Nanosized rods agglomerates as a new approach for formulation of a dry powder inhaler

Abstract

Background: Nanosized dry powder inhalers provide higher stability for poorly water-soluble drugs as compared with liquid formulations. However, the respirable particles must have a diameter of 1–5 μm in order to deposit in the lungs. Controlled agglomeration of the nanoparticles increases their geometric particle size so they can deposit easily in the lungs. In the lungs, they fall apart to reform nanoparticles, thus enhancing the dissolution rate of the drugs. Theophylline is a bronchodilator with poor solubility in water. Methods: Nanosized theophylline colloids were formed using an amphiphilic surfactant and destabilized using dilute sodium chloride solutions to form the agglomerates. Results: The theophylline nanoparticles thus obtained had an average particle size of 290 nm and a zeta potential of −39.5 mV, whereas the agglomerates were 2.47 μm in size with a zeta potential of −28.9 mV. The release profile was found to follow first-order kinetics (r 2 > 0.96). The aerodynamic characteristics of the agglomerated nanoparticles were determined using a cascade impactor. The behavior of the agglomerate was significantly better than unprocessed raw theophylline powder. In addition, the nanoparticles and agglomerates resulted in a significant improvement in the dissolution of theophylline. Conclusion: The results obtained lend support to the hypothesis that controlled agglomeration strategies provide an efficient approach for the delivery of poorly water-soluble drugs into the lungs.

Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

“…Conversion of nanosuspensions to micron-sized nanoparticle assemblies with suitable aerodynamic properties can be used as a platform for the delivery of poorly watersoluble drugs to the lungs using DPIs. This platform, after suitable modifications, can also benefit the aerosolisation of water-soluble drugs [94,95]. Spray drying and the aerosol flow reactor have been successfully applied for the production of inhalable nanoparticle agglomerates with enhanced dissolution and aerosolisation efficiency.…”

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

“…There are few published studies on engineering inhalable theophylline particles. A low-dose pressurised metered-dose inhaler (pMDI) formulation of theophylline (Zhu et al, 2015a) and formulations for dry powder inhalers (polymeric composite particles, microspheres, cocrystals and nanosized rods agglomerates) have been produced and characterised (Alhalaweh et al, 2013;Kadota et al, 2015;Momeni and Mohammadi, 2009;Salem et al, 2011;Zhang et al, 2009;Zhu et al, 2015b). Blends of theophylline microparticles (63-90 μm) with inhalable budesonide and terbutaline particles (< 5 μm) were proposed as a formulation approach for concurrent oral and pulmonary drug delivery with theophylline acting as a carrier (Salama et al, 2014).…”

Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration

“…5 However, respirable particles must have a diameter of 1-5 µm in order to deposit in the lungs. 6 Nanosuspensions have been employed to enhance the dissolution rate of poor water-soluble drugs. 7 Techniques used to produce drug nanosuspensions can be divided into two major classes: top-down and bottom-up technologies.…”