Axel Mescher

Spray Drying of Mannitol as a Drug Carrier—The Impact of Process Parameters on Product Properties

Powders intended for the use in dry powder inhalers have to fulfill specific product properties, which must be closely controlled in order to ensure reproducible and efficient dosing. Spray drying is an ideal technique for the preparation of such powders for several reasons. The aim of this work was to investigate the influence of spray-drying process parameters on relevant product properties, namely, surface topography, size, breaking strength, and polymorphism of mannitol carrier particles intended for the use in dry powder inhalers. In order to address this question, a full-factorial design with four factors at two levels was used. The four factors were feed concentration (10 and 20% [w/w]), gas heater temperature (170 and 190°C), feed rate (10 and 20 L/h), and atomizer rotation speed (6,300 and 8,100 rpm). The liquid spray was carefully analyzed to better understand the dependence of the particle size of the final product on the former droplet size. High gas heater temperatures and low feed rates, corresponding to high outlet temperatures of the dryer (96–98°C), led to smoother particles with surfaces consisting of smaller crystals compared to those achieved at low outlet temperatures (74–75°C), due to lower gas heater temperatures and higher feed rates. A high solution concentration of the feed also resulted in the formation of comparably rougher surfaces than a low feed concentration. Spray-dried particles showed a volume-weighted mean particle size of 71.4–90.0 µm and narrow particle size distributions. The mean particle size was influenced by the atomizer rotation speed and feed concentration. Higher rotation speeds and lower feed concentrations resulted in smaller particles. Breaking strength of the dried particles was significantly influenced by gas heater temperature and feed rate. High gas heater temperatures increased the breaking strength, whereas high feed rates decreased it. No influence of the process parameters on the polymorphism was observed. All products were crystalline, consisting of at least 96.9% of mannitol crystal modification I.

Impact of excipients on coating efficiency in dry powder coating.

Dry powder coating is a technique to coat substrates without the use of organic solvent or water. The polymer powder is directly applied to the cores to be coated. Liquid additives are often used to lower the glass transition temperature of the polymer and to enhance the adhesion of the powder to the cores. This leads to an increase in coating efficiency of the process. The impact of various liquid additives and their properties like spreading behavior, viscosity and plasticizing activity were investigated with respect to their influence on the coating efficiency of the process. Ethylcellulose and hydroxypropyl methylcellulose acetate succinate were used as coating polymers. Spreading behavior of the liquid additive on the polymer was the most influencing parameter and could be successfully predicted with contact angle measurements on polymer films. Calculations of works of adhesion and spreading coefficients also revealed to be promising predictive techniques for choosing suitable additives to improve process efficiency. Isopropyl myristate showed the best spreading behavior resulting in the highest coating efficiency. Based on these results, a formulation for ethylcellulose containing isopropyl myristate was developed and film formation was examined using dissolution testing and imaging techniques to evaluate the optimum curing conditions.

Spray Drying Tailored Mannitol Carrier Particles for Dry Powder Inhalation with Differently Shaped Active Pharmaceutical Ingredients

Dry powder inhalation as commonly used in the local therapy of asthma or chronic obstructive pulmonary disease (COPD) is a very effective route of drug delivery. The system of small cohesive drug particles attached to the surface of large carriers with particle sizes >50 μm is successfully applied to numerous marketed products. The performance of these blends is based on the particle properties of both carriers and drug particles and is usually linked to the Fine Particle Fraction (FPF), which represents the fraction of drug particles with an aerodynamic diameter of 1–5 μm, which triggers the desired effect in the lung. Mannitol, which was chosen as an alternative carrier to the market-leading α-lactose monohydrate as it is highly crystalline in contrast to lactose even after spray drying, was prepared by spray drying to generate carrier particles at a range of 50–90 μm with various morphologies. This project was first aiming at the examination of the drying kinetics of bicomponent mannitol water droplets. It could be shown that high drying temperatures cause deep indentations and increasingly rough surface structures, while low drying temperatures result in spherical particles with rough surfaces at very low drying temperatures and smoother ones when increasing temperatures. Low rotation speeds and high mass fractions increase the particle size. Further particle properties like porosity, breaking strength or flowability were related accordingly. A defined set of mannitol batches was further selected for interactive powder blends with a micronised and spray dried quality of the model drug SBS. Particle–particle interactions were then investigated by correlating carrier properties to the resulting FPF. Particle shape was found to hinder the detachment of drug particles. Rough structures dried at the lowest drying temperatures were preferred for micronised drug particles, whereas spherical drug particles were preferably detached from smoother surfaces. This effect could be related to the drug size as only the detachment of the smallest drug particles (<1 μm) tended to be affected by the roughness. Carrier size was found to decrease the FPF for larger particles, when indentations occur simultaneously. Thus, it was possible to customise the carrier properties according to the drug particle properties to finally obtain adhesive drug–carrier mixtures with optimum aerodynamic performance.

Experimental Evaluation and Control of Interaction of Gas Environment and Rotary Atomized Spray for Production of Narrow Particle Size Distribution

The production of particles with a narrow particle size distribution by spray drying is a demanding challenge in industrial application. The laminar thread breakup is one option as employed by an innovative rotary spraying device (Schroder and Walzel, Chemical Engineering and Technology 21: 349–354, 1998; Erzeugung und Zerfall gedehnter Laminarstrahlen im Schwerefeld, Aachen, 2002; Designing thread forming rotary atomizers by similarity trials, 2012; Einfluss der Gasfuhrung in Spruhtrocknern auf den Fadenzerfall an Rotationszerstaubern—Analyse und Optimierung, Munchen, 2012). The feed enters the rotary wheel from the top and flows through the device as laminar open channel flow. It leaves the cup through bores and single laminar threads are obtained upon detachment. These threads ideally break up driven by surface tension. In spray experiments, a broader drop size distribution is observed than expected from theory. Within the presented work, the effect of a relative velocity between the thread the ambient gas on the laminar thread breakup is identified and addressed as mayor factor (Mescher et al., Chemical Engineering Science 69:181–192, 2012).