Design and development of a disposable high dose dry powder inhaler for aminoglycosides

M. Hoppentocht, P. Hagedoorn, H.W. Frijlink, A.H. de Boer

Background: Currently applied nebulisation techniques for the administration of antibiotics to patients are time consuming and expensive and therefore, inappropriate for antibiotic therapies against infectious diseases like tuberculosis in developing countries. Dry powder inhalers may be an interesting alternative as they can be simple, cheap and thus, disposable which is an advantage for pulmonary antibiotic delivery. To become successful, it requires that the use of excipients is minimised and that simple production techniques are applied.
Methods: For high dose drug formulations without excipients it is required to adapt the design of the dry powder inhaler to the specific properties of the drug, which for aminoglycosides are troublesome in relation to dispersion and inhaler retention. We modified the TwincerTM for delivery of tobramycin as model compound for aminoglycosides and investigated dispersion efficiency of a spray dried product with laser diffraction technique and the inhaler retention by gravimetrical analysis.
Results: In the re-designed TwincerTM, the fine particle fraction smaller than 5 μm was 75% at 2 kPa and more than 80% at 4 and 6 kPa. The inhaler retention decreased to less than 15% at all three pressure drops.
Conclusion: The TwincerTM dry powder inhaler can be optimised for spray-dried tobramycin base by re-designing the classifiers and changing the flow breakdown. This new concept is called ‘Cyclops’ and has a single classifier with more air inlet channels compared to the two parallel classifiers of the basic TwincerTM.

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