Applied Solutions to Overcome the Challenge of Dosing Particle-Engineered Powders

Particle-engineering is more and more applied to dry powder inhaler (DPI), particularly spray drying due to its versatility. However, the extra small particle size (d50 ≤ 3 µm) which determines a high bulk cohesiveness and adhesiveness of these powders and, therefore, very poor flow properties, does not enable for reproducible and accurate powder filling into capsules, reservoir, or any primary packaging container for delivery by an inhaler. In addition, the general low density and moisture sensitivity of spray dried powders makes powder handling even more challenging and increases the risk of failure if standard commercial processes developed for carrier-based DPI are directly applied to these engineered powders with the risk of delays and unexpected cost during product development. Whereas it is important to test powder processing since early stages of development, different solutions can be implemented when handling particle-engineered challenging powders. All these approaches will be described and discussed during the presentation, showing several real-life examples.

A great challenge when handling pure micronized powders is their cohesion/adhesion behavior which ultimately results in poor flow, high relative standard deviation (RSD) of fill weight and very poor content uniformity of the product filled into the primary packing container (i.e. capsules). The different approaches that can be employed to overcome this challenge are: mechanical solutions applied to the filling equipment or they can be focused on improving the flow properties of spray dried powders. Whereas conventional methods, like wet and dry granulation, are quite impractical for DPI, the process of creating soft-pellets has been used to improve powder flow properties and, consequently, handling. The effect of employing soft-pellets to facilitate dosing of spray dried powders will be illustrated through some real-case examples on how and when it can be employed. Furthermore, an alternative to obtain a product to process with better handling properties can be to blend the pure micronized powder with a carrier. Other examples on this approach will be discussed together with its advantages and limitations.

If we focus instead on what can be mechanically implemented on the filling equipment to obtain a homogenous and reproducible powder dosing of engineered pure micronized powders, the two approaches that can be applied are sonication in the dosing hopper or inline sieving in the feeding hopper. Sonication can be used, alongside stirring, to improve pure micronized powder feeding. It can be ideal for certain type of powders, but it presents some limitations when applied to low density powders and it might not be indicated for sensitive active ingredients (i.e. certain class of biologics or nanocomposite microparticles). For this reason, inline sieving of the powder in the feeding hopper represents a much more suitable solution. This has been used with various DPI products: from low density engineered powders for a more efficient lung delivery to nano-in-micro powder for the delivery of a peptide to the heart. These examples will be illustrated in the presentation, to show how to achieve a homogenous (content uniformity > 90%) and reproducible (RSD ≤ 2%) dosing of particle-engineered powders.