High dose pulmonary delivery – Evaluation of force control agents in Softpellets

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Summary

The expanding application of Dry Powder Inhalers (DPIs) in the treatment of lung infections and cystic fibrosis has led to development of new techniques for high dose respiratory drug delivery. The formation of softpellets is a simple and low-cost method to obtain good flowable preparations from micronised powders that are easy to handle. In this study, a new continuous manufacturing method with a vibrating chute was used, in which a further classification of the product is not necessary. The size of the resulting softpellets can be determined by selecting the mesh size of the sieve used for pre-agglomeration. Furthermore, the particle size and span value is influenced by how often the product slides down the chute. After pre-agglomeration with a 500 µm sieve, the softpellet sizes ranged between 414.55 µm ± 15.55 µm (Span: 0.68) and 460.50 µm ± 10.05 µm (Span: 0.73) after three times of sliding and between 274.96 µm ± 8.37 µm (Span: 0.98) and 370.50 ± 10.02 (Span: 0.81) after six times of sliding down the chute. With these particle sizes, a conventional capsule based inhaler that punctures the capsule is unsuitable as contained softpellets would not be released. Therefore, it was investigated whether the Twister from Aptar, an inhaler that opens the capsule, can be used to disperse these formulations. Softpellets made of pure rifampicin as model drug showed a Fine Particle Fraction (FPF) of up to 54.46 % ± 2.42 % with this device. By adding 5 % magnesium stearate (MgSt), a FPF of up to 59.21 % ± 2.86 % can be obtained. The addition of 5 % lactose to the softpellets even achieved an FPF of 61.34 ± 1.17 %.

 

Key Message

In this study API soft powder agglomerates were produced utilising a continuous method based on vibration. To improve the deagglomeration behaviour while inhalation the suitability of magnesium stearate and fine lactose were investigated as possible force control agents in rifampicin softpellets.