(195e) Dispersion of Surface Modified Powders for Inhalation Application

Active pharmaceutical ingredients used in the inhaler application have aerodynamic diameters typically in the size range of 2 ~ 5µm. Such powders are extremely cohesive due to strong Vander Waal's forces and very difficult to flow, thus create severe problems for the effective dispersion for the treatment of respiratory diseases. In addition, the drug dosage uniformity is also a critical issue because of the formation of agglomerates. Excipients such as monohydrate lactose are commonly employed, which act as drug carriers in these applications. Understanding of interaction of drug particles with excipients is very important for the effective performance and depends on various parameters such as blending procedures, application of high/low shear, particle size distribution, properties of materials, etc. In this work, various tools to improve flow of powders through surface modification methods, which may be dry coating of original poorly flowing powders with nano silica (physically altering the surface structure), surface treatment (chemically altering the surface structure) or continuous grinding and coating techniques are presented. Specifically, application of a low shear and high shear blending using a hybridization system (Nara machineries Ltd.) is discussed to investigate the particle size reduction of the carrier lactose particles. The effect of various rotational speeds and the duration of processing time are investigated. In order to increase the dispersion and dissolution of drugs while maintaining the flowability of drugs, nano-size guest particles are coated on the surface of drugs (host particles) through a novel approach of simultaneous size reduction and surface modification by using Fluid Energy mill (FEM). The novelty of the method lies in the simultaneous coating and size reduction and use of hydrophobic as well as hydrophilic materials for surface modification. Various Sympatec dispersion instruments, including the Rodos and the Inhaler are utilized for careful characterization of the particle size as well as dispersibility of the surface modified particles. It is found that powders in size range 1-10 microns are produced with high API content (>95 %), having good dispersion and flowability, suitable for the inhaler application.