[Efficiency improvement of fluticasone propionate dry powder formulation for inhalation in pulmonary patients]

Background: Nowadays, inhaled corticosteroids have become the core of therapy for patients with asthma and chronic obstructive pulmonary disease [COPD]. Fluticasone propionate [FP] is among the most lipophilic steroids [water solubility 0.1 mg/ml] and its clinical efficacy has been confirmed in many studies .The inclusion of different carrier materials in a dry powder inhaler [DPI] system can alter formulation performance, which might be attributable to variation in the adhesion between drug and carrier particles.

Materials and methods: To this aim, we used two different carriers to be mixed in different times with drug on the one hand to facilitate the powder flow during manufacturing, and on the other hand to help fluidization upon patient inhalation. The prepared DPI formulations were examined in terms of drug content uniformity upon the physical blending, particle shape, and in vitro pulmonary deposition. The latter was determined using an Andersen cascade impactor and Cyclohaler® as a single-dose DPI

Results: Our results revealed that the highest fine particle fraction [FPF] and fine particle dose [FPD] value belonged to the formulation contained FP: mannitol, mixed in 30 minutes

Conclusion: It can be concluded that using mannitol as the coarse carrier can improve the physical properties as well as the aerosolization behavior of the resultant DPI formulations

Preparation and characterization of rifampin loaded mesoporous silica nanoparticles as a potential system for pulmonary drug delivery

The goal of this research is to determine the feasibility of loading rifampin into mesoporous silica nanoparticles. Rifampin was selected as a model lipophilic molecule since it is a well-documented and much used anti tuberculosis drug. The mesoporous silica nanoparticles were prepared by using tetraethyl ortho silicate and cetyltrimethyl ammonium bromide [as surfactant]. The prepared nanoparticles were characterized in terms of their particle size measurement and porosimetry. The results showed that the particle size is 218 +/- 46 nm [mean +/- SD] and surface area is 816 m[2]g[-1]. In order to load rifampin within the mesopores, adsorption experiments using three different solvents [methanol, water and dimethyl sulfoxide] were carried out. The loading procedure resulted in a significant improvement in the amount of rifampin loaded into mesoporous silica nanoparticles and methanol was found to be a suitable solvent, providing a drug entrapment efficiency of 52 %. Rifampin loaded nanoparticles underwent different in-vitro tests including, SEM and drug release. The in-vitro drug release was investigated using buffer phosphate [pH=7.4]. Regarding the drug release study, a biphasic pattern of release was observed. The drug-loaded mesoporous silica nanoparticles were capable of releasing 95% of their drug content after 24 h, following a faster release in the first four hours. The prepared rifampin loaded nanoparticles seem to have potential for use as a pulmonary drug delivery

Preparation and in-vitro evaluation of rifampin-loaded mesoporous silica nanoaggregates by an experimental design

The goal of this research is preparation, optimization and in-vitro evaluation of rifampinloaded silica nanoparticles in order to use in the pulmonary drug delivery. Nanoparticles are exhaled because of their small size. Preparation of nanoaggregates in a micron-size scale and re-dispersion of them after deposition in the lung is an approach to overcome this problem. We used this approach in our research. Rifampin was selected as a model lipophilic molecule since it was a well-documented and much used anti tuberculosis drug. A half factorial design was used to identify significant parameters of the spray drying process. The results showed that feed concentration, feed pH and the interaction between feed flow rate and gas atomizer flow rate had statistically significant effects on the particle size of nanoaggregates. The Box-Behnken design was employed to optimize the spray drying process. Finally, a quadratic equation which explains the relation between independent variables and aerodynamic diameter of nanoaggregates was obtained. Rifampin-loaded silica nanoaggregates underwent different in-vitro tests including: SEM, Aerosol performance and drug release. The in-vitro drug release was investigated with buffer phosphate [pH=7.4]. Regarding the drug release study, a triphasic pattern of release was observed. The rifampin-loaded silica nanoaggregates were capable of releasing 90% drug content after 24 h in combination patterns of release. The prepared rifampin-loaded nanoaggregates seem to have a potential to be used in a pulmonary drug delivery

Influence of formulation variables and inhalation device on the deposition profiles of cromolyn sodium dry powder areosols

Dry powder inhalers [DPIs] have attained considerable attention due to their propellant-free formulations and the patient's inherent coordination with actuation. Generally, DPI formulations consist of a micronized drug alone or mixed with carrier particles. This study was carried out to investigate the effects of carrier particle size and weight fraction on aerosolisation behaviour of cromolyn sodium [CS]. Pharmatose[R] 450M and Pharmatose[R] 325M, two commercial alpha -lactose monohydrate with different particle sizes, were blended in two different fractions [30 and 50% w/w] with CS. A low resistance device [Spinhaler[R]] and a medium resistance device [Cyclohaler[R]], were used to evaluate the effect of inhaler design on the deposition profiles of CS. The in vitro deposition of the formulations was determined using a twin stage impinger [TSI]. Fine particle dose, fine particle fraction and emitted dose of the drug were depended to both formulation and inhalation devices. Fine particle fractions of the drug aerosolised from the formulations ranged from 9.35 up to 36.45%. The highest fine particle fraction was produced by formulation containing 50% Pharmatose[R] 450M as carrier. Cyclohaler[R] showed higher efficiency in aerosolisation of CS compared to Spinhaler[R]

Design and evaluation of a new dry powder inhaler.

Three versions of a new dry powder inhaler [DPI], RG-haler, were designed using two kinds of grid inserts. Salbutamol sulfate/lactose blend [Ventolin Rotacaps[R]] was selected as a model formulation to analyze the performance of all inhalers and compare their efficiency with three marketed devices [Rotahaler[R], Spinhaler[R] and ISF inhalator[R]] using the twin impinger [TI]. Deposition of the drug in device was significantly [P<0.05] lower for ISF inhalator[R] and all kinds of RG-halers in comparison with those of Rotahaler[R] and Spinhaler[R]. The amount of drug deposited in the stage 2 and the respirable dose for RG-halers were similar to those of ISF inhalator[R] and significantly [P<0.05] higher than those of Rotahaler[R] and Spinhaler[R]. The results suggest efficient aerosol generating capability of the RG-haler