrier mixture in designing dry powder inhalations using carrier particles. In this study, the effects of the flow and packing properties of the drug/carrier powder mixture on the emission of drug adhering to carrier particles from capsules and inhalation devices are investigated.Otsuka et al. 4) reported that the effect of particle shape and surface asperity on the adhesive force between surfacetreated particles and a glass substrate was investigated by the impact separation method. The surface-treated particles were prepared to dissolve the protuberances on the particle surface. For this purpose, carrier particles with different particle shapes are prepared by treating the surface of lactose carrier particles. Our purpose was ...
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.
The influence of storage humidity on the in vitro inhalation properties of salbutamol sulfate dry powder with surface covered lactose carrier was investigated. In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with different particle surface conditions prepared by surface covering. Lactose carrier surfaces were covered with vegetable magnesium stearate (Mg-St-V) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer ® ). 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 covered lactose carrier were little decreased with increased in relative humidity (RH), showing that the in vitro inhalation properties of salbutamol sulfate were improved at high RH. Using this surface covering technique would thus be valuable for storage humidity of dry powder inhalation (DPI) with lactose carrier particles.Key words dry powder inhalation; storage humidity; salbutamol sulfate; lactose carrier particle; vegetable magnesium stearate 444 Notes Chem.
In designing dry powder inhalation (DPI), a pharmaceutical technique utilizing inactive and coarse carrier particles such as lactose is applied to improve inhalation properties of micronized drug particles with aerodynamic particle diameters of 1-6 mm.1-6) During inhalation, carrier particles help the emission of the drug from the device or capsules and improves its inhalation properties. Therefore, in designing a DPI using carrier particles, it is important for drug particles to be adequately separated from the surface of carrier particles for inhalation. The in vitro inhalation properties of DPI are reported to be related to the surface properties of the carrier particles.2,7-9) We previously reported the effects of a lactose carrier prepared by dissolving the surface of lactose particles with a water solution of ethanol (70 v/v %) on in vitro inhalation properties. 7) In this study, we layered the surface of lactose particles with magnesium stearate in a dry condition. This technique is advantageous for the safety and environmental protection because of elimination of the possibility of residual solvent and the need to dispose of the waste fluid containing the solvent by the disuse of an organic solvent in the surface-layering process. We previously reported effects of a lactose carrier surface-layered with magnesium stearate on in vitro inhalation properties of salbutamol sulfate.10) There has since been no other report on the use of lactose surface-layered with magnesium stearate as a carrier. Therefore, we layered the surface of coarse lactose particles, which have been used as an inhalation carrier, with vegetable magnesium stearate, which is widely used as a lubricant in the pharmaceutical field. Recently, in the field of pharmaceutics, there is a trend to limit the use of animal-derived excipients with preference to substitute them with vegetable excipients. We, therefore, carried out basic investigations on the effects of surface layering time of lactose carrier particles with vegetable magnesium stearate on DPI of salbutamol sulfate. ExperimentalPowder Samples As the carrier particle for dry powder inhalation, alactose monohydrate was used (Pharmatose ® 200M, DMV, The Netherlands). Salbutamol sulfate was used as the drug, and was obtained from LEIRAS (Finland). Salbutamol sulfate was micronized by Spiral Jet Mill (100AS, Hosokawa Micron, Japan). The cube-like fine crystals of the latter had a volume median diameter of 1.7 mm, as determined by laser diffraction (Lasermicronsizer, SEISHIN, Japan). Vegetable magnesium stearate (Mg-St-V) with mean diameter of 3.3 mm was obtained from Taihei Chemical (Japan).Physical Properties of Lactose Carrier Particles The mean particle diameter (Heywood diameter) of lactose particles was determined using an image analyzer (Luzex-FS, NIRECO, Japan) connected to a microscope (OPTIPHOT, Nikon, Japan). The specific surface area of lactose particles was measured by an air permeametry method (SS-100, Shimadzu, Japan). The surface condition of lactose particle was observed b...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.